Scientists Uncover New Targets For Treating Parkinson’s Disease
Scientists at La Jolla Institute for Immunology have found that people with Parkinson’s disease have a clear “genetic signature” of the disease in their memory T cells. The scientists hope that targeting these genes may open the door to new Parkinson’s treatments and diagnostics.
“Parkinson’s disease is not usually seen as an autoimmune disease,” says LJI Research Assistant Professor Cecilia Lindestam Arlehamn, Ph.D. “But all of our work points toward T cells having a role in the disease.”
“Now that we can see what these T cells are doing, we think intervening with antibody therapies could have an impact on the disease progression, especially early on, ” adds LJI Professor Alessandro Sette, Dr.Biol.Sci., who led the work with Lindestam Arlehamn.
This study was published recently in the journal npj Parkinson’s Disease.
A shifting view of Parkinson’s
Parkinson’s progresses as dopamine-producing neurons in the brain die. Unfortunately, scientists have been unable to pinpoint what causes this cell deaththough they do have a clue: The doomed neurons contain clumps of a damaged protein called alpha-synuclein.
LJI research suggests these clumps may be the kiss of death for dopamine-producing neurons. Sette and Lindestam Arlehamn recently showed that people with Parkinson’s have T cells that target alpha-synuclein early on in Parkinson’s disease.
Researchers find unexpected drug targets
The path to new Parkinson’s therapies
Parkinsons Surveys Clinical Trials And Volunteer Opportunities
PRISM Parkinsons Research Study The PRISM Parkinsons Research Study is evaluating an investigational drug to determine if it might slow down the progression of Parkinsons. and see if youre eligible to enroll.
Pass to Pass Hikes for Parkinsons Pass to Pass is a nonprofit dedicated to raising Parkinsons awareness while supporting hikers with Parkinsons. This group of volunteers offers multi-day backpacking and hiking trips on the Pacific Crest Trail in Washington, Oregon, and California. Participants are being recruited now for these exciting summer 2022 events. For more details and information, visit www.passtopass.org or contact Bill Meyer at 509-991-1212 or
Parkinsons Progression Markers Initiative In an expanded study, the Parkinsons Progression Markers Initiative is currently working to enroll up to 100,000 people with and without Parkinsons. The study team is especially seeking to enroll people diagnosed with Parkinsons in the past two years and who are not yet on treatment, as well as people 60 and older who arent living with Parkinsons but have a risk factor for it . The observational study is also enrolling people with no known connection to Parkinsons to serve as a control group. Learn more here.
Do you have early-stage Parkinsons? The Orchestra Study is a clinical research study to evaluate the use of an investigational medication called UCB0599 in men and women with early-stage Parkinsons. You can learn more and see if you qualify here.
Learn More About Parkinsons Disease
Parkinsons Disease: The Essentials
If youre new to Parkinsons disease and would like a good overview to help you better understand the disease, please view our Parkinsons Disease: The Essentials presentation. Its a great place to get started with reliable and concise information.
The exact cause of Parkinsons is still unknown, but there is an enormous amount of research being done to learn more. This research has led scientists to formulate a number of theories on the cause of this disease.
While there is no definitive test that can be taken to determine whether a person has Parkinsons disease, movement disorder specialists look for symptoms and use brain imaging technology to accurately diagnose Parkinsons.
Even though Parkinsons is classified as a movement disorderand its motor symptoms are the most discussed and well-knownthere are many non-motor symptoms that display in people with Parkinsons as well.
As of today, there is no cure for Parkinsons disease. But there are many ways in which the disease can be treated to make symptoms more manageable.
Living With Parkinsons
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Dosing Starts In Canada In Trial Of Da01 For Advanced Parkinsons
In Parkinsons, nerve cells that make the signaling molecule dopamine are lost in the putamen, an area of the brain that controls movement.
