Research Into Better Care
Parkinson’s Australia promotes the best possible quality of life for people with Parkinsons. This section provides evidence-based research to the Parkinsons community on symptom management, and better care options for living well.
A Phase 3 study to evaluate efficacy, safety, and tolerability of ampreloxetine in subjects with primary autonomic failures and snOH with up to 4 weeks of treatment.
18 Aug 2020
At present, stem cell therapy is one of the most promising potential treatments of Parkinsons as it enables renewal of dopaminergic neurons in the substantia nigra possible.
Stem cell therapy is based on cultivating stem cells and differentiating them to grow into dopamine secreting neurons which can be transplanted into the brain. Cultivating stem cells and maturing them requires additional application of growth factors which can induce turour growth after transplantation. Additionally, this method could have difficulties in growing fully matured cells resembling the brain neurons and have short life span.
The invention of nanostructures by a research team led by Professor Ken Yung Kin-lam, Professor of the Department of Biology and Dr Jeffrey Huang Zhifeng, Associate Professor of the Department of Physics at HKBU can stimulate growth of stem cells into miniature substantia nigra like stem cells .
14 Jun 2020
21 May 2020
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Where Is Drug Development Headed
Overall, experts say the Parkinson’s disease field aims to develop therapies that can slow or stop disease progression. Kordower notes several promising gene therapy and stem cell therapy approaches are entering the early stages of clinical development.
Most ongoing PD trials are at the Phase II stage, according to GlobalDatas Clinical Trial Database. While institutions are sponsoring 84 trials of the 133 ongoing Phase II studies , pharma companies are running 44 trials of the 56 ongoing Phase I studies .
As the field awaits results from the slew of ongoing trials, experts agree that the PD trials reading out in the remainder of 2022 could have a substantial impact. These four trials are all very timely, Eidelberg says. The community of movement disorder specialists and neurologists would use these drugs because the indications we’re talking about are really very common.
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Treatments In Phase Iii Trials
What we see in Phase III trials this year is a total of 22 treatments from five different therapeutic categories. Three treatments in Phase III are disease-modifying treatments that have the potential to alter the progression of Parkinsons disease. One is widely used in traditional Chinese medicine, one is a repurposed Alzheimers medication, and the other is a repurposed diabetes medication.
There are also 19 studies in Phase III addressing symptoms of Parkinsons. While the community waits for gains to be made with disease-modifying treatments, improvements in symptom relief are critical for maintaining the quality of life. more personalized treatment plans If the symptom management products in Phase III safely and successfully complete their trials, the medical community will have more tools available to support Parkinsons symptom management.
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The Promising Treatments In The 2022 Parkinsons Clinical Trials Pipeline
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As we know the Parkinsons research community is hard at work to find therapies and treatments to improve the quality of life of Canadians living with Parkinsons and ultimately find a cure. An article outlining the current clinical trials pipeline for Parkinsons was recently published in the Journal of Parkinsons Disease. Here are some of the key highlights. For a refresher on clinical trials and what happens in each phase, here is a helpful FAQ.
As of January 2022, there were nearly 150 Parkinsons therapies active in the clinical trial pipeline:
- 50 products in Phase I
- 65 products in Phase II
- 17 products in Phase III
Most of the drugs in trials are for managing the symptoms of Parkinsons . Developments in disease-modifying treatments the types of treatment that change the course of Parkinsons progression have been slow to emerge. However, in 2022, there are 54 disease-modifying treatments in trial phases, with three graduating to Phase III trials!
Below youll find a brief overview of whats happening in each phase of the trials.
The Promise And Potential Of Stem Cells In Parkinsons Disease
Neurosurgeon Viviane Tabar is co-leading a trial to inject stem cells into the brains of people with Parkinsons disease to restore dopamine levels.Credit: Courtesy of Memorial Sloan Kettering Cancer Center
Neurosurgeon Viviane Tabar has scrubbed in. In front of her is the first participant in a clinical trial to determine whether stem cells can be safely injected into the brains of people with Parkinsons disease. The cells had been frozen, but they are now thawed and sitting on ice, waiting for their moment.
