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PARKINSON'S | +50 articles

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Radical Parkinson's treatment tested in patients

by Alex Therrien | 27 February 2019

A radical Parkinson's treatment that delivers a drug directly to the brain has been tested in people.

Patients in the trial were either given the drug, which is administered via a "port" in the side of the head, or a dummy treatment (placebo).

Both groups showed improved symptoms, meaning it was not clear if the drug was responsible for the benefits.

However, scans did find visual evidence of improvements to affected areas of the brain in those given the drug.

The study's authors say it hints at the possibility of "reawakening" brain cells damaged by the condition.

Other experts, though, say it is too early to know whether this finding might result in improvements in Parkinson's symptoms.

Researchers believe the port implant could also be used to administer chemotherapy to those with brain tumours or to test new drugs for Alzheimer's and stroke patients.

Parkinson's causes parts of the brain to become progressively damaged, resulting in a range of symptoms, such as involuntary shaking and stiff, inflexible muscles.

About 145,000 people in the UK have been diagnosed with the degenerative condition, which cannot be slowed down or reversed.

For this new study, scientists gave patients an experimental treatment called glial cell line-derived neurotrophic factor (GDNF), in the hope it could regenerate dying brain cells and even reverse the condition.

Participants underwent robot-assisted surgery to have four tubes placed into their brains, which allowed GDNF to be infused directly to the affected areas with pinpoint accuracy, via a port in their head.

After an initial safety study of six people, 35 patients took part in a nine-month "blinded" trial, where half were randomly assigned to receive monthly infusions of GDNF and the other half dummy infusions.

Dr Alan Whone, principal investigator, said patients in the trial had, on average, been diagnosed eight years previously, but brain scans of those given the drug showed images that would be expected just two years after diagnosis.

"We've shown with the PET [positron emission tomography] scans that, having arrived, the drug then engages with its target, dopamine nerve endings, and appears to help damaged cells regenerate or have a biological response," he said.

Tom Phipps, 63, from Bristol, said he had noticed an improvement during the trial and had been able to reduce the drugs he takes for his condition.

Since it ended, he has slowly increased his medication but is continuing to ride his bike, dig his allotment and chair his local branch of Parkinson's UK.

"My outcome was as positive as I could have wished for," he said. "I feel the trial brought me some time and has delayed the progress of my condition. The best part was absolutely being part of a group of people who've got a similar goal - not only the team of consultants and nurses but also the participants. You can't have expectations - you can only have hope."

Following the initial nine months on GDNF or placebo, all participants had the opportunity to receive GDNF for a further nine months.

By 18 months, when all participants had received GDNF, both groups showed moderate to large improvements in symptoms compared with their scores before they started the study.

https://www.bbc.com/news/health-47370498
 
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Can cannabis prevent Dyskinesia in long-term treatment of Parkinson’s Disease?

Psychedelic Times | Feb 24, 2017

In 1970, Oliver Sacks wrote five letters to various medical journals in the U.S. expressing his concern about the prescription drug levodopa, which had been developed just a year earlier. As a practicing neurologist, he had used levodopa (L-Dopa) to treat Parkinson’s and encephalitis lethargica (or “sleepy-sickness”) in his patients—both neurological disorders that arise from a deficiency of dopamine—and found it to have serious adverse effects. As he described in his 1985 book The Man Who Mistook His Wife for a Hat, treating people with sleepy-sickness with L-Dopa resulted in an over-correction of motor function: “First they were ‘awakened’ from stupor to health: then they were driven towards the other pole—of tics and frenzy.”

This phenomenon would come to be known as levodopa-induced dyskinesia—an increase in involuntary muscle movements or spasms that results from too much dopamine flooding your brain. It’s one of the most common side effects of conventional treatment of Parkinson’s Disease (PD) and one of the most devastating: some PD patients describe their dyskinesia as worse than the disease itself, causing many to decrease or put off treatment altogether to stave off the inevitable side effects.

The search for a better treatment has pointed more and more researchers toward cannabis because it naturally targets multiple points in the endocannabinoid system, the brain’s neurological center for motor function, mood, and pleasure. Marijuana has been shown to have impressive results in the short term treatment of PD symptoms, like tremors and rigidity, and it also has supplemental therapeutic effects—like easing depression and improving sleep. But perhaps most importantly, cannabis has shown promising results in preventing dyskinesia.

What Is Levodopa-induced Dyskinesia?

Because Parkinson’s is classically defined as a dopamine deficiency—caused by the death of dopamine-producing cells in a part of the brain called the substantia nigra—it’s most commonly treated with a dopamine precursor like levodopa, which then converts to dopamine in the brain. The effects from initial doses of levodopa are quite immediate—people’s motor functions are restored almost miraculously in some cases—but experience shows that long-term dopamine-based treatment can actually cause an increase in dyskinesia.

The problem arises from dopamine’s role as a neurotransmitter and the tricky balance of the neurons in your brain. In a healthy brain, dopamine transmits signals between brain cells about motor function, mood, and behavior, among other things. But in the Parkinsonian brain, low levels of dopamine mean two parts of the brain related to motor function—the endocannabinoid system and basal signia—are not signaling correctly. This is what causes the most well-known symptoms of Parkinson’s: body rigidity, tremors, and involuntary muscle contractions.

Supplementing dopamine with a drug like levodopa attempts to restore the neurological balance, but history shows the solution isn’t perfect because long-term treatment often results in dopamine hyperactivity, which manifests as dyskinesia. This most often affects younger people with PD, which is particularly disconcerting because they have longer to live with the disease and the side effects of treatment.

Cannabinoids and Parkinson’s

Almost fifty years after Sacks wrote his letters of warning, levodopa is still the most commonly prescribed treatment for Parkinson’s Disease, but the medical community is calling for a more sophisticated medicine that mirrors the function of the lost dopamine cells in the brain. And that leads us to cannabis.

Cannabis has shown tremendous promise in treating PD, both in the laboratory and in practice. A 2004 survey of 339 PD patients showed that smoking cannabis significantly improved symptoms in 46% of participants, including reduced tremors, rigidity, bradykinesia, and dyskinesia. Cannabis has also shown to decrease dystonia, another type of repetitive or twisting movement caused by involuntary muscle contractions.

A look into the relationship between cannabinoids and motor functions show why marijuana is an ideal target for the treatment of motor disorders:

Cannabis activates the endocannabinoid system, which affects motor function, mood, and pleasure. With 113 cannabinoids and counting, cannabis activates parts of the brain that dopamine treatment alone does not. In particular, cannabis activates CB1 receptors in high concentrations in three parts of the brain associated with dyskinesia and Parkinson’s: the globus pallidus, basal ganglia, and substantia nigra. This is important because, as studies have shown, activation of CB1 receptors—which comes from ingesting the marijuana cannabinoid THC—offers neuroprotection and prevents the development of dyskinesia in mice.

Cannabis increases more than just dopamine—it affects other neurotransmitters, too. Historically, Parkinson’s has been understood as a simple case of dopamine deficiency, but recent research from Harvard University suggests that dopamine neurons also transmit GABA, a neurotransmitter that dampens the effect of dopamine. This means that when neurons die in the course of the disease, there would also be a GABA deficiency. Because GABA plays an important role in dampening the effect of dopamine by inhibiting the electrical activity of cells, its decrease in PD would help explain why isolated dopamine treatment sometimes results in dyskinesia.

Conversely, it makes sense then, that a treatment that also increases GABA would inhibit dopamine hyperactivity and so dampen the extreme effects of dyskinesia. The research on cannabis in that area is promising: one study on the synthetic cannabinoid nabilone showed that it decreased the incidence of levodopa-induced dyskinesia, noting that the cannabinoids “enhance GABA transmission and may thus alleviate dyskinesia.” The study went on to suggest that this might be because cannabinoids interact with the globus pallidus, which is thought to be overactive in cases of dyskinesia.

Cannabis treats other common symptoms of Parkinson’s. There are other benefits to cannabinoids in addition to their effect on motor dysfunction. Thanks to their anti-oxidative and anti-inflammatory effects, cannabinoids are also neuroprotective, meaning they help protect against further degeneration of precious neurons. Cannabinoids have also been shown to relieve pain, have antidepressant effects, and improve sleep—all problems PD patients commonly face.

The trick of treating neurological diseases

In the end, Parkinson’s cannot be summed up simply as a deficiency of dopamine, and Oliver Sacks would agree. “There are also much subtler and more widespread changes,” he concluded in his book. “There are countless subtle paths of abnormality which differ from patient to patient, and from day to day in any one patient.”

