The Parkinson’s Foundation study PD GENEration: Mapping the Future of Parkinson’s Disease provides genetic testing and counseling that empowers people with Parkinson’s disease (PD) to discover new insights about their genetic makeup and their family’s risks. Its valuable data also connects people to research. But what many may not realize is that PD GENEration is also here to drive research towards a cure.

Next-generation clinical trials for Parkinson’s disease are targeting the genetics underlying the disease. These trials require participants to carry known genetic mutations to test the safety and effectiveness of these new therapies or drugs.  Equipped with knowledge of their mutations, participants in PD GENEration can move science — and potentially a cure — forward by participating in trials that rely upon their unique genetic backgrounds.

How PD GENEration Helped Activate the ACTIVATE Trial

In 2023, the biopharmaceutical company BIAL began a clinical study, nicknamed “ACTIVATE,” of its promising new PD drug called BIA 28-6156. This drug was designed to restore the activity and function of a protein called GCase, which is impaired in people with Parkinson’s who have a mutation in the GBA1 gene. For that reason, the ACTIVATE study needed participants with PD and a confirmed GBA1 mutation.

“Finding enough patients with this mutation is a major challenge,” said Kathleen McKee, MD, MPH, Director of Movement Disorders at Intermountain Medical Center in Salt Lake City, UT. “If patients are not already identified through prior genetic testing, then you are looking at six months to a year to get all your patients through and test them, which is too slow for enrollment.”

Intermountain Medical Center was one of the healthcare sites that BIAL reached out to when it first began recruiting ACTIVATE study participants. Dr. McKee was tasked with finding which people with PD at their medical center had a GBA1 mutation and could be eligible for the study. 

This task was made much simpler as many members of the center’s PD community had already received genetic testing and counseling through PD GENEration. “We were able to look at a spreadsheet and instantly identify all our PD patients who had identified their GBA1 mutation through PD GENEration,” said Dr. McKee. 

With more than 24,000 people globally enrolled in PD GENEration and growing every month, this ease of finding eligible ACTIVATE study participants was likely accelerated for many other collaborating healthcare sites as well. 

In just under a year, the BIAL study met its recruitment goal of more than 230 people with PD and a GBA1 mutation, an impressive feat in no small part due to PD GENEration. With the study designed to monitor BIA 28-6156's effects over a year and a half for each participant, initial results from this study are expected to be released in mid-2026.

Beginning the Path to a Cure

PD affects people in different ways, largely because of the wide range of genetic mutations associated with disease. Through PD GENEration, people with PD can not only better understand their personal diagnoses but also use that knowledge to help support studies investigating treatments designed for their specific PD mutations.

“I’m excited for PD patients to participate in trials unique to their mutation. I think this is how we will start to discover the cure for PD,. We will discover the cure for one genetic mutation, it will help us learn more about the disease overall, and for patients with that mutation it will be life changing,” said Dr. McKee.

Learn More 

The Parkinson’s Foundation works to improve care for people with PD and advance research toward a cure. Learn more with these resources: 

• Discover how we are working to close gaps in knowledge about PD: Advancing Research

• Learn about and enroll in PD GENEration — a global genetics study that provides genetic testing and counseling at no cost for people with Parkinson’s.

• Explore ways to get involved in the Parkinson’s Foundation — from becoming a research advocate to joining a research study.