Tabar, a physician-scientist at Memorial Sloan Kettering Cancer Center in New York City, makes an incision in her patients scalp and drills a small hole in their skull. She then uses a brain scan almost like a GPS, she says, to guide her to the putamen a part of the brain in which levels of the neurotransmitter dopamine are unusually low in people with Parkinsons. Once she has confirmed that shes reached the right spot, she injects the stem cells, then repeats the process on the other side of the brain. She hopes these cells will take hold and eventually begin to produce dopamine where otherwise there would be little or none. The surgery itself is minor enough that the patient can go home the next day.
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More On Symptom Treatment And Disease
In 2022, 32 trials will be completed, including three stem cell trials. The decisions about which will move on to the next steps will be captured in the 2023 update. The current research landscape holds much promise. We are eagerly awaiting the results of the 32 trials being completed this year, what trials graduate to the next phases, and what new therapeutic categories will join the pipeline over the course of this year.
References
McFarthing, K., Rafaloff, G., Baptista, M., Mursaleen, L., Fuest, R., Wyse, R. K., & Stott, S. . Parkinsons Disease Drug Therapies in the Clinical Trial Pipeline: 2022 Update. Journal of Parkinsons disease, 12, 10731082.
Parkinson Canada’s mission is to transform the lives of people living with Parkinson’s across Canada. Articles like this represent our commitment to building awareness and providing resources and support for people living with Parkinson’s and their care network.
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The Parkinsons Disease Medication Pipeline
The pipeline for Parkinsons disease medications is extremely crowded these days, with multiple medications at various stages of research development. This is very exciting news for the PD community and is a perfect example of the hope in progress part of our organizations motto. It is thrilling to see the research that is underway, especially the potential treatments that have already made it to the clinical trial phase of development. However, this progress brings with it the welcome challenge of keeping track of all the potential compounds that are in research development! Recently, a review was published in the Journal of Parkinsons Disease which cataloged the 145 compounds that are currently being studied in humans via clinical trials for PD. This is a staggering number and is even more exceptional when you consider the many more compounds that are not quite yet ready for human trials, but are currently being studied in the laboratory in test tubes, cell culture or animal models of PD. The number also does not account for compounds that have been studied in small clinical trials, garnered promising data, and will be studied in larger clinical trials in the near future but are not being tested in clinical trials right now.
Some background on the review
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Exploring Seven Recently Approved Parkinsons Treatments
Remarkably, in the last five years, seven new medications have been approved for the treatment of the motor symptoms of Parkinsons disease , with two approved in 2020. Thats exciting progress! And while it is great to have so many choices, the various options can be confusing so today I will describe these new medications and their uses.
New Medications For Off Time
A number of new medications approved recently are designed to reduce OFF time. These medications fall into two major categories:
- Medications that lengthen the effect of a carbidopa/levodopa dose
- Medications that are used as needed if medication effects wear off
Well give specific examples below. In general, new medications that extend the length of a carbidopa/levodopa dose are used if OFF time is somewhat predictable and occurs prior to next dose. New medications that are used as needed are most beneficial when OFF time is not predictable.
New medications that lengthen the effect of a dose of carbidopa/levodopa
- Istradefylline is an adenosine A2A receptor antagonist which was approved in the US in 2019 as an add-on therapy to levodopa for treatment of OFF time in PD. Unlike many of the other medications, it has a novel mechanism of action and is the first medication in its class to be approved for PD. It acts on the adenosine receptor, which modulates the dopaminergic system, but is not directly dopaminergic. The drug was developed in Japan and underwent clinical trials both in Japan and in the US.
- Opicapone is a catechol-O-methyltransferase inhibitor that is taken once a day. It was approved in the US in 2020 as an add-on therapy to levodopa for motor fluctuations.
New formulations of levodopa designed to be used as needed if medication effects wear off
Other medications used as needed if medication effects wear off
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Living Well With Parkinson’s
While medication and DBS surgery are the most effective treatments for PD, individuals often choose to delay these treatments because of their adverse side effects. Until a therapy is developed that can halt the progression of PD, there is a significant need for strategies that provide symptom relief without causing negative side effects.