That’s to say, neurological diseases are notoriously tricky beasts, with varying symptoms from day to day—what works for one person may not for another. There probably will never be a one-size-fits-all solution for Parkinson’s Disease, but diversifying our arsenal of medicines and continuing studies on medical marijuana can only lead to better long-term treatment without debilitating side effects. With further research and continuing legalization measures, cannabis could become the long-term dyskinesia treatment so many PD patients are looking for.

https://psychedelictimes.com/2017/0...in-long-term-treatment-of-parkinsons-disease/
 
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Studies highlight the protective effects of caffeine in Parkinson’s

Marisa Wexlerby | March 28, 2019

Two new studies in mice suggest that caffeine might have protective effects in the brains of Parkinson’s disease patients.

The studies will be presented during the 14th International Conference on Alzheimer’s and Parkinson’s Diseases and related neurological disorders, March 26-31 in Lisbon, Portugal.

Previous epidemiological studies have suggested that consuming caffeine might protect against the development of Parkinson’s. These more-recent studies set out to test this premise more directly in an animal model.

Both studies used mouse models of Parkinson’s that involved injecting mice with alpha-synuclein. This protein is a major component of Lewy bodies, irregular “clumps” in brain cells that are a hallmark of Parkinson’s pathology. Specifically, both research teams used a mutant form of the protein called A53T, which forms these clumps even more effectively than the wild-type protein.

In both studies, injection with A53T led to changes characteristic of Parkinson’s disease, such as impaired motor function and memory, as well as changes in brain physiology, like the development of the aforementioned Lewy bodies and loss of dendritic spines (parts of neurons involved in making connections in the brain).

However, when the mice were given caffeine in their drinking water, these effects were lessened. Both studies showed similarly beneficial results, though the exact parameters that were measured were different.

In the first study, researchers at Aarhus University, Denmark, report that mice given caffeine had less alpha-synuclein in their brains. Caffeine also caused a three–week delay in the onset of clasping, which is a behavior mice do with their hind limbs that is indicative of brain damage. Furthermore, caffeine-treated mice lived, on average, 40% longer than their counterparts who weren’t given caffeine.

In the second study, researchers at Wenzhou Medical University, China, reported that mice given caffeine had fewer memory problems and more dendritic spines than their untreated counterparts.

Both studies support the previous epidemiological evidence that caffeine can be protective for Parkinson’s disease, although there is the usual caveat that experiments in animal models are never a perfect replica of actual human disease.

It also is not clear why or how caffeine might have such protective effects, and further research will be needed to figure out just how caffeine might benefit Parkinson’s patients.

https://parkinsonsnewstoday.com/201...ve-effects-of-caffeine-in-parkinsons-disease/
 
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Vitamin B12 found to inhibit a key enzyme in hereditary Parkinson’s disease

Neuroscience News | April 4, 2019

Vitamin B12 significantly prevents the neurotoxicity of LRRK2 genetic variants associated with hereditary Parkinson’s disease. The findings may help with the development of new therapies to combat the neurodegenerative disease.

Parkinson’s is the most common, chronic neurodegenerative movement disorder affecting 1% of the global population over seventy years of age. Right now, there is no cure for this disease and the available treatments focus on addressing its symptoms but not its progression.

Although most cases of Parkinson’s are sporadic, the inheritable variants of the disease are mainly associated with mutations of the gene that encodes the LRRK2 enzyme. In 2004 an international research team, in which researchers from the Basque Country participated, established the link between one of the mutations in this enzyme and patients diagnosed with the disease.

So the LRRK2 enzyme, which is also known internationally by the name “dardarina”, the Basque word that means tremor, has become one of the most attractive therapeutic targets for developing new drugs to combat inheritable Parkinson’s. Neurotoxicity, or the pathogenic effects as a whole associated with LRRK2, is mainly due to the fact that pathogenic mutations increase the kinase activity of this enzyme, which has prompted an international race to develop inhibitors. Right now, specific, powerful inhibitors of the kinase activity of LRRK2 do in fact exist. Yet many of them cause undesirable side effects or produce very unclear clinical results.

This research conducted by Iban Ubarretxena, the Ikerbasque researcher and director of the Biofisika Institute (mixed centre of the CSIC-Spanish National Research Council and the UPV/EHU-University of the Basque Country) at the UPV/EHU’s Science Park (Leioa-Erandio Area), together with an international research team, has revealed that AdoCbl, one of the active forms of vitamin B12, acts as an inhibitor of the kinase activity of LRRK2 in cultured cells and brain tissue. It also significantly prevents the neurotoxicity of the LRRK2 variants associated with Parkinson’s in cultured cells of primary rodents, as well as in various genetically modified models used to study this disease. The results of the research have been published in the prestigious journal Cell Research.

So according to the study, vitamin B12 has turned out to be a new class of modulator of the kinase activity of LRRK2, which, as Iban Ubarretxena pointed out, “constitutes a huge step forward because it is a neuroprotective vitamin in animal models and has a mechanism unlike that of currently existing inhibitors. So it could be used as a basis to develop new therapies to combat hereditary Parkinson’s associated with pathogenic variants of the LRRK2 enzyme”.

 
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The research has presented strong evidence that Parkinson’s disease
begins in the gastrointestinal tract, and spreads via the vagus nerve
to the brain. Many patients have also suffered from gastrointestinal
symptoms before the Parkinson’s diagnosis is made.


Parkinson’s may begin in the gut and spread to the brain via the vagus nerve*

NEUROSCIENCE NEWS

A major epidemiological registry-based study from Aarhus University and Aarhus University Hospital indicates that Parkinson’s disease begins in the gastrointestinal tract; the study is the largest in the field so far.

The chronic neurodegenerative Parkinson’s disease affects an increasing number of people. However, scientists still do not know why some people develop Parkinson’s. Now researchers from Aarhus University and Aarhus University Hospital have taken an important step towards a better understanding of the disease.

New research indicates that Parkinson’s disease may begin in the gastrointestinal tract and spread through the vagus nerve to the brain.

“We have conducted a registry study of almost 15,000 patients who have had the vagus nerve in their stomach severed. Between approximately 1970-1995 this procedure was a very common method of ulcer treatment. If it really is correct that Parkinson’s starts in the gut and spreads through the vagus nerve, then these vagotomy patients should naturally be protected against developing Parkinson’s disease,” explains postdoc at Aarhus University Elisabeth Svensson on the hypothesis behind the study.

A hypothesis that turned out to be correct

“Our study shows that patients who have had the the entire vagus nerve severed were protected against Parkinson’s disease. Their risk was halved after 20 years. However, patients who had only had a small part of the vagus nerve severed where not protected. This also fits the hypothesis that the disease process is strongly dependent on a fully or partially intact vagus nerve to be able to reach and affect the brain,” she says.

The research project has just been published in the internationally recognised journal Annals of Neurology.

The first clinical examination

The research has presented strong evidence that Parkinson’s disease begins in the gastrointestinal tract and spreads via the vagus nerve to the brain. Many patients have also suffered from gastrointestinal symptoms before the Parkinson’s diagnosis is made.

“Patients with Parkinson’s are often constipated many years before they receive the diagnosis, which may be an early marker of the link between neurologic and gastroenterologic pathology related to the vagus nerve ,” says Elisabeth Svensson.

Previous hypotheses about the relationship between Parkinson’s and the vagus nerve have led to animal studies and cell studies in the field. However, the current study is the first and largest epidemiological study in humans.

The research project is an important piece of the puzzle in terms of the causes of the disease. In the future the researchers expect to be able to use the new knowledge to identify risk factors for Parkinson’s disease and thus prevent the disease.

“Now that we have found an association between the vagus nerve and the development of Parkinson’s disease, it is important to carry out research into the factors that may trigger this neurological degeneration, so that we can prevent the development of the disease. To be able to do this will naturally be a major breakthrough,” says Elisabeth Svensson.

 
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Iboagine and Parkinson's

by Hamilton Morris

One of the most interesting things that I have researched regarding ibogaine is its effect on a protein called GDNF – that’s Glial Cell Derived Neurotrophic Factor. And this is a protein that is very useful in the treatment of Parkinson’s disease. There’s been some limited clinical work where they showed that it can cause a regrowth of dopaminergic neurons, which is the mechanism of Parkinson’s. Damage to the brain is loss of dopaminergic neurons. So it’s directly reversing the toxic effect of Parkinson’s. And they found that ibogaine causes a release of the same therapeutic protein. So that’s pretty damn useful. And that’s just the tip of the iceberg with it. It also seems to synergize with dopaminergic drugs. So it’s possible that it increases patient sensitivity to the L-dopa treatment as well.

And on top of that, it seems to have an antidepressant effect, and depression is one of the major symptoms of Parkinson’s disease. So I think it could really be helping people with Parkinson’s. And there’s a sort of underground community of people with Parkinson’s that use ibogaine. And I occasionally receive emails from these people. Often they use it at 20 mg a day, and they seem to really believe in it as a treatment. On one hand, I understand that it’s irresponsible to talk about these things without a lot of serious medical support, but the flipside is that it needs to be studied. People need to be aware of it. There is no treatment available that’s actually addressing the root cause of the neurodegeneration. And if patients are being deprived that treatment, that’s a tragic thing.​
 
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Ibogaine and Parkinson’s

European Ibogaine Forum | 10 Sep 2017

GDNF (glial cell line-derived neurotrophic factor) is a protein discovered in 1991 with an extraordinarily positive effect on nerve cell tissue. GDNF stimulates nerve cell growth, especially dopamine neurons. In addition to the ability to regenerate nerve cells in the brain, GDNF also appears to possess neuroprotective properties.