Preparing for extreme weather is a burden for anyone in the path of a storm or fire. People with Parkinson’s disease (PD) and their caregivers should take these tips into consideration to ensure that all PD-related needs are accounted for when preparing for a hurricane or any other natural disaster:

• Check all your medications. Take inventory of all medications and reorder any that are running low. 
• Write your medication list down. Write down or print a list of all your medications (not just PD medications). Include medication name, strength, times taken and dosages. This customizable medication schedule can help.
• Make a list of your doctors. Make a list of your doctors and their contact information and take it with you if you need to evacuate before a storm.
• Water and food preparedness. Medications may need to be taken with a meal and usually water. Calculate five gallons of water per person per day. Buy enough water and food to last three to five days.
• Order or print your Hospital Safety Guide in the event you need to educate an emergency responder or health care professional about your PD needs. Order one here.
• Have your Medical Alert Card handy. Keep it with you at all times. Print one here.
• Check in with your support network before and after. Arrange for at least one friend or family member to call you during a weather emergency, especially if you live alone.
• Practice anxiety reduction techniques. The stress of possibly losing power or being evacuated could make anyone anxious, but stress can worsen PD symptoms. Download a meditation or breathing app or try to distract yourself by reading a book.
• Know your nearest shelter. Visit the Red Cross website to find yours. Depending on where you live and your PD symptoms, you may qualify for a Medical Special Needs Shelter where you can get additional assistance with basic tasks. 

Preparing for power loss:

• Avoid overheating. If you lose air conditioning, monitor your body heat. Drink more than the recommended nine to 13 cups of water per day. Exercise in the early morning or late afternoon when cooler outside. Know the signs of heat stroke: flushed face, high body temperature, headache, nausea, rapid pulse, dizziness and confusion. If heatstroke is suspected, go to your nearest emergency room or urgent care for treatment.
• Address lightheadedness. Many people with Parkinson’s experience Neurogenic Orthostatic hypotension (nOH), characterized by a drop in blood pressure when going from a seated position or lying down to standing. Exposure to heat can make nOH worse. If you regularly or occasionally experience lightheadedness or dizziness when you stand up, take extra precaution if you lose power and air conditioning by staying hydrated and standing up slowly. 
• Prepare your devices. If you have a deep brain stimulator (DBS), make sure your patient controller is charged. If you use a DUOPA pump, plan ahead to keep your DUOPA cassettes refrigerated. Call your doctor to ask if you should have extra oral medication on hand in case you are unable to use your pump at any point. 

Preparing for an evacuation:

• Write and follow a packing list. Make sure to include all medications, water and snacks.
• Know your community response plan. Learn about your area’s response and evacuation plans before a storm hits. Find your state’s emergency management agency here.
• Take all your medications in their bottles with you. Try to keep them all in one travel bag.
• Take your walker, cane or wheelchair, even if you only use it occasionally.  
• Consider your devices. If you have a deep brain stimulator, remember to bring your patient controller. If your DBS neurostimulator is rechargeable, be sure that your recharger is fully charged and bring it along with the charging dock.

Download or order a Hospital Safety Guide today. Looking for more information about preparing for extreme weather with Parkinson's? Call our Helpline at 1-800-4PD-INFO (1-800-473-4636). 

Biochemist Kevin McFarthing, PhD, remembers everything about his Parkinson’s disease (PD) diagnosis. “I was diagnosed at 4 p.m. on the 10th of December in 2012,” he said. Ever since, he’s been on the trail of a cure, cataloguing potential Parkinson’s therapies as a joint editor of Clinical Trial Highlights, Journal of Parkinson’s and curating the Parkinson’s Hope List, a database of more than 350 ongoing studies.

In the Parkinson’s Foundation Expert Briefing: The Latest Advances in Parkinson’s Research and Treatment, Dr. McFarthing shares the latest advances in research and how participating in clinical studies brings us closer to a cure.

An Urgency for Progress

Parkinson’s is on the rise. A Parkinson’s Foundation-supported study revealed that 90,000 people in the U.S. are diagnosed with the disease every year. By 2040, more than 12 million people worldwide will live with PD. Pharmaceutical companies are invested in speeding a cure. Identifying new Parkinson’s therapies is among top pharmaceutical research and development priorities.

“We all have our own views of what the cure might mean,” Dr. McFarthing said. For some, it might be “a magic bullet to resolve symptoms and restore our abilities back to where we were before.” While others might hope for “a drug that gives another 10 years of symptom-free life.”