Standard therapies involve boosting dopamine levels, which are abnormally low in Parkinsons patients, using levodopa. This precursor molecule is converted into dopamine in the brain. However, over time, in some cases, levodopa can lose its effectiveness.
Treatment with BRT-DA01, known simply as DA01, involves surgically transplanting dopamine-making nerve cells derived from human embryonic pluripotent stem cells into the putamen. Pluripotent stem cells are a type of cell that can allow for the development of almost any type of human cell needed for therapeutic purposes. The goal is to replace lost cells and provide a regular source of dopamine.
During surgery, patients are under general anesthesia, and a device that injects fluids into the brain is used to deliver the therapy. After surgery, participants will take immunosuppressants for one year to prevent cell rejection.
Earlier this year, the first surgery was performed, marking the closure of the first enrollment in the Phase 1 study . The trial was recruiting up to 12 patients in the U.S. and Canada. Eligible participants ranged in age from 5076, have lived with Parkinsons for five to 15 years, and have received regular levodopa treatment but did not fully respond.
The study locations have not yet been announced.
Next Step: Human Trials
Dr. Kordower told MNT that the results of this study give him great confidence going forward into patients.
Dr. Kordower will be a principal investigator in a clinical trial that he expects to take place in 2023, which will study a specific population of individuals with PD who have mutations in the Parkin gene .
These individuals experience degeneration of the dopamine system. While they experience motor dysfunction typical with PD, they do not develop cognitive decline or dementia. So, that makes the perfect test to see whether cell replacement strategies can be helpful, Dr. Kordower told MNT.
If the trial is successful, larger trials may follow in a broader population of people with PD. However, it is important to note that while the findings from this study are promising, results from animal models do not always translate into human clinical trials.
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Adenosine A2a Receptor Antagonists
Adenosine receptors are promising therapeutic targets for a variety of diseases, including PD . We found two clinical trials that use adenosine A2A receptor antagonists . The V81444 is a small molecular drug for PD treatment in phase I clinical trial, developing by Vernalis Ltd., Kansas, United States . The trial status shows completed in subject recruiting, and the result is unavailable . Moreover, the Vernalis patented V81444 for further trials and commercialization of the drug . Caffeine acts as a selective adenosine A2A receptor antagonist and reduces neurotoxicity by blocking A2A receptors . In 2014, McGill University Health Centre performed the phase III trial of caffeine for PD treatment . The trial result shows that caffeine did not provide clinically efficient improvement of motor manifestations in 60 PD patients . Based on the available data, V81444 might be an effective Adenosine A2A antagonist compared to caffeine treatment. However, the epidemiologic links between caffeine and lower PD risk do not appear to be explained by symptomatic effects .
Cerevance Parkinsons Disease Trial Plan Details
The planned Phase II/III will likely recruit around 110 patients in each of three treatment arms: low-dose CVN424, high-dose CVN424, and placebo, Dubow says. Cerevance will likely power the trial to show a 1.3-hour reduction in OFF time, accounting for a drop-out rate of around 15%, he adds.
Although Dubow did not state the planned length of the Phase II/III, he says the FDA typically requires studies of at least 12 weeks to get an approval.
In a previous, 135-patient Phase II trial, the high dose of CVN424 showed a 1.3-hour reduction in OFF time after four weeks , according to a March 31 press release. CVN424 was well-tolerated, with most common adverse events being nausea, vomiting, and headache in two subjects each.
While the Phase II trial enrolled patients with Parkinsons disease with at least two hours of average OFF time at baseline, the Phase II/III will enroll patients with at least three hours of OFF time, Dubow says. Historically, it has been difficult to show reductions in OFF time for patients with a baseline of less than three hours, he explains.
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Why Does Parkinsons Cause Non
In Parkinsons, brain cells that produce important neurotransmitters, such as dopamine, are gradually lost over time. The main area of the brain that is affected is the substantia nigra a region of the brain that helps control movement. But researchers now know that Parkinsons is much more complex than this. Changes have been found in areas of the brain stem involved in controlling things such as sleep, and in the frontal part of our brain responsible for things like planning and memory. This could explain why there is such a range of symptoms.