In an animal experiment in which rats with Parkinson’s disease had GDNF injected directly into the brain, a significant improvement in the symptoms was observed. After one year, there were still no undesirable side effects of GDNF administration. Initial studies have shown that GDNF significantly improves the overall condition of Parkinsonian patients. The resulting data suggests that new nerve cells had formed.

Ibogaine and its metabolite noribogaine lead to a substantial increase in GDNF levels in the brain. This indicates that ibogaine could provide a very effective treatment for neurodegenerative diseases, such as Parkinsons.

Until now, it was not possible to introduce GDNF directly into the desired regions of the brain. But Ibogaine stimulates the glial cells and neurons to produce GDNF itself, increasing GDNF levels throughout the brain.

 Phytostan, a pharmaceutical company focused on developing ibogaine, has developed an ibogaine-based medicine called CK-BR 12. This consists of Ibogaine HCL and a cocktail composed of 12 vitamins.

Patient D is a 69-year-old Parkinson’s disease patient and until now the only human treated with Ibogaine for his condition. Patient D reported numerous positive changes regarding his illness: he could swallow again, speech and facial expressions improved, the control of the hands increased and he could write again legibly. Also, his general motor skills increased.

He could dress again, eat independently and climb stairs – all activities which were not possible prior to his treatment. The Parkinson’s symptomatology also improved after the treatment was completed. Patient D. was examined by various physicians as well as pharmacologist Dr. Susanne Cappendijk from Semper Clarus Consulting, who presented the promising results at the New York Academy of Sciences.

The standard symptomatic treatment, is predominantly carried out with drugs with strong side effects. The quality of life of the patients is often characterised by significant suffering in the terminal phase. In contrast, treatment with ibogaine, in particular through the approach of microdosing, allows an increase in the GDNF levels in the brain, without the side effects of conventionally used medications.

It was reported that 4mg Ibogaine HCL can increase GDNF levels in the brain by a factor of 12. The neuroplasticity increased by the growth of new neurons promotes the restoration and the construction of nerve tracts. Also, the challenge of introducing GDNF by injection into the brain is obviated. These results could help to redefine the position of Ibogaine in general research and – as ever-unknown healing properties of the plant are discovered – open up new research areas and thereby achieve a wider social and regulatory acceptance.

Novel variations of the ibogaine molecular structure have been developed that enhance the production of GDNF. The group of N-indolylethyl isoquinuclidines appears to be most promising. The synthesis of these molecules is far less complex than that of Ibogaine and there are several promising derivatives. Some of the analogues cause an even higher GDNF-release in vitro than Ibogaine does, but can have cytotoxic effects depending on the structure. The research in this field is still nascent, but it has enormous potential.

http://iboga.info/parkinsons-disease/
 
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New research shows that Parkinson’s originates in the gut

Neuroscience News | June 26, 2019

In experiments in mice, Johns Hopkins Medicine researchers say they have found additional evidence that Parkinson’s disease originates among cells in the gut and travels up the body’s neurons to the brain. The study, described in the June issue of the journal Neuron, offers a new, more accurate model in which to test treatments that could prevent or halt Parkinson’s disease progression.

“These findings provide further proof of the gut’s role in Parkinson’s disease, and give us a model to study the disease’s progression from the start,” says Ted Dawson, M.D., Ph.D., director of the Johns Hopkins Institute for Cell Engineering and professor of neurology at the Johns Hopkins University School of Medicine.

Parkinson’s disease is characterized by the buildup of a misfolded protein, called alpha-synuclein, in the cells of the brain. As more of these proteins begin to clump together, they cause nerve tissues to die off, leaving behind large swaths of dead brain matter known as Lewy bodies. As brain cells die, they impair a person’s ability to move, think or regulate emotions.

"The new study builds off observations made in 2003 by German neuroanatomist Heiko Braak that showed people with Parkinson’s disease also had accumulations of the misfolded alpha-synuclein protein in the parts of the central nervous system that control the gut. The appearance of these neuron-damaging proteins is consistent with some early symptoms of Parkinson’s disease, which include constipation," says Hanseok Ko, Ph.D., associate professor of neurology at the Johns Hopkins University School of Medicine. Braak hypothesized that "Parkinson’s disease advanced up the nerves connecting the gut and the brain like going up a ladder."

A growing body of evidence has implicated the gut-brain connection in initiating Parkinson’s disease. The researchers were most curious whether the misfolded alpha-synuclein protein could travel along the nerve bundle known as the vagus nerve, which runs like an electrical cable from the stomach and small intestine into the base of the brain.

To test this, the researchers injected 25 micrograms of synthetic misfolded alpha-synuclein created in the lab into the guts of dozens of healthy mice. The researchers sampled and analyzed the mouse brain tissue at one, three, seven and 10 months after injection. Over the course of the 10-month experiment, the researchers saw evidence that the alpha-synuclein began building where the vagus nerve connected to the gut and continued to spread through all parts of the brain.

"The researchers then conducted a similar experiment, but this time surgically cut the vagus nerve in one group of mice and injected their guts with the misfolded alpha-synuclein. Upon examination at seven months, the researchers found that mice with severed vagus nerves showed none of the signs of cell death found in mice with intact vagus nerves. The severed nerve appeared to halt the misfolded protein’s advances," says Dawson.

The researchers then investigated whether these physical differences in Parkinson’s disease progression resulted in behavioral changes. To do this, they evaluated the behavior of three groups: mice injected with misfolded alpha-synuclein, mice injected with misfolded alpha-synuclein with cut vagus nerves, and control mice with no injection and intact vagus nerves. The researchers looked at tasks they commonly used to distinguish signs of mouse Parkinson’s disease, including nest building and exploring new environments.

The researchers first observed the mice build nests in their enclosure as a test for fine motor dexterity, which is commonly affected by Parkinson’s disease in humans. Healthy mice often make large, dense mounds in which to burrow. Smaller, messier nests are often signs of problems with motor control.

Seven months after injection, the researchers provided the mice with nesting materials and observed their nest building behavior for 16 hours, scoring their capabilities on a scale of 0-6. They found that mice that received the misfolded alpha-synuclein injection scored consistently lower on nest building.

"While the control and severed vagus nerve groups consistently scored 3 or 4 on the nest building scale, mice that received the misfolded alpha-synuclein scored lower than 1. Also, while most mice used the entire 2.5 grams of material provided, the group of mice that received the alpha-synuclein injection used less than half a gram of the nesting material. In ways similar to Parkinson’s disease symptoms in humans, the mice’s fine motor control deteriorated as the disease progressed," says Ko.

In another experiment analyzing the mice for symptoms similar to Parkinson’s disease in humans, the researchers measured anxiety levels of the mice by monitoring how they responded to new environments.

For this test, the researchers placed the mice in a large open box where a camera could track their exploration. Healthy mice are curious and will spend time investigating every part of a new environment. However, mice affected by cognitive decline are more anxious, causing them to be more likely to stay toward the sheltered edges of a box.

The research team found that control mice and mice that had their vagus nerves cut to protect against Parkinson’s disease spent between 20 and 30 minutes exploring the center of the box. On the other hand, mice that received the misfolded alpha-synuclein injection but had intact vagus nerves spent less than five minutes exploring the center of the box and moved mostly around the borders, indicating higher anxiety levels, which the researchers report are consistent with symptoms of Parkinson’s disease.



In experiments in mice, Johns Hopkins Medicine researchers say they have found additional evidence that Parkinson’s disease originates among cells in the gut and travels up the body’s neurons to the brain. The study offers a new, more accurate model in which to test treatments that could prevent or halt Parkinson’s disease progression.

Overall, the results of this study show that misfolded alpha-synuclein can be transmitted from the gut to the brain in mice along the vagus nerve, and blocking the transmission route could be key to preventing the physical and cognitive manifestations of Parkinson’s disease.

“This is an exciting discovery for the field and presents a target for early intervention in the disease,” says Dawson.

Next, the researchers say, they plan to explore what parts of the vagus nerve allow the misfolded protein to climb to the brain, and to investigate potential mechanisms to stop it.


 
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Cambridge
Ibogaine & Parkinson’s Disease

GLOBAL IBOGAINE THERAPY ALLIANCE

Parkinson’s Disease is classified as a neurodegenerative disorder, one characterized by the progressive atrophy of the central and peripheral nervous system. However, some evidence suggests that the neurodegeneration in Parkinson’s subjects may be caused by the body’s own immune system losing the ability to determine between healthy and unhealthy cells, as is the case with autoimmune diseases such as Fibromyalgia, Multiple Sclerosis and others, in which much of the body’s organs and cell tissue deteriorate because of misdirected attack by the immune system.

