While still in the developmental stage, gene and cell-based therapies for people with Parkinson’s disease (PD) hold promise to improve quality of life. Learn how researchers hope these therapies might benefit symptom management and slow disease progression.

This article is based on Understanding Gene and Cell-Based Therapies in Parkinson's, a Parkinson’s Foundation Expert Briefing webinar presented by Roger Barker, PhD, Clinical Neuroscience Professor, John van Geest Centre for Brain Repair, University of Cambridge, U.K. Watch the webinar now.

Scientists studying potential gene and cell therapies for Parkinson’s base their work on the understanding that the disease stems from a genetic predisposition that impacts a protein found in brain cells called alpha-synuclein. In people with Parkinson’s, this protein builds up (or misfolds) into clusters called Lewy bodies. When Lewy bodies amass and spread, it leads to the death of dopamine-producing brain cells. Dopamine helps us move, balances moods and influences our emotional health. Once a significant number of these cells have died, a person begins to show the movement symptoms of Parkinson's, such as tremors, slowing and stiffening.

Current Parkinson’s therapies relieve symptoms by replacing lost dopamine through medication and disease management and lifestyle tools, such as exercise and complementary therapies.

New frontiers in PD therapy research include:

• Improved medications to target the dopamine system and treat dyskinesia (involuntary movements of the face, limbs or trunk) associated with levodopa use.
• Experimental closed-loop deep brain stimulation (DBS), in which a DBS system can learn what's happening in the brain and control stimulation applied to the brain to improve symptoms such as dyskinesia.
• Therapies targeting alpha-synuclein through reducing its production, slowing the build-up, or stopping the spread.

There are also various approaches within investigational gene and cell-based therapies targeting PD. Some of these aim to:

• replace lost dopamine
• rescue dying cells
• regrow dopamine-producing pathways

Ideally, a person with Parkinson’s could benefit from new therapies while still utilizing current treatment options. Each area of research — including those aimed at improving symptoms and gene therapies that seek to help the body help itself — tackles different factors of Parkinson’s. In the near future, a combination of cell and gene therapies along with pioneering medications, surgical advancements and lifestyle management might offer the most comprehensive therapy for people living with Parkinson's.

Examining PD Gene Therapy Approaches

Different companies are pursuing the potential behind various investigational therapies. At the forefront of research are approaches designed to:

1. Regrow the dopamine system. This method injects a gene intended to act as a growth factor, or fertilizer, to stimulate brains cells to regrow the dopamine system.
2. Replace lost dopamine. This method injects a gene that converts existing cells to produce dopamine. These could replace the need for dopamine-replacement medication.
3. Rescue dying cells. New research holds the potential to rescue dying cells, which could offer a path toward disease modification. This type of investigation is designed to interfere with PD and slow progression.

Though still experimental, different strategies have been taken to explore the above types of research over the past two decades with varying levels of success.

Research Aiming to Strengthen the Dopamine Pathway

In 1993, scientists made a pivotal discovery: glial cell line-derived neurotrophic factor (GDNF) — a protein that supports neurons (nerve cells in the brain) — is extremely powerful at regrowing dopamine nerve cells in a lab environment. This led to clinical trials where GDNF was infused into people's brains to try to regrow the dopamine system. The results of these trials are complex, and it is still unclear whether the therapy works.

Another gene therapy program that worked on the same principle was linked to those studies. The program connected neurturin protein (a similar substance to GDNF, though not as powerful) to the AAV2 gene. The investigation studied whether injecting the AAV2-neurturin gene into the area of the brain where dopamine is released would spur cells to take up the gene and promote dopamine fiber growth.

The AAV2-neurturin study went to a double-blind, placebo-controlled trial (participants were randomized, some receiving the treatment while others received a placebo). The study found that:

• At 12 months, there was no difference between those who received neurturin therapy and those who did not.
• At the end of 18 months, people who received the treatment seemed to be doing slightly better, leading investigators to think a successful trial needed more time.

In its second trial, AAV2-neurturin gene was injected into two sites in the brain. After two years, the study showed no therapeutic difference between the trial and placebo groups.

After the GDNF and AAV2-neurturin gene therapies trials, researchers came together to identify what they learned. They concluded such therapies held promise, but recommended future studies take place earlier in the course of Parkinson’s. In the first 1 to 3 years of diagnosis, a person still has several functioning dopamine fibers. These decline rapidly after the first three years. By 5 to 15 years post-diagnosis (the stage most previous trial participants were in) there are few dopamine fibers left.

Today, companies moving GDNF gene therapy trials forward include uniQure and Bayer. Though not gene therapy, Parkinson's UK is pursuing the potential benefits of a protein infusion to boost GDNF levels in the brain.