Another explanation for the range of symptoms hinges on the role of neurotransmitters in the brain. They have a vital role in controlling both physical and mental health. In Parkinsons, levels of these chemicals are altered causing a range of symptoms.
While changes in dopamine account for many of the motor symptoms of Parkinsons, changes in other neurotransmitters like serotonin may play more of a role in symptoms such as sleep problems, fatigue and depression. And acetylcholine, another neurotransmitter impacted in the condition, is involved in thinking and memory.
Because symptoms can be due to changes in both dopamine and, or, other signalling molecules, medication that is currently used to replace the lost dopamine in Parkinsons often doesnt help with the management of all non-motor symptoms.
What Happens To The Brain During Exercise
What is happening in the brain during exercise? A Neuro Cycle Class, a Pedaling for Parkinsons class, an RSB class, and a DTD class are designed to help the brain rewire for change. During aerobic exercise at higher intensity levels, muscles contract and release a hormone called Irisin. Irisin is called the exercise hormone , releasing into the brain a protein called Brain-Derived Neurotrophic Factor . The presence of this protein is key to maintaining neurons and creating new ones . And what this means for those living with Parkinsons is life-changing results.
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Parkinson’s Disease Symptoms ‘reversed’ By Mini Implant Trial Suggests
A hospital in Bristol is believed to be the first in the world to implant the smallest device into a brain to reverse the symptoms of Parkinson’s disease.
Southmead Hospital surgeons used a tiny deep brain stimulation device to override abnormal brain-cell firing patterns caused by Parkinson’s.
Tony Howells, the first person to receive the treatment as part of a trial, said the impact was “amazing”.
Twenty-five patients have been selected for the trial that concludes next year.
Mr Howells, who had the operation in 2019, said: “Before the operation I went for a walk on Boxing Day with my wife and I got 200 yards from the actual car.
“I had to turn around and go back because I just couldn’t walk.”
“Then after the operation, which was 12 months later, I went on Boxing Day again and we went for 2.5 miles and we could’ve went further.
“It was amazing,” he added.
Currently there is no cure for Parkinson’s disease, which leads to parts of the brain becoming progressively damaged over years.
Symptoms include involuntary shaking of parts of the body, slow movement and stiff and inflexible muscles.
Most people develop symptoms when they are over 50 but about 5% of sufferers first experience symptoms when they are under 40.
Traditional operations for Parkinson’s involve implanting a fairly large battery into the chest with wires run under the skin through to the top of the head.
It then delivers electrical impulses directly to targeted areas of the brain.
Join The Pd Generation Today
PD GENEration is an initiative that offers genetic testing and genetic counseling at no cost for people with Parkinsons disease.
*Please note that not all content is available in both languages. If you are interested in receiving Spanish communications, we recommend selecting both to stay best informed on the Foundations work and the latest in PD news.
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Parkinsons Disease Drug Therapies In The Clinical Trial Pipeline: 2022 Update
Article type: Review Article
Affiliations: Parkinsons Research Advocate, Oxford, UK | Parkinsons Research Advocate, Marlboro, NJ, USA | The Michael J Fox Foundation, Grand CentralStation, New York, NY, USA | Cure Parkinsons, London, UK
Correspondence: Correspondence to: Simon R.W. Stott, Cure Parkinsons, 120 New Cavendish Street, London, UK. E-mail: .