Although the theory is still untested, there is anecdotal evidence and a theoretical framework that suggests ibogaine may have therapeutic benefits in the treatment of Parkinson, and possibly other disorders that cause the degeneration of brain and cell tissues.

The theoretical case is based on the fact that both ibogaine and its metabolite noribogaine have been shown to lead to an increase in levels of glial cell line-derived neurotrophic factor (GDNF) in the brain. It has also been shown to have neuroprotective qualities promoting the survival of both dopaminergic and motor neurons.

In other research, neutrophic factors, specifically GDNF, have been shown to cause sprouting of dopaminergic fibers, with a resulting improvement of clinical symptoms of Parkinson’s in experimental animal models and humans. However, there is little research available using neutrophic factors in the treatment of other neurodegenerative disorders, particularly because administration is usually limited by toxicity or poor bioavailability. Various other methods of administration such as direct brain infusion of GDNF and gene therapy that promotes the expression of neurotrophic factors have been explored.

The direct brain infusion of GDNF into the brains of five rats induced with Parkinson’s disease showed a 39% improvement in off-medication motor sub-score of the Unite Parkinson’s Disease Rating Scale (UPDRS), and a 61% improvement in the activities of daily living sub score. After one year, no side effects from the treatment were observed.

In addition to Parkinson’s, one study using gene therapy that promotes the expression of neurotrophic factors, showed a 50% increase in life span, reduced loss of motor axons and improved neuromuscular function in animal models representing Motor Neuron Diseases. The study suggested further research into neurotrophic factor as a treatment for MND.

Parkinson’s and similar diseases have no known cure, and these conditions often require management with drugs that have considerable side effects, causing a very poor quality of life for terminal stage sufferers of these diseases.

Ibogaine therapy, especially low-dose regimens, may facilitate the expression of GDNF without the side effects of other medications or the difficulty of other avenues of administering neurotrophic factor. Anecdotal reports suggest that at least several people with Parkinson’s who have been treated with ibogaine have seen an extended remission of symptoms.

Although there is little clinical research into this particular application, one of the first studies to assess ibogaine efficacy, specifically in the treatment of Parkinson's disease in animal models, is currently underway at Columbia University.

https://www.ibogainealliance.org/ibo...py/parkinsons/
 
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Findings suggest that vitamin D supplementation may help to treat non-motor symptoms
associated with Parkinson’s.

Low vitamin D levels linked to symptoms in patients with Parkinson’s disease

Neuroscience News | Aug 7 2019

Vitamin D deficiency is widespread in patients with Parkinson’s disease (PD). Our aim was to determine whether serum vitamin D levels correlated with bone mineral density (BMD) and non‐motor symptoms in patients with PD.

In an Acta Neurologica Scandinavia study of 182 patients with Parkinson’s disease and 185 healthy controls, patients with Parkinson’s disease had significantly lower levels of vitamin D in their blood. Also, patients with lower vitamin D levels were more likely to fall, and to experience sleep problems, depression, and anxiety.

The findings suggest that vitamin D supplementation may help to treat non-motor symptoms associated with Parkinson’s disease.

“As various non-motor symptoms place a burden on individuals with Parkinson’s disease and their caregivers, vitamin D might be a potential add-on therapy for improving these neglected symptoms,” said senior author Chun Feng Liu, MD, PhD, of the Second Affiliated Hospital of Soochow University, in China.

Patients with PD had significantly lower serum levels relative to healthy controls. After adjusting for age, sex, and body mass index, vitamin D levels significantly correlated with falls, insomnia, and scores for the PSQI, depression, and anxiety.

Conclusions

In patients with PD, vitamin D levels significantly correlated with falls and some non‐motor symptoms. However, no associations were found between BMD and the serum levels in patients with PD. Thus, vitamin D supplementation is a potential therapeutic for non‐motor PD symptoms.

 
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Clinical trial to repurpose ketamine for Parkinson's*

by Maria Cohut | Medical News Today | 20 July 2018

The drug used to manage some of the most salient symptoms of Parkinson's disease is known to expose patients to more motor issues, as part of its side effects. Researchers suggest that ketamine could be used to neutralize those side effects.

Parkinson's disease, a motor system disorder, is characterized by tremor, limb stiffness, impaired balance, and slowness of movement, as well as impaired movement coordination.

There is currently no known cure for this disorder, so treatments focus largely on managing the symptoms.

This helps people maintain autonomy and quality of life, as much as possible.

One of the main drugs used to treat Parkinson's disease is levodopa, which can help with limb stiffness and slowness of movement. But there is a caveat: patients for whom levodopa does work begin to experience potentially debilitating side effects after a few years on the drug.

"The problem is levodopa works great for a few years — we call that the 'honeymoon' period — but then you start getting these side effects," notes Dr. Scott Sherman, a neurologist at the University of Arizona College of Medicine in Tucson.

So what happens to many patients who take levodopa? They develop dyskinesia, or involuntary and uncontrollable movements that can affect the limbs, the head, or even the entire body, to various degrees of severity.

Once an individual develops levodopa-related dyskinesia, it does not go away unless treatment with this drug is discontinued altogether — though this may mean that their symptoms will no longer be managed.

But is there anything that could counteract levodopa's side effects? Dr. Sherman and colleague Torsten Falk believe that the answer may lie with ketamine.

Ketamine's effect on dyskinesia

Dr. Sherman and Falk found the first clues about ketamine's potential in offsetting dyskinesia when they tested it as a pain-relieving drug for patients with Parkinson's.

Their trial led them to observe an unintended yet welcome effect: dyskinesia was ameliorated, or even disappeared completely for a few weeks in the case of individuals on levodopa who were also administered ketamine.

When the researchers tried to duplicate these findings in a rat model, they found that the dyskinesia-offsetting effects of ketamine held strong.

This has led them to plan a controlled clinical trial in the hopes of discovering how — or whether — ketamine might best be used in conjunction with levodopa to treat patients with Parkinson's disease.

Ketamine's best-known side effect is dissociation (also known as disassociation), in which a person feels as though they are perceiving the world from some place outside of their own bodies. This uncanny effect is also why ketamine has notoriously been misused as a "party drug."

"Disassociation is a sort of 'out-of-body' experience. When people describe it, they have told me that they feel like they are in fish bowl," explains Dr. Sherman.

Another common risk of taking ketamine is raised blood pressure. However, the scientists are strategizing to keep these possible effects in check by carefully calculating dosage.

According to Dr. Sherman, "We are going to monitor blood pressure closely to make sure it doesn't get high. And," he continues, "we know at what dosage ketamine causes this disassociation; we expect that the dosage needed in Parkinson's disease will stay well below that level."

"Ketamine has been long overlooked. Now it could prove very useful for Parkinson's patients,"
said Dr. Sherman.

*From the article here :
 
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Rutgers University

Discovery could help slow down or even stop the progression of Parkinson's*

by Jillian Prior | Rutgers University | 28 Jan 2020

A collaboration between scientists at Rutgers University and Scripps Research has led to the discovery of a small molecule that may slow down or stop the progression of Parkinson's disease.

Parkinson's, which affects 1 million people in the United States and over 10 million worldwide according to the Parkinson's Foundation, is a neurodegenerative disorder with no cure. Symptoms develop slowly over time and can be debilitating to patients, who most recognizably develop tremor, slow movements and a shuffling gait.

A key feature of Parkinson's disease is a protein named α-synuclein, which accumulates in an abnormal form in brain cells causing them to degenerate and die. However, it has been difficult to target α-synuclein because it does not have a fixed structure and keeps changing its shape, making it very difficult for drugs to target. Because higher levels of the protein in the brain speed the degeneration of brain cells, scientists have been looking for ways to decrease the protein production as a form of treatment.

In 2014, Parkinson's disease expert and scientist M. Maral Mouradian, William Dow Lovett Professor of Neurology and director of the Rutgers Robert Wood Johnson Medical School Institute for Neurological Therapeutics, contacted Matthew D. Disney, chemistry professor at Scripps Research in Florida, to explore a novel idea for treating Parkinson's disease using a new technology developed by Disney.

Disney's method matches RNA structure with small molecules or drug-like compounds. The two collaborators believed this innovative technology could be used to find a drug that targets the messenger RNA that codes for α-synuclein, which causes the disease, in order to reduce production of the protein in the brains of Parkinson's patients. Since the protein itself can't be treated with drugs, RNA could be a more robust and reliable target.

They were right. The NIH-funded study, which was published in the Proceedings of the National Academy of Sciences on January 3, showed that by targeting messenger RNA, the team found a compound that prevents the harmful Parkinson's protein from being made. This new compound, named Synucleozid, reduces specifically α-synuclein levels and protects cells against the toxicity of the misfolded form of the protein, suggesting that it has the potential of preventing disease progression.