The Challenges

Though drug companies are pursuing advanced therapies for Parkinson’s, costs are high and competition for funding is steep. Countless trial medications often fail in the lead-up to a successful central nervous system drug, such as levodopa (the current first-line Parkinson’s therapy, discovered more than 50 years ago).

According to the Tufts Center for the Study of Drug Development, a central nervous system therapy can cost more than $2 billion in research and take nearly 20% longer than other drugs to develop.

Parkinson’s is complex. Symptoms manifest differently in each person, making a one-size-fits-all approach to drug therapy tricky. Research participation is essential to uncover the causes behind the disease and to find new treatments for the symptoms people see — including tremor, rigidity and slowed movements — and the many non-movement symptoms that accompany PD.

Diverse research and continued investment are also essential. Luckily, as Dr. McFarthing points out, “There is a massive amount of work going on.”

Globally, there are more than 100 studies exploring ways to improve various PD symptoms. More than 250 are investigating potential disease-modifying therapies, treatments that could potentially slow, stop or reverse disease progress.

Bringing New Treatments to Light

After identifying a promising new disease treatment through observational, animal or cell studies, researchers seek clinical trial funding and participants. These carefully monitored trials are done in phases — usually testing one active agent against a placebo — to determine safety and effectiveness. Typically, a prospective therapy must successfully pass Phases 1, 2 and 3 before the Food and Drug Administration (FDA) decides whether a company can submit a new drug application.

Treatment studies to watch include:

Dyskinesia (involuntary, erratic, writhing movements) therapies targeting side effects associated with long-term levodopa use:

• Celon Pharma S.A.’s oral, once-daily CPL'36 demonstrated positive Phase 2 results. The drug hinders activity phosphodiesterase 10a enzyme activity, increasing brain levels of certain chemical messengers to improve motor control.  

• After finishing Phase 2B trials IRLAB’s mesdopetam (IRL790) failed to meet primary endpoints. Researchers are continuing to evaluate its treatment potential. The drug blocks dopamine D3 receptor activity, which may be linked to levodopa-induced dyskinesia.

• Phase 1 investigation of Vistagen’s AV-101 is underway. The drug targets malfunctioning N-methyl-D-aspartate (NMDA) receptors. Healthy receptors are key to nerve cell communication in the brain.

• Sinopia Biosciences is expected to begin clinical trials for a preclinical dyskinesia drug candidate SB-0110.

Drugs that maximize “on” time — the period levodopa provides peak symptom control. As Parkinson’s progresses, a person can experience more “off” times. Therapies intended to extend “on” time include:

• Vyalev (Produodopa in Europe), available in the U.S. as of 2024. This new levodopa formulation targets advanced Parkinson’s. A portable pump delivers a steady infusion of medicine under the skin, providing more consistent symptom control. Vyalev may also improve sleep quality, early morning “off” times and other symptoms.

• Tavapadon stimulates select dopamine receptors to improve movement function and reduce side effects. Current dopamine agonists are nonselective and side effects can include compulsive behaviors and visual hallucinations. Tavapadon delivered good symptom control in Phase 3 trials as a standalone medication and when used in addition to levodopa. The manufacturer, AbbVie, plans to submit a new drug application to the FDA this year.

Stem cell research is challenging. It involves brain surgery and, following the implantation of cells, it takes time to see whether symptoms improve. Despite many stem cell studies for Parkinson’s, researchers had not moved beyond Phase 2 until recently:

• BlueRock Therapeutics, a division of Bayer, submitted positive Phase 1 data on bemdaneprocel – cell therapy that aims to replace dopamine-producing neurons lost in Parkinson’s. Based on the data, the FDA granted the drug a regenerative medicine advanced therapy designation, allowing it to move into Phase 3 trials in early 2025.