Keywords: Clinical trials, studies, Parkinsons, disease modification, neuroprotection, immunotherapy, inflammation, gene therapy
Journal: Journal of Parkinson’s Disease, vol. 12, no. 4, pp. 1073-1082, 2022
Pd Therapeutic Strategies In Clinical Trials
In , we have classified these therapeutic strategies into 15 types: dopamine receptor agonists, anti–synuclein aggregation therapy, convalescent plasma therapy, cell-based therapy, gene therapy, serotonin receptor partial agonists or antagonists, monoamine reuptake inhibitors, muscarinic and nicotinic acetylcholine receptor agonists, N-methyl-d-aspartate receptor modulators, anti-apoptotic drugs, kinase inhibitors, myeloperoxidase inhibitors, adenosine A2A receptor antagonists, antioxidants/botanical-based medication, and others. depicts the type of drug or therapy, mechanisms, and the current drugs/treatments in PD.
The type of therapeutic strategies, mechanism, and the current drugs/therapies in the clinical trials of PD treatment.
After analyzing the data collected from ClinicalTrials.gov, we identified forty-seven registered interventional clinical trials in phases I, II, and III as new PD therapies based on the current trial status that shows ongoing/updated or discontinued as of 16 June 2021. Among the forty-seven trials, 19 trials in phase I, 25 in phase II, and 3 in phase III
The trial phases and therapeutic strategies in the clinical trials for PD treatment. A pie chart shows the individual percentage of phase I, phase II, and phase III trials to the total. The phase I/II or II/III trials on ClinicalTrials.gov are showed as phase I or II, respectively. A pie chart shows the proportions of each therapeutic strategy to the total PD clinical trials.
Death Rate From Parkinson’s Rising In Us Study Finds
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Scientists Uncover New Targets For Treating Parkinsons Disease
LJI study suggests therapies could stop T cells from attacking brain cells in Parkinsons
LA JOLLA, CAScientists at La Jolla Institute for Immunology have found that people with Parkinsons disease have a clear genetic signature of the disease in their memory T cells. The scientists hope that targeting these genes may open the door to new Parkinsons treatments and diagnostics.
Parkinsons disease is not usually seen as an autoimmune disease, says LJI Research Assistant Professor Cecilia Lindestam Arlehamn, Ph.D.But all of our work points toward T cells having a role in the disease.
Now that we can see what these T cells are doing, we think intervening with antibody therapies could have an impact on the disease progression, especially early on, adds LJI Professor Alessandro Sette, Dr.Biol.Sci., who led the work with Lindestam Arlehamn.
This study was published recently in the journal npj Parkinsons Disease.
A shifting view of Parkinsons
Parkinsons progresses as dopamine-producing neurons in the brain die. Unfortunately, scientists have been unable to pinpoint what causes this cell deaththough they do have a clue: The doomed neurons contain clumps of a damaged protein called alpha-synuclein.
LJI research suggests these clumps may be the kiss of death for dopamine-producing neurons. Sette and Lindestam Arlehamn recently showed that people with Parkinsons have T cells that target alpha-synuclein early on in Parkinsons disease.
About La Jolla Institute
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Light Therapy Trials For Parkinsons
The benefits of a novel infrared light therapy devices to people living with Parkinsons will be evaluated in an international research study involving Flinders University in Adelaide.
Sydney-based medtech company Symbyx last month announced a worlds first randomised control clinical trial to build on promising results from an earlier pilot study.
The company is working with research groups in Adelaide, Sydney and Canada on the first long-term, double-blinded, placebo trial of the technology to assess the effects of light therapy on motor and non-motor skills in Parkinsons patients over a much longer period this year.
Users have reported greater mobility and fine motor skills, as well as improved cognition, including better mood , sleep and even the return of a sense of smell.
The Flinders University trial protocols will broadly follow those currently under investigation in the Parkinsons RCT being undertaken in Toronto, Canada.
Funded and led by The Hospital Research Foundation Group Parkinsons, the principal investigator of the Adelaide trial will be Dr Joyce Ramos, Lecturer in Clinical Exercise Physiology at Flinders University.
Recruitment for the six-month randomised clinical study will commence in coming months, led by The Hospital Research Foundation Group Parkinsons team. Executive director, Ms Olivia Nassaris, says Christmas Appeal and philanthropic donations will fund the trial.