Diet, Exercise, and Stress Reduction
Findings from several studies suggest that exercise has the potential to provide relief from certain PD symptoms. Anecdotally, people with Parkinsons disease who exercise typically do better. However, many questions remain. Among them is whether exercise provides a conditioning effect by strengthening muscles and improving flexibility or whether it has a direct effect on the brain.
In an NINDS-funded trial comparing the benefits of tai chi, resistance training, and stretching, tai chi was found to reduce balance impairments in people with mild-to-moderate PD. People in the tai chi group also experienced significantly fewer falls and greater improvements in their functional capacity.
Technologies that Improve Quality of Life
George C Cotzias Md Memorial Fellowships: Academic Year 2023
Deadline for Letter of Intent Dec 2022
Dr. George C. Cotzias was a pathfinder in the pharmacologic exploration of brain function and in the treatment of Parkinsons disease with levodopa. The American Parkinson Disease Association established the George C. Cotzias Memorial Fellowship to honor the memory of the late Dr. Cotzias and to stimulate young neurologists to follow his leadership.
A Cotzias applicant must be a physician who is licensed to practice medicine in the US and who is completing, or has completed, training in a clinical discipline concerned with disorders of the nervous system . Applicants must be a US citizen or permanent resident.
One hundred thousand dollars will be awarded each year for salary and research expenses for three consecutive years , provided that the required conditions are met to the satisfaction of the APDA Scientific Advisory Board and the APDA Board of Directors.
The applicants will receive notification of the decision in July 2023. The APDA grant year runs from September 1 to August 31.
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Uniting Research And The Pd Community
We are committed to understanding Parkinsons from the perspective of the PD community, including people living with PD, those who care for them, researchers, healthcare professionals and research advocates.
With more than two decades of work in patient engagement that has impacted the lives of people affected by Parkinsons through prioritizing research, we match researchers with people in the PD community to help improve studies. Learn more about engaging in Parkinsons research.
Parkinsons Disease Diagnosis And Prognosis
A Parkinsons disease diagnosis cannot be determined by a single test but is rather assigned based on a patients medical history, symptoms, and a series of neurological and physical exams. Each patients Parkinsons disease prognosis is different, as the disease is unique to each person. While all patients will experience some degree of motor dysfunction, the severity and course that the disease takes may differ from person to person.
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Treatments In Phase Ii Trials
Another strategy in the therapeutic research space is drug repurposing. This is when an existing medication for one condition is repurposed to treat an entirely different condition. Working with repurposed medications comes with many advantages including understanding its general safety. Repurposing an existing medication, rather than starting from scratch, typically requires fewer tests for safety as the drug has already met these requirements. This can reduce costs and speed up the process through the clinical trial pipeline. It can also lead to faster approvals, getting much-needed treatments into the hands of people with Parkinsons as soon as possible. There are a total of 74 therapies in Phase II trials and 44% are repurposed medications.
One exciting takeaway from Phase II trials this year is the progress made with stem cell therapies. While there are nine stem cell therapies being explored in Phase I, two stem cell therapies graduated to Phase II trials this year! Moving into Phase II means these treatments are being administered to a larger group of people to monitor their effectiveness and further evaluate their safety.
Treatments In Phase I Trials
As Parkinsons researchers work toward more precision medicines, they benefit from a wide range of therapeutic categories & tools to experiment with. Therapeutic categories refer to all the different categories of research focuses, like stem cells, antioxidants, and gene targeting, for example. With trials spanning more than 15 therapeutics categories in the Phase I pipeline, it has a broad range of focuses. Making discoveries in more therapeutic categories means we can one day provide access to personalized treatment solutions based on the specific causes and symptom presentation of each person living with Parkinsons.
There are 50 treatments in Phase I trials this year with about a 50/50 split between symptom-relieving products and disease-modifying treatments. Half of the treatments in Phase I are new discoveries as the result of pathfinding research. This is when researchers use insights from existing medications to seek out related products that warrant exploration.