"We found the molecule to be very selective at both the RNA level and the protein level," Disney says.

"Currently, there is no cure for Parkinson's disease, and it is truly a devastating disease. For the first time, we discovered a drug-like compound that has the potential to slow down the disease before it advances through an entirely new approach," said Mouradian. “Such a treatment would be most effective for people who are in the early stages of the disease with minimal symptoms,” she said.

"Several other experimental drugs currently being tested for Parkinson's disease are antibodies that target a very late stage of α-synuclein protein aggregates. We want to prevent these protein clumps from forming in the first place before they do damage and lead to advancing disease.," she said. "This new compound has the potential to do that and could change the course of life for people with this devastating disease."

Mouradian says this discovery is 'highly promising' and is eager for the next steps in optimizing and testing the compound. Additionally, this can benefit another devasting disease that also has α-synuclein clumps, known as Dementia with Lewy Bodies. Further, this new concept of targeting RNA to reduce protein production developed in Disney's lab at Scripps Research may be applied to other challenging diseases because of their similar undruggable proteins including Alzheimer's disease.

"The reach of our study could go beyond people with Parkinson's disease to many other neurodegenerative diseases. It is a classic example of how interdisciplinary research leads to significant change," she said.

 
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Support grows for medical device that improves communication for those with Parkinson's*

by Purdue University | Medical Xpress | Nov 20 2019

A growing number of people with Parkinson's disease are finding the ability to communicate with a wearable device developed by a Purdue University speech-language researcher and entrepreneur.

SpeechVive uses a reflex to improve communication. The device plays noise in a user's ear when they are talking, which elicits the reflex, resulting in speech that is automatically louder, clearer and lower.

"Since the wearable device elicits a reflex, the patient does not need to remember to use therapy techniques to communicate in everyday life," said Jessica Huber, a professor in Purdue's Department of Speech, Language, and Hearing Sciences, who developed SpeechVive. "When people with Parkinson's disease cannot be heard or understood, they withdraw from communication exchanges, leading to social isolation. This device makes it possible for patients to continue to communicate with their loved ones well into their disease."

SpeechVive Inc. commercialized the Purdue device to help the more than a million people in the United States who are diagnosed with Parkinson's, one of the most common degenerative neurological diseases. Veterans can receive the device through their local VA hospital as a part of their health care benefits.

"We are working to develop additional routes for individuals to obtain the device," said Huber. "I enjoy developing and testing devices and therapies that can improve the quality of life for people with Parkinson's disease."

*From the article here:

 
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Is anyone else with Parkinson's trying ibogaine?

I started a low dose regime of ibogaine a few days ago and the results are remarkable in just a few days. My neurologist is aware that I am doing this and was supportive. I was wondering if anyone else has tried it. I am taking two 20 mg doses per day. I am currently using ibogaine HCL but plan on switching to the plant extract when that runs out.

Tremors have steadily been diminishing. Steady decrease in shoulder and neck tension. Arms now swing naturally. Big improvement in speech. A "spring" in my step. Regaining sense of smell. Toe curling almost gone. Feeling of being in a fog is gone. Daily improvement in energy. These improvements have been getting better every day so far.

I am currently taking approximately 20 mg of ibogaine HCL twice a day together with a B vitamin complex that approximates the B vitamins in this patent for an ibogaine medication for treating PD:

The dose for treating addictions is known as a "flood" dose and is in the range of hundreds of milligrams not tens of milligrams. The abuse dosages are also in the hundreds of mg range. Micro-dosing is far different. I can tell you that I experience no inebriation at the dosage I am using.

The literature on ibogaine suggests that it "resets" the adrenaline, serotonin, and dopamine systems in the brain. There is a disagreement about whether the dopamine producing cells in the substantia nigra die or go dormant. Most seem to think they die, but a minority think they simply have gone dormant. I am hoping they are dormant and ibogaine provides a wake-up call.

If it is dormancy and not death, a long term treatment is not required. The course only needs to be pursued until reset. BTW this is the method used by the ibogaine addiction residential treatment centers. They only use a "flood" dose to reset and that is it. Sometimes multiple "flood" doses but not the micro-dose I use for PD.

Scoring is difficult. All I know is that I no longer experience toe curling, my tremor is greatly reduced, the stiffness in my neck and shoulders is greatly reduced, my feet don't feel so leaden when I walk, and my sense of smell has been returning. Before ibogaine I had incidents of toe curling and foot cramps almost every day. Some days I could barely walk. I have only had one mild instance of foot cramping since I began this experiment.

I have noticed no psychoactive effects from ibogaine. I am taking 20 mg twice a day together with an over the counter B vitamin cocktail that approximates the B vitamin complex that is in the ibogaine patent for PD.

My PD symptoms first showed up in 2008. I obtained a small quantity of ibogaine hcl and last November started taking 20mg daily. In December I quit the ibogaine for a few weeks until I got over a nasty virus. I had read a drug interaction warning about ibogaine and dextromethorphan, ingredient in otc cough syrup. Then I resumed taking it until March when I ran out.

The positive results were mostly a clearing of the 'brain fog' and a much higher energy level. My gross motor symptoms had always been in good control (most people couldn't tell I have PD), but I experienced a bit of improvement in what tremors and dyskinesia I had. I'm hoping to get some more ibogaine and continue my treatment.

There is a debate over whether the dopamine neurons in the substantia nigra have died or are dormant in PD. The effect of ibogaine is believed to be, at least in part, the revival of dormant cells and/or the neurogenesis of new cells. It is believed to do this by increasing the amount of GDNF in the brain. So this is why I want to eliminate sinemet, to remove the potential interference in the feedback mechanism that sinemet must interfere with. Also, sinemet metabolites are known to be toxic.

I'm giving this a 180 day trial, and I'm only 3 weeks into it, but am quite happy with the results so far.

-danfitz

https://healthunlocked.com/parkinsonsmovement/posts/137612000/anyone-else-trying-ibogaine
 
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How a protein wreaks havoc in those with Parkinson's*

by Ciara O'shea | Trinity College Dublin | 13 Feb 2020

What causes neurons to die in people with Parkinson's?

Parkinson's disease is a long-term (chronic) neurological condition that affects around 12,000 people in Ireland and between 7 and 10 million people worldwide.

The disease affects the way the brain co-ordinates body movements like walking and talking, but cognitive abilities are also affected.

There is currently no cure for the disease, but researchers at Trinity have recently published findings of a study which may lead to better treatments for this debilitating illness. The paper has been published in the international Cell Press journal, Structure.

Neurons in the part of the brain called 'substantia nigra' (dark matter) produce and release a hormone called dopamine. This hormone acts as a messenger between these cells in the substantia nigra and other parts of the brain which control body movements.

"If these specialized neurons become damaged or die, the amount of dopamine in the brain is reduced. This means that the parts of the brain that control movement cease to function normally. The only treatment for Parkinson's disease in the last 20 years has been dopamine replacement therapy. This involves providing a substitute to try to increase the levels of the hormone in the brain. However, the treatment is not completely effective and can wear off over time, and it also has side effects," said Amir Khan, Associate professor, School of Biochemistry and Immunology at Trinity. "The main reason why we lack new treatments is that we don't understand the fundamental mechanism of how neurons become sick and die. No one knows why these particular neurons in the substantia nigra are affected.”

"In the last few years, the field has completely changed. We have new insight into a gene called LRRK2, which is the most common cause of inherited Parkinson's disease. Although only 10% of Parkinson's cases are inherited, the enzyme that is produced by the LRRK2 gene seems to be overactive in both inherited and 'sporadic' cases."

"In other words, afflicted individuals may not have an LRRK2 mutation, but the enzyme 'runs amok' in their neurons anyway. Inhibitors of this enzyme are now in late clinical trials for treatment of Parkinson's disease."


The team at Trinity has studied the effects that LRRK2 has on other proteins in neuronal cells. To understand how LRRK2 affects the brain and leads to Parkinson's disease, the team has simulated the activity of the enzyme in the laboratory.

"The research allowed us to visualize the 3-D structure of a protein complex that is formed when LRRK2 is overactive. From these structural studies of proteins, we can understand how LRRK2 is able to impose its profound effects on neurons. We are the first group to report the effects of LRRK2 in 3-D detail using a method called X-ray crystallography," Professor Khan continued.

"An overactive LRRK2 runs loose in neurons and wreaks havoc on motor and cognitive abilities. In a way, we are chasing the footprints that LRRK2 leaves in the brain to understand what it does, and find ways to stop it."

"We are hopeful that these studies may eventually lead to new treatments for Parkinson's disease, for which there is currently no cure,"
he said.

*From the article here :
 
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University of Technology Sydney

Scientists discover medicinal cannabis substitute for treating Parkinson’s

University of Technology Sydney | Neuroscience News | Dec 20 2019

The drug – HU-308 – lessens the devastating involuntary movements called dyskinesias, a side effect from years of treatment for Parkinson’s.

