Parkinson’s affects more than 110,000 people across Canada and millions of people worldwide. While existing treatments help manage Parkinson’s symptoms, they fall short of slowing or stopping its progression. That’s where disease-modifying therapies (DMTs) come in—an exciting area of research that could transform Parkinson’s care. As research into DMTs advances, preparing the Parkinson’s community to understand what these therapies mean, and how they can affect the course of Parkinson’s is crucial. 

How Parkinson’s affects the brain 

Parkinson’s is a complex condition that evolves over time, which makes it challenging for researchers to study. Everyone loses cells as we age, and that includes brain cells. For someone with Parkinson’s, that loss happens more rapidly. This neurodegeneration, the progressive loss of brain cells that produce dopamine (a chemical that helps regulate your body’s movement), is tied to both the motor and non-motor symptoms of Parkinson’s.  

Researchers suggest a few potential reasons for neurodegeneration in Parkinson’s, including: 

  • Harmful protein aggregates: A protein called alpha-synuclein can misfold and clump up in the brain, damaging neurons in the process. 
  • Inflammation: The brain’s immune system becomes overactive and harms healthy cells. 
  • Low energy in cells: Brain cells lose the ability to make enough energy to maintain function and start to die. 
  • Genes: Some people inherit genetic changes that increase their risk of Parkinson’s.

What are DMTs? 

Disease-modifying therapies, or DMTs, are treatments that focus on stopping or slowing down the processes that cause a disease to get worse. For Parkinson’s, DMT research focuses on targeting neurodegeneration. Currently, we have treatments and therapies that address Parkinson’s symptoms, improving mobility and boosting mood for example, but there is no treatment available that stops or slows down the neurodegeneration process. 

Why are DMTs important? 

The impact of a disease-modifying approach for Parkinson’s treatment would be significant. It would mean: 

  • Slower progression: People with Parkinson’s could enjoy a better quality of life for longer. 
  • Support for care partners: Loved ones and care partners would face fewer hardships as the challenges of advancing Parkinson’s are eased. 
  • Economic relief: Slowing progression could mean reduced health care costs. 

Areas of research for Parkinson’s DMTs 

Researchers are focused on several disease-modifying approaches for Parkinson’s. Here are some of the strategies showing potential: 

Exercise 

Exercise, beneficial to everyone, is one of the most important symptom management tools for people with Parkinson’s. It can reduce stiffness and soreness, while improving strength, endurance, coordination and flexibility. It can also boost mood and reduce fatigue. There are many exercise groups tailored to living with Parkinson’s. Search for local support using Parkinson Canada’s CareFinder. 

Research also shows that exercise might help slow progression of Parkinson’s and may protect your neurons1,2,3,4. Studies suggest exercise might reduce inflammation in Parkinson’s and increase proteins that stimulate cell growth as well5. Exercise can also promote overall mental health and help people stay connected to community – both important parts of living well with Parkinson’s.  

Targeting alpha-synuclein 

Though research on exactly why is ongoing, alpha-synuclein is a protein that misfolds and builds up in the brains of people with Parkinson’s. Researchers think that these alpha-synuclein build ups can disrupt brain cell functioning and impact nearby brain cells. Targeting misfolded alpha-synuclein may protect brain cells from dying. Some treatments targeting alpha-synuclein being investigated include: 

  • Antibodies: These therapies are designed to bind and neutralize harmful alpha-synuclein aggregates (i.e., clumps). 
  • Small molecules: These drugs aim to stop alpha-synuclein from clumping together. 
  • Vaccines: These vaccines could help the immune system recognize and remove alpha-synuclein. 

In late 2024, two pharmaceutical companies reported on results from two Phase 2 clinical trials aimed at slowing the progression of Parkinson’s by targeting alpha-synuclein. For more information, read our Experimental Drugs ORCHESTRA and PADOVA show mixed results blog. 

Gene therapy 

Genetics is thought to cause about 10% of all Parkinson’s cases. Gene therapy involves delivering genetic material to modify or replace genes linked to Parkinson’s. Researchers are exploring: 

  • LRRK2 inhibitors: Reducing activity of the LRRK2 gene to reduce cell damage. 
  • GBA gene therapy: Helping brain cells break down waste, like alpha-synuclein, better. 
  • Glial-derived neurotrophic factor: Helping to protect dopamine-producing neurons from harm and potentially recover after being damaged. 
  • Autophagy enhancers: Restoring function to hindered brain processes that are meant to aid in removing damaged cell components and other harmful substances. 
  • Alpha-synuclein gene reduction: Reducing the activity of genes associated with the overaccumulation of alpha-synuclein with the goal of stopping or slowing neurodegeneration. 