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Studies Show Promising Results
“Considering the ability of MSCs to secrete neurotrophic factors, modulate inflammation, and possibly even act as mitochondria âdonorâ, it comes as no surprise that there is a lot of interest in the use of MSCs in the treatment of Parkinsons Disease, and a multitude of animal studies has shown promise. Treatments have resulted in improvement of motor function, protection of the nigrostriatal system, and improved striatal dopamine release in several studies using toxic lesion rodent models of Parkinsons Disease. Similar effects were reported with umbilical cord-derived MSCs with or without prior differentiation. For example, a recent study reported improvement of motor function, reduced microglial activation, and decreased loss of TH immunoreactivity, associated with local production of trophic factors.
Learn more about DVC Stem’s protocol for Parkinson’s Disease here:
References:
Venkataramana, N. K., Kumar, S. K. V., Balaraju, S., Radhakrishnan, R. C., Bansal, A., Dixit, A., ⦠Totey, S. M. . Open-labeled study of unilateral autologous bone-marrow-derived mesenchymal stem cell transplantation in Parkinson’s disease. Retrieved from https://www.sciencedirect.com/science/article/pii/S1931524409002205#!
Unified Parkinson’s Disease Rating Scale. . Retrieved from https://www.sciencedirect.com/topics/medicine-and-dentistry/unified-parkinsons-disease-rating-scale
About the author
Editorial Note On The Review Process
F1000 Faculty Reviews are commissioned from members of the prestigiousF1000 Faculty and are edited as a service to readers. In order to make these reviews as comprehensive and accessible as possible, the referees provide input before publication and only the final, revised version is published. The referees who approved the final version are listed with their names and affiliations but without their reports on earlier versions .
The referees who approved this article are:
- Fredric P. Manfredsson, Parkinson’s Disease Research Unit, Department of Neurobiology, Barrow Neurological Institute, Phoenix, Arizona, USANo competing interests were disclosed.
- Tipu Z. Aziz, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UKNo competing interests were disclosed.
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What Kinds Of Genetic Research Is Being Done
Researchers are investigating genes that code proteins responsible for producing dopamine. By increasing the amount of dopamine in the brain, Parkinson’s symptoms can be minimized if not prevented.
What other treatments are being researched?
- Drug treatments. Researchers are investigating drugs that block the action of glutamate, an amino acid that destroys nerve cells, as well as the role of the antioxidant coenzyme Q-10 in slowing the progression of Parkinson’s disease.
- Neural growth factor. Preliminary studies have shown that neural growth factor revives the dormant cells needed to produce dopamine, dramatically improving symptoms.
- Deep brain stimulation. Research is underway to better understand how deep brain stimulation works in Parkinson’s disease. Researchers are also studying improved ways of stimulating the brain.
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Sidebar: Advances In Circuitry Research
The brain contains numerous connections among neurons known as neural circuits.
Research on such connections and networks within the brain have advanced rapidly in the past few years. A wide spectrum of tools and techniques can now map connections between neural circuits. Using animal models, scientists have shown how circuits in the brain can be turned on and off. For example, researchers can see correlations between the firing patterns of neurons in a zebrafishs brain and precise behavioral responses such as seeking and capturing food.
Potential opportunities to influence the brains circuitry are starting to emerge. Optogenetics is an experimental technique that involves the delivery of light-sensitive proteins to specific populations of brain cells. Once in place, these light-sensitive proteins can be inhibited or stimulated by exposure to light delivered via fiber optics. Optogenetics has never been used in people, however the success of the approach in animal models demonstrates a proof of principal: A neural network can be precisely targeted.
Thanks in part to the BRAIN Initiative, research on neural circuitry is gaining momentum. The Brain Research through Advancing Innovative Neurotechnologies Initiative is accelerating the development and application of new technologies that enable researchers to produce dynamic pictures of the brain that show how individual brain cells and complex neural circuits interact at the speed of thought.
NIH Publication No. 15-5595
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