The research, published today in Neurobiology of Disease, has been conducted by the Centre for Neuroscience and Regenerative Medicine (CNRM) at the University of Technology Sydney (UTS) and the Applied Medical Research Institute of St Vincent’s Hospital Sydney.

The study shows that in mice HU-308 is as effective as Amantadine, the only available treatment for dyskinesias. Furthermore, the combination of HU-308 with Amantadine is more effective than either drug used alone.

Professor Bryce Vissel, director of the CNRM and senior author of the study, said the findings present the possibility of new options for Parkinson’s patients.

“Our study suggests that a derivative of HU-308, either alone or in combination with Amantadine, may be a more effective treatment for dyskinesias and a much better option than using an unproven potentially harmful substance like cannabis,” Professor Vissel said.

“Currently there is limited evidence about the effectiveness of medicinal cannabis. One problem is that no cannabis preparation is the same and cannabis has numerous effects, some of which may not be beneficial in Parkinson’s disease.”

Cannabis works on several receptors in the brain – CB1 and CB2. The psychoactive effect is caused mostly because of receptor CB1.

Professor Vissel said the HU-308 drug explored by his team works only on receptor CB2, allowing medicinal benefits to be administered without causing psychoactive effects like drowsiness or highness.

Lead author Dr Peggy Rentsch said it is unclear whether medicinal cannabis itself can help Parkinson’s patients.

“Medicinal cannabis contains different compounds, some of which make you high and which can impact a person’s normal day-to-day activities,” Dr Rentsch said.

“Our research suggests HU-308 is an important prototype drug which we believe won’t interfere with patients’ day-to-day activities. They should maintain normal levels of mental sharpness on a treatment like this.”

Professor Vissel and his team are investigating ways to block inflammation of the brain to maintain and restore memory and slow the progression for both Parkinson’s disease and Alzheimer’s disease.

“HU-308 works by reducing inflammation in the brain, affecting the neurons and immune cells.”

“In neurological disorders, the immune cells in the brain can lose supportive function with adverse stimuli – including but not limited to trauma or obesity – and become ‘activated.’ Scientists at the CNRM believe that, after this activation, the immune cells backfire, kill the brain’s neurons, destroy them – and become dysfunctional."

“By reducing inflammation in the brain – such as with HU-308 – these immune cells can support normal neural function again, rather than inhibiting it.”


Study collaborator Dr Sandy Stayte said: “The fact that Amantadine has its own set of side effects, may not work in the long term, and is still the only drug available on the market that is approved for dyskinesias makes our study really exciting."

“First, our study shows HU-308 is equally affective so a drug like HU-308 will be useful for those people who can’t take Amantadine. Second, for those who can tolerate amantadine, taking the combination may have even greater benefits than taking either drug alone. That means we may end up with a much more powerful treatment than currently available by ultimately prescribing both.”


 
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Thanks to exciting novel therapies, there's hope on the horizon for individuals and families affected by Parkinson's.

Novel treatment for Parkinson's using patient's own cells

by McLean Hospital | Medical Xpress | 13 May 2020

Reprogramming a patient's own skin cells to replace cells in the brain that are progressively lost during Parkinson's disease (PD) has been shown to be technically feasible, reports a team of investigators from McLean Hospital and Massachusetts General Hospital (MGH) in the most recent issue of the New England Journal of Medicine.

PD is the second most common degenerative disease of the brain, and millions of people world-wide experience its symptoms, which include tremor, stiffness, and difficulty with speech and walking. The progressive loss of brain cells called dopaminergic neurons plays a major role in the disease's development. As described in the current report, the use of a patient's own reprogrammed cells is an advance that overcomes barriers associated with the use of cells from another individual.

"Because the cells come from the patient, they are readily available and can be reprogrammed in such a way that they are not rejected on implantation. This represents a milestone in 'personalized medicine' for Parkinson's," says senior author Kwang-Soo Kim, Ph.D., director of the Molecular Neurobiology Laboratory at McLean Hospital, the largest clinical neuroscience and psychiatric affiliate of Harvard Medical School.

The McLean-MGH team reprogrammed a 69-year-old patient's skin cells to embryo-like pluripotent stem cells (called induced pluripotent stem cells) and then differentiated them to take on the characteristics of dopaminergic neurons, which are lost in Parkinson's. After extensive testing of the cells, Kim applied for and gained approval under the FDA's single-patient, expanded-access protocol to implant the cells into the patient's brain.

Bob Carter, MD, Ph.D., chief of Neurosurgery at MGH and co-senior author, says: "This strategy highlights the emerging power of using one's own cells to try and reverse a condition—Parkinson's disease—that has been very challenging to treat. I am very pleased by the extensive collaboration across multiple institutions, scientists, physicians, and surgeons that came together to make this a possibility."

In a series of two separate surgeries in 2017 and 2018 at Weill Cornell Medical Center and MGH, the patient underwent transplantation of the replacement dopamine neurons. Lead author Jeffrey Schweitzer, MD, Ph.D., a Parkinson's specialized neurosurgeon and director of the Neurosurgical Neurodegenerative Cell Therapy program at MGH, designed a novel minimally invasive neurosurgical implantation procedure to deliver the cells, working in collaboration with Carter at MGH and Michael G. Kaplitt, MD, Ph.D., a neurosurgeon at Weill Cornell.

Two years later, imaging tests indicate that the transplanted cells are alive and functioning correctly as dopaminergic neurons in the brain. Because the implanted cells originated from the patient, they did not trigger an immune response and were not rejected without the use of an immunosuppressant drug. Kim also noted, "We have shown for the first time in this study that these reprogrammed cells are still recognized as self by the patient's immune system and won't be rejected." These results indicate that this personalized cell-replacement strategy was a technical success, with the cells surviving and functioning in the intended manner. The patient has not developed any side effects, and there are no signs that the cells have caused any unwanted growth or tumors.

As for how the patient feels, in the time that has passed since surgery, the patient has enjoyed improvements in his day-to-day activities and reports an improvement in his quality of life. Routine activities, such as tying his shoes, walking with an improved stride, and speaking with a clearer voice, have become possible again. Some activities—such as swimming, skiing, and biking, which he had given up years ago—are now back on his agenda. While it is too early to know whether this treatment approach is viable based on a single patient, the authors have the goal of continuing to test the treatment in formal clinical trials.

"Current drugs and surgical treatments for Parkinson's disease are intended to address symptoms that result from the loss of dopaminergic neurons, but our strategy attempts to go further by directly replacing those neurons," says Kim.

"As a neurologist, my goal is to make state-of-the-art treatments available to patients with Parkinson's," says Todd Herrington, MD, Ph.D., lead study neurologist at MGH and Parkinson's expert. "If the benefits seen in this proof-of-principle case are confirmed in formal clinical studies, this line of research could deliver an entirely new therapeutic approach to offer patients with Parkinson's."

While there is optimism about the future of Parkinson's disease treatments because of their work, Schweitzer cautions against declaring victory against the disease.

"These results reflect the experience of one individual patient, and a formal clinical trial will be required to show whether Parkinson's patients, in general, could expect improvements like this," says Schweitzer. "With that said, the outcome is extremely encouraging for the future prospects of this technique."

 
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Microdosing ibogaine for Parkinson's

by Lakshmi Narayan and Eric Swenson | Awake.net

Patient D is a 76-year old individual who was diagnosed with Parkinson’s five years ago and has been able to manage and improve his symptoms by microdosing ibogaine. He remains anonymous because of the legal status of ibogaine. Ibogaine is an entheogenic plant medicine that has helped him to have a semblance of health and vitality even with such a crippling disease as Parkinson’s. We spoke with Patient D about his experiences.

LN: How old were you when you were diagnosed with Parkinson’s?

Patient D: I’m 76 now, I was 71 when I was diagnosed with Parkinson’s.

ES: And I understand that your doctor diagnosed you with “atypical” Parkinson’s. What was atypical about it, beyond the fact that you had no tremors?

Patient D: That’s all. In fact, most of the people with Parkinson’s don’t have tremors.

ES: Oh, I didn’t know that. I thought that was pretty standard.

Patient D: Yeah. I probably know more about Parkinson’s than most doctors. I’m an authority on the subject because I can put words to what I experienced and they can’t. They don’t know what I’m talking about with Parkinson’s.

ES: Right. People have told me that with Parkinson’s everything is diminished.

Patient D: That’s it. Everything.

ES: What is your ability to smell? That is another issue for many Parkinson’s sufferers.

Patient D: Smell and taste have been coming back very slowly. They disappeared completely. But now I can smell, I can taste. It was gone for a long time. I now sense more improvement rather than more problems happening with my Parkinson’s.