Cell replacement 

Cell replacement approaches aim to replace lost dopamine-producing neurons. Researchers are investigating innovative and promising stem cell approaches for Parkinson’s. To learn more, read our Stem-cell therapies to treat Parkinson’s blog. 

Repurposing existing drugs 

Repurposing therapies that have already been proven safe and approved for other disorders is another approach that holds a lot of potential in Parkinson’s treatment. Since their safety has already been established in clinical trials, they can be fast-tracked for use in Parkinson’s if proven effective. For example, amantadine, originally developed as a flu treatment, was later found to help with Parkinson’s symptoms and is now used to treat dyskinesia. 

Many potential DMTs in current Parkinson’s trials are repurposed drugs. Below are some examples.  

Ambroxol, a cough suppressant, is being tested to enhance GBA activity (a gene associated with glucocerebrosidase, an enzyme that helps maintain cell function) and has advanced to Phase 3 trials. Similarly, GLP-1 receptor activators, initially developed for diabetes, are being studied for their potential ability to improve cell survival, reduce inflammation, and potentially slow Parkinson’s progression. Exenatide, Liraglutide, and Lixisenatide are some examples of GLP-1 receptor activators being investigated.  

Remember, these drugs are all still considered experimental for Parkinson’s and more research is needed before they can potentially become part of an evidence-informed treatment plan. 

The role of biomarkers 

Despite showing promise, developing DMTs for Parkinson’s comes with its challenges. We mentioned the complexity of Parkinson’s – different symptoms, progression rates and underlying mechanisms – as one of the main challenges in developing DMTs for Parkinson’s.  

Lack of reliable biomarkers for Parkinson’s is another significant challenge. Biomarkers allow researchers to identify a condition and observe its response to treatment and therapies. Researchers are beginning to discover possible biomarkers for Parkinson’s which can potentially lead to earlier diagnosis and progression tracking and would help researchers design and test DMTs for Parkinson’s. 

Looking ahead 

Everyone experiences Parkinson’s differently, and many varying factors contribute to its development and progression. Diverse and multifaceted research approaches are crucial as research moves forward. And when DMTs for Parkinson’s become available, matching the right treatment at the right stage of Parkinson’s for everyone will be key.  

The discovery of safe and effective DMTs for Parkinson’s are unlikely to completely replace symptom-managing treatment. Instead, DMTs will likely complement existing medications, such as levodopa, and therapies, such as physical therapy. Learn more about what treatments are currently available for Parkinson’s.  

As researchers continue to make progress, preparing the Parkinson’s community for the arrival of DMTs is equally important. Parkinson Canada is committed to helping individuals understand what DMTs are, setting realistic expectations about their potential, and advocating for equitable access to these treatments when they come available to ensure they can be effectively utilized by those who need them most. By learning about DMTs, including how they differ from symptom management therapies and the impact they could have, people living with Parkinson’s and their families will be empowered to make informed decisions. 

For more information 

Parkinson Canada is committed to funding key research aimed at better understanding Parkinson’s. If you’d like to stay up-to-date on research developments and other Parkinson’s news, you can: 

The dedication of scientists, clinicians, and advocates is a beacon of hope for the Parkinson’s community. While challenges remain, the potential for transformative breakthroughs has never been greater. In the meantime, living well with Parkinson’s is possible with the right treatment, community connections and support. For more information and support, reach out to us at via email or call 1-888-664-1974.   

References
  1. Seo, D. Y., Heo, J. W., Ko, J. R., & Kwak, H. B. (2019). Exercise and neuroinflammation in health and disease. International neurourology journal, 23(Suppl 2), S82. 
  2. Hu, J., Huang, B., & Chen, K. (2024). The impact of physical exercise on neuroinflammation mechanism in Alzheimer’s disease. Frontiers in Aging Neuroscience, 16, 1444716. 
  3. Tomlinson, C. L., Herd, C. P., Clarke, C. E., Meek, C., Patel, S., Stowe, R., … & Ives, N. (2014). Physiotherapy for Parkinson’s disease: a comparison of techniques. Cochrane Database of Systematic Reviews, (6). 
  4. de Laat, B., Hoye, J., Stanley, G., Hespeler, M., Ligi, J., Mohan, V., … & Tinaz, S. (2024). Intense exercise increases dopamine transporter and neuromelanin concentrations in the substantia nigra in Parkinson’s disease. npj Parkinson’s Disease, 10(1), 34. 
  5. Dinoff, A., Herrmann, N., Swardfager, W., Liu, C. S., Sherman, C., Chan, S., & Lanctot, K. L. (2016). The effect of exercise training on resting concentrations of peripheral brain-derived neurotrophic factor (BDNF): a meta-analysis. PloS one, 11(9), e0163037.