 Investigational therapies holding promise to stop or slow PD progression include:

• Neurotrophic growth factors, molecules that stimulate nerves to grow. These may benefit people with Parkinson’s. AskBio’s AB-1005, a glial cell line-derived neurotrophic factor (GDNF) delivered directly to the brain, may minimize dopamine loss associated with Parkinson’s.

• Potential neuroprotective benefits of brain-derived neurotrophic factor and cerebral dopamine neurotrophic factor.

• NLRP3 Inflammasone protein inhibitors aim to block activation of inflammatory molecules linked to loss of dopamine in Parkinson’s.

• Potential neuroprotective benefits of nicotinamide riboside, a form of vitamin B3.

Researchers are also exploring ways to prevent buildup of alpha-synuclein protein, the protein that forms toxic clumps, called Lewy bodies, in the brain of people with PD:

• Roche’s Phase 2 studies of prasinezumab, targeted accumulation and spread of alpha-synuclein. The study did not meet its goal, but the company plans to pursue data that potentially shows benefits of prasinezumab in early Parkinson’s.

• Annovis Bio Phase 3 recently concluded studies of buntanetap, a drug that reduces alpha-synuclein production. Buntanetap did not meet the study’s goals. However, the company plans to continue investigating the drug.

• Mutations in the GBA gene (which makes the enzyme glucocerebrosidase, or Gcase) are one of the most common genetic risk factors for PD. Several companies are researching whether compounds that stimulate Gcase activity can improve motor function or offer neuroprotection. 

  • Ambroxyl, a cough medicine used to decrease phlegm, has been shown to increase Gcase activity in people with Parkinson’s. It may clear away toxic alpha-synuclein clumps. A Phase 3 trial is underway.

  • LRRK2 gene mutations are the most common cause of genetic PD. Investigational studies at four companies are exploring how LRRK2 inhibitors might provide neuroprotective benefits. Another five companies are in clinical trials.

Other potential disease-modifying therapies include GLP-1 agonists. Primarily developed to control diabetes, GLP-1 agonists mimic the human glucagon-like peptide-1 (GLP-1) hormone, which controls blood sugar and appetite. Recent GLP-1 agonist studies include:

• Lixisenatide therapy. Phase 2 trial participants with early PD experienced less motor disability progression than placebo at 12 months. However, many participants experienced gastrointestinal side effects.

• Liraglutide showed significant improvement in some non-motor symptoms, but no difference in motor symptoms during Phase 2 study.

• Phase 3 investigation of exenatide showed the drug was safe and well-tolerated but showed no advantage over placebo in Parkinson’s.

• Phase 2 investigations of NLY01, modified exenatide, did not show improvement in Parkinson’s symptoms.

• Researchers are awaiting results of a Phase 2 Oslo University Hospital clinical study exploring the potential value of semaglutide in Parkinson’s.

Building on Hope

The only way to speed the development of treatments that can slow or stop Parkinson’s is through amplified, ongoing funding. The Parkinson’s Virtual Biotech, a partnership between the Parkinson’s Foundation and Parkinson’s UK, is funding 11 new medications and therapies in research and development.

The Edmond J. Safra Accelerating Clinical Treatments for Parkinson's Disease (EJS-ACT PD) Initiative aims to fast-track safe drug testing therapies using multi-arm multi-stage (MAMS) trial designs — a newer, more cost-effective approach.

MAMS trials allow researchers to assess multiple treatments at once against a placebo. Researchers can discover what is working and discard what is not, without dismantling a trial and starting again. The goal is to facilitate a seamless, cost-effective transition to the next phase of trials and bring effective new therapies to market faster. Other Parkinson’s MAMS trials are underway around the world.

“We expect to get more failures than successes because of the nature of what we’re trying to do,” McFarthing said. “But we believe that something will come out of this.”

How to get involved in Parkinson’s research:

1.      Participate in PD GENEration.

2.      Join a Parkinson’s trial or study.

3.      Become a Research Advocate.