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I’m a member of the local Parkinson’s group. There are about 150 people that come once a month. And it’s quite an education. I can’t talk to anybody about what I’m doing, because I used to–and they all got very paranoid.

They’d say, “Well, how do you spell that?” And I spelled it for them.

I-B-O-G-A-I-N-E

When they look on the web, all they can find is, it’s about heroin addiction. It’s used for heroin. It just freaked them out. They didn’t want to have anything to do with it.

LN: I see. Well, that’s very enlightening, because it’s as though ibogaine, the medicine itself, has been stigmatized by association.

Patient D: That’s right. So I have not had one person that I’ve talked to at the local group that wants to do it. Not one. I did a lecture in Mexico four or five years ago, and there were a couple people at that conference who were doing it because of what had happened to me a year before, when I took it for the first time. And they’re still taking it, and they’re still just about the same as I am.

LN: So could you describe what happened when you took it for the first time?

Patient D: I started taking it in November of 2014. I heard about it from some people in New York, ex-heroin addicts, who believed that because Parkinson’s affects dopamine, they had found that ibogaine helps the creation of dopamine through providing GDNF. It’s a neuronal approach to it. GDNF helps the neurons grow and secrete dopamine, so they thought maybe it will increase the flow of dopamine in Parkinson’s people, from another place, a different place than the substantia nigra, which is that little teeny piece in the brain that creates it.

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Parkinson’s disease (PD) is a neurodegenerative disorder that affects predominantly dopamine-producing (“dopaminergic”) neurons in a specific area of the brain called substantia nigra. Parkinson’s symptoms generally develop slowly over years. The progression of symptoms is often a bit different from one person to another due to the diversity of the disease. The cause remains largely unknown. People with PD may experience: tremor, bradykinesia, limb rigidity, gait and balance problems.

LN: What made you decide to take Ibogaine when nobody else had taken it for Parkinson’s— what did you do, how did you find it, where did you go, what did it do for you afterwards?

Patient D: I’m it. I mean, I really am. I’m the guinea pig. And, it’s all sort of anecdotal evidence. There’s no scientific rigor applied here. So you can’t really use me as a scientific study. Although I can tell you from first-hand experience that this stuff, ibogaine, it’s incredible. And these people are silly for not wanting to do it, but they associate it with crime and drugs. And I don’t want to be associated with that, in their eyes, either. Because I’ve been down once. I don’t want to go down again.

So what happened to me was, I had some friends that were friends with these people in New York that had access to ibogaine, and one of them had used it to cure his heroin addiction. He’s now probably 75. He thought that this was going to be a business for him, making it available for Parkinson’s patients, and he gave me enough to use — he had it pre-packaged in very small microdose amounts. I started out taking four milligrams, twice a day, for a week, and then I did that for two weeks.

And even at four milligrams, which is a very small amount, after two weeks I had VAST improvements.

All my joints used to ratchet, they’d go click, click click click click, when I’d try to go through a movement. And now they’re smooth; I can stand up now, and walk down a straight path, and do a U-turn, and come right back without a problem. Parkinson’s people, it takes them three or four steps to make a U-turn. That was me before I started this, I was doing that. You freeze in place, where you can’t move. You have to struggle to get your body to want to follow your orders. So I felt really, when I discovered that I had it, that I had a death sentence imposed on me. Parkinson’s is a death sentence. And I don’t want to die. I’m not ready to die yet. I’ve got young kids, relatively young, now, I’m considering. So, I said sure I’ll take that stuff. I wasn’t afraid of psychedelics. I did and it worked a bit, and it keeps working. I’m very happy.

ES: So I’m interested in the dosage. It is what microdosers call “sub-perceptual,” correct? You do not have a psychedelic effect taking a microdose?

Patient D: You’re correct. I do not have a psychedelic effect. I started out at eight milligrams a day. And after a month I was taking twice and then three times that. “This is working. I should keep trying more!” Which is, I guess, the age-old “more is better” concept. I ended up taking 40 milligrams, twice a day. 80 milligrams. It’s not very much. Except my friend in Canada is doing 20 milligrams, twice a day. And he’s had the same effect. So I’m gonna try and take less. See what happens. And I’ve tried to take less before, and it didn’t work. I have to take this much to maintain where I’m at.

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LN: So the other people who took it, did they also feel better?

Patient D: Oh yeah. One guy is a carpenter, and he had to quit working because of his Parkinson’s. He’s 55 and now he’s working and building a house in Canada. His body is working again. He rides a bicycle. The key also, besides Ibogaine, the other key, is a lot of exercise. I can’t ride a bicycle because of my balance condition, but I have a bicycle machine that I strap myself into. And it pedals me. I can resist it, I can decrease pressure on it. But I ride on that and I ride an hour a day.

It’s really a shame that this isn’t available through a prescription through a medical provider, where I could talk more freely to people and let them look at me, let them measure me, let them test me. I’ve had blood tests every year since November of 2014. My annual physical, my blood, has not changed in the slightest amount. So somehow it’s working.

I had a heart echogram yesterday. I’m absolutely normal for somebody my age. A very small amount of thickening of one muscle, for hypertension. I’ve had high blood pressure for 30 years. The only thing I hate about sitting is you get a little bit of a belly. I normally was very thin and active most of my life. Aging is what it is. It’s just some other thing you face.

LN: So you started to take this ibogaine microdose and then you continued to ramp up, and now you’re on a maintenance dose. And that’s like going to be for the rest of your life, you think?

Patient D: If I can maintain my supply, and that’s not easy. It’s the hardest part of the whole game. That’s why I’m so paranoid. I don’t want the risk when having to cross the border. I have to leave this country. I don’t want my face to pop up.

LN: I see.

Patient D: And they can be as vicious as they want to be.

LN: I can see that you would want to be cautious.

Patient D: I was writing a script on marijuana smuggling. I was around people who were smugglers. I was worming my way into their trust. I never actually dealt anything with them. It was all something that was going to happen in the future. But the DEA was monitoring this whole thing. They didn’t know that I was not involved. But when I presented my defense at trial, they didn’t care. I mean, I was tried with two other guys that did do a deal. And I got a 15-year sentence of which I served five. So I don’t want to go back.

LN: It’s a cautionary tale.

Patient D: It was an experience. I don’t regret that I was there. But I don’t want to go back again. It would be too hard at my age. They don’t have any accommodation for disabilities.

LN: Could you go through some of the symptoms you’ve had?

Patient D: Yeah. I know one of the key things that I remember was at some point before I went to Mexico and took this drug as a test. I felt I was losing my edge. I’m a photographer and a writer. And I felt like something had happened to me where I had no edge. I couldn’t think critically. And I hated that.

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It was just almost unbearable, to not have the creative side of you active in promoting things. So there was a story in Newsweek, or maybe The New Yorker, about a guy who’d lost his edge. And he was describing me.

Well, after ibogaine, my edge came back! The fact that I can carry on this conversation with you, having full blown Parkinson’s, is a feat in itself. My voice isn’t the same as it always was. My voice has inflection, it has different ranges of emotions. So just be able to communicate.

LN: My mother died of Parkinson’s at age 83. She had it for about 10 years. And during the last few years, she couldn’t do anything. She couldn’t even move. Her hands were like, literally there was no juice in them. There was no electricity, she couldn’t do anything.

Patient D: Dyskinesia. It’s like a fox, he flails around. I can sense it. It’s there. I can feel it within me. But I don’t do it. I’m very fortunate about that.Most Parkinson’s people have a tremor in their hand, their hand just shakes on them, you know, and they always have to stick it in their pocket, or they hide it under a coat. Totally embarrassing, I guess. I have one friend from high school, her husband has Parkinson’s. She’s a wealthy suburban woman who inherited a lot of money, and she’s having to change her lifestyle, from whatever amount of money they can spend each month, because the only drug that works for him, that helps reduce his symptoms, costs $9,000 a month. It’s one that’s a new release; it eliminates some of the symptoms, IF you can afford it.

So, there are no other drugs, except for the classic carbidopa levodopa, which simulates dopamine, but it doesn’t produce dopamine. It just has some effect on your sense of well being and your muscle tone, that calms them down. But other than that, there’s nothing that can help you. They come up with derivatives of this and that, makes me sick. I’ve tried them all. The doctors. I told one doctor what I’ve done and what I’ve experienced. And he says, “Shut up, I don’t want to hear about it. What am I supposed to do with that information?” It’s true. He'd get himself into trouble.

LN: So, do you take any medications now, other than ibogaine?

Patient D: I take a whole host of medications, for blood pressure, for a hiatal hernia, and other conditions I had before Parkinson’s. The main thing that happens with Parkinson’s folk, is they become apathetic–about life, or getting out of bed, or even about moving. They become apathetic and a lot of that sinks into depression right away. And I can experience apathy. I’ve never had any depression, which is kind of amazing. They keep asking me, on a scale of one to 10, are you depressed? And they ask it in varying ways, to see if you’re telling the truth, I guess. But I can’t tell anybody about ibogaine. They just go nuts, the medical field.

LN: Have you shared this with any medical people?

Patient D: Well, there are a couple of doctors in New York that are proposing to the government that what the government needs is a full blown, NIH trial, and they’re not able to get any funding. Look at all the body of proof about ibogaine for opioids. There’s really a large body of verifiable truth. “No effectiveness. It’s not legal in this country. It has no medical uses,” according to the government.

ES: There’s an underground network of providers.

Patient D: Well, I have a list of different symptoms that aren’t normally discussed by doctors. I mean, they don’t tell you about these right away. They do eventually. Okay. These are some of the lesser known functions that are not muscle functions, of the things that happen to Parkinson’s people, that they just can’t tell you (about) because they don’t improve, but I can tell you because I have improved.

Like sleep disorders, depression and anxiety, voice volume, slurred speech. I mean, it was very bothersome when you couldn’t express yourself. Cognitive issues, memory loss, multitasking is something I can’t do anymore. For some reason. I can’t have two things coming at me. I get confused.

So I still have that part of Parkinson’s. I can take care of one thing at a time and follow through and finish it though. They call it orthostatic hypotension which is something I can experience. If you stand up real fast, you get dizzy from that. It’s turned into me actually trying to think of the name now. Lost my sense of balance. Vertigo. I’m learning a new movement technique to counteract it when it happens, because when it happens, I feel like I’m gonna fall over. I haven’t fallen over, but I think I might.

So falling over is the one thing of any illness, where you end up going to the hospital. You hurt yourself. Dystonia, which is muscle contractions of the leg muscles, “restless leg” they call it, but it’s worse than restless leg, like continual.

And the carbidopa levodopa works on me to stop that. So that’s good. The ibogaine doesn’t. They call it bradykinesis— when your face freezes.

LN: I can’t even imagine that. I used to think about it when I saw my mother and I thought it’s like you’re a prisoner inside your own body.

Patient D: Yeah. Kind of like what its like. A prisoner inside your own body.

Apathy and fatigue. Depression and anxiety are one thing, apathy and fatigue are another, entirely separate issue. I can become very apathetic about things unless I get myself jazzed up for something. So sometimes, when I’m in a slump period with Parkinson’s, I don’t feel like doing anything, and I have to push myself through.

So if you lose your sense of edge and you’re wallowing in apathy, it’s a terrible place to be. And I think one of the main benefits that this stuff ibogaine has had on me is mental acuity, so I can still sit and type. I’m getting ready for Dragon Speaking software, for when I can’t type. I don’t drive on the freeway anymore. I can only drive short distances around town because of my eyesight. Parkinson’s affects everything about you. I have terrible seborrhea, like all my skin will just come off — not all of it but just pieces of it dries up and peels off. It’s more embarrassing than it’s painful. Doesn’t bother me. But it bothers the people around me.

And actually, this is the longest I’ve spoken in a long time. I’m tired. It’s something I face every day, but I can deal with it. I’ve got a friend here in town. She can’t even lift the phone to make a phone call. She doesn’t want to. So ibogaine has been a lifesaver for me.

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BEFORE YOU CONSIDER TRYING TO MICRODOSE IBOGAINE YOURSELF, PLEASE BE AWARE THAT THERE IS NO MEDICAL RESEARCH TO GUIDE YOU; “PATIENT D’S” STORY IS ALL WE HAVE. IBOGAINE HAS A HALF-LIFE IN THE BODY AS “NORIBOGAINE” AND SO IF YOU MICRODOSE REGULARLY WITHOUT A BREAK YOU MAY EVENTUALLY EXPERIENCE A FULL DOSE’S EFFECTS, WITH ALL ATTENDANT CARDIAC RISKS. IBOGAINE INCREASES THE “QT” INTERVAL OR GAP BETWEEN HEARTBEATS, AND FOR THOSE WITH CERTAIN CARDIAC CONDITIONS, THAT COULD PROVE FATAL. WE DO NOT RECOMMEND THAT ANYONE TAKE IBOGAINE WITHOUT MEDICAL SUPERVISION.

 
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Ketamine seen as a potential dyskinesia treatment for those with Parkinson's

by David Melamed, PhD | Parkinson's News Today | 19 Oct 2020

Pharmather has entered into an exclusive licensing agreement with the University of Arizona, allowing the company to further develop ketamine as a potential treatment of dyskinesia — involuntary, jerky movements — associated with levodopa use in people with Parkinson’s disease.

The company plans to file an investigational new drug application with the U.S. Food and Drug Administration (FDA) to open a Phase 2 trial of ketamine, an approved anesthetic, later this year.

“We are very pleased to have an exclusive license agreement in place with the University of Arizona to allow Pharmather to advance the clinical program of ketamine in the treatment of Parkinson’s disease, specifically targeting levodopa-induced dyskinesia, a significant clinical unmet need,” Fabio Chianelli, CEO of Pharmather, said in a press release.

Evidence suggests that roughly 50% of Parkinson’s patients receiving levodopa, a mainstay of disease treatment, will develop dyskinesia within four or five years, and an estimated 80% will experience it after 10 to 12 years of levodopa therapy.

Ketamine has also been shown to reduce pain and symptoms of depression when given at lower, sub-anesthetic doses. Researchers at the University of Arizona originally intended to use ketamine as pain reliever for people with Parkinson’s.

When investigators treated five hospitalized patients with low-dose infusions of ketamine, they noticed an easing not only of their pain symptoms, but also their involuntary movements. One patient remained free of dyskinesia for several weeks post-treatment.

This observation led researchers to conduct additional preclinical studies that demonstrated ketamine, given at low doses, relieved abnormally jerky movements in a mouse model of levodopa-induced dyskinesia (LID).

Study data prompted the team to patent this treatment, a process that is ongoing, and to license it to Pharmather in order to advance its clinical development. If approved for dyskinesia, the treatment will also be marketed by the company.

As an FDA-approved treatment, ketamine has a known safety profile in humans, which may speed its potential repurposing as a treatment of LID in people with Parkinson’s.
Pharmather plans to possibly expand ketamine’s clinical development. In addition to being an anesthetic for surgeries or other medical procedures, ketamine is known to be effective in people with chronic pain and treatment-resistant depression.

“With promising results in preclinical models and in Parkinson’s disease patients, we aim to expeditiously advance the ketamine program in Parkinson’s disease to reduce dyskinesia associated with levodopa therapy,” and to advance it to potentially “treat depression and pain associated with Parkinson’s disease and other motor disorders that are prevalent in Multiple sclerosis, Alzheimer’s and Huntington’s disease,” Chianelli said.

A company goal is “ultimately creating a unique pharmaceutical-based ketamine franchise,” he added.

 
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Study to examine the effects of psychedelics in treating Parkinson’s*

University of Maastricht | 2 Dec 2020

Silo Pharma, Inc., a developmental stage biopharmaceutical company focused on the use of psilocybin as a therapeutic, today announced that it has entered into an investigator-sponsored study agreement with Maastricht University of the Netherlands. The research project is a clinical study to examine the effects of repeated low doses of psilocybin and LSD on cognitive and emotional dysfunctions in Parkinson’s disease and to understand its mechanism of action.

Dr. Kim Kuypers, Associate Professor, Department of Neuropsychology and Psychopharmacology at Maastricht University, will serve as Investigator Sponsor for the Phase 2B study. Dr. Kuypers’ main topics of interest are MDMA and psychedelics and their effects on (social) cognition, creativity, hormones, and underlying brain mechanisms.

“The signing of this clinical study agreement represents a significant milestone for the Company as we continue our work to bring novel therapeutics to patients in need,” stated Eric Weisblum, Chairman and CEO of Silo Pharma. “Dr. Kuypers is one of the world’s foremost clinical investigators in the field of psychedelics and has previously evaluated the concept of micro-dosing in her research.”

The Phase 2B study is a human study to be conducted on a sufficient number of patients, the primary purpose of which is to evaluate the safety and efficacy of psilocybin and LSD on patients suffering from Parkinson’s disease. The primary objective of this trial is to investigate the effects of repeated low doses of psilocybin and LSD on well-being and affect (self-rated), emotional and cognitive attention (computer tasks), and biological markers of neuroplasticity. Secondary objectives are to investigate the effects of repeated low doses of psilocybin and LSD on cognitive performance measures of memory and executive functioning, known to be impaired in Parkinson’s disease (computer tasks) and emotion regulation Parkinson’s symptoms, and biological markers of well-being (immune system, cortisol).

“Parkinson’s disease is a progressive nervous system disorder that affects 7-10 million people globally and currently has no cure,” added Mr. Weisblum. “Our goal, in collaborating with Maastricht University and Dr. Kuypers, is to bring hope to those suffering with this terrible disease. We expect to share additional information regarding protocol, ethics submission and initiation of the study as the information becomes available.”

*From the article here :
 
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