Can we spur non-nerve cells to make dopamine?

Another PD gene therapy approach is to attempt to infect certain non-nerve brain cells to give them the capacity to make dopamine. There are two main approaches:

• Inject cells to create a synthetic pathway for dopamine in its entirety.
• Give someone enzymes that mediate aspects of the dopamine pathway, along with medication that converts into dopamine.

A ProSavin gene therapy trial relied on a lentivirus as the means to infect cells with pathways that contain the enzymes for making dopamine. Researchers delivered the gene therapy in a single operation on both sides of the brain into the area where dopamine is normally released. They found that using three different doses, delivered in slightly different ways, produced a benefit. However, the benefit was not as effective as DBS and other therapies.

Based on that study, Oxford BioMedica came up with a new gene therapy called OXB-102, which was later bought by Sio Gene Therapies. The study was to have three cohorts of increasing doses, however, the trial was stopped for financial reasons. We cannot draw firm conclusions; however, preliminary research shows the therapy may offer some signs of disease stabilization. Oxford BioMedica now has the license but is not developing the therapy.

Parallel to the above study, U.S.-based Voyager Therapeutics ran a trial using an enzyme associated with making dopamine. Researchers used a similar process — giving different doses to different groups of participants, correctly hypothesizing that giving more gene therapy would induce a bigger response. However, the study was placed on a clinical hold in 2020 by the U.S. Food and Drug Administration when magnetic resonance imaging (MRI) showed unexplained brain abnormalities or changes. That same year, study funding ended to prioritize other research.

• Overall, dopamine gene therapies have yet to be shown to work, but researchers say they continue to hold promise.

On the Horizon: Glucocerebrosidase (GCase) Gene Therapy

A mutated GBA gene (that makes the enzyme glucocerebrosidase) is one of the most common genetic risk factors for Parkinson’s. Up to 10 percent of people with PD have this mutation in one copy of the gene. Researchers believe the GBA mutation can cause enzyme activity to drop, predisposing someone to PD.

A Prevail gene therapy trial currently underway called Propel injects gene therapy into participants with GBA1 Parkinson's. At this stage, the study is evaluating:

• Long-term therapy safety
• Immunosuppression requirements (due to therapy-related inflammation)
• The immune response
• Preliminary effectiveness indicators

Cell Therapies

Every person has about 400,000 to 500,000 dopamine cells. When a person has lost about half of those (200,000 or more) they begin to experience PD movement symptoms. Cell replacement aims to inject new dopamine cells into the brain to replace those that are lost or dying. Such therapy could provide the maximum benefit of dopamine medications with none of the side effects.

Trials have been going on since the late 1980s using human fetal dopamine cells. Around 2007, science developed the capacity to take a human stem cell (a cell that divides indefinitely and can be directed to become any type of cell) and turn it into the type of dopamine cell lost in PD. Allogeneic stem cells are those derived from another human. Autologous stem cells are taken from the person for whom they will be used.

Analysis suggests that younger people with less advanced PD fare better with cell therapy. Tissue preparation prior to implantation, post-graph length of immunosuppression to prevent tissue rejection and long-term follow-up also appear to be important.

Learn More

The Parkinson’s Foundation believes in empowering the Parkinson’s community through education. Learn more about PD and the topics in this article through our below resources, or by calling our free Helpline at 1-800-4PD-INFO (1-800-473-4636) for answers to your Parkinson’s questions.

• Genetics Behind Parkinson's
• PD GENEration: Mapping the Future of Parkinson's Disease
• Join A Study
• Advocate for Research

Parkinson’s disease (PD) affects everyone differently and changes over time. Symptoms can be hard to predict and may fluctuate depending on factors like medication, stress and sleep. The pressure to adapt to changing physical abilities, as well as mood symptoms, such as depression, anxiety and apathy, may be overwhelming at times and lead to feelings of hopelessness. Whether you feel this way and are searching for a way forward or just looking to boost your overall well-being, there are everyday strategies that can help.

Below we highlight ways to feel more fulfilled, foster healthy habits and build empowerment and resiliency — all of which can help you adapt to the challenges of life with PD and improve quality of life.

1.    Find what is important.

For most, meaning in life comes from a combination of connection with others, hobbies, spirituality and work. Parkinson's can cause people to withdraw from meaningful activities and lose those connections — especially if getting to places or doing the things you love are becoming more difficult. This can create a sense of loneliness or even make life feel meaningless.

The first step in restoring meaning is to look at what matters most in life and what you enjoy. For some people, it’s spending time with friends or family or giving back to meaningful causes. Try to:

• Carve out time to think about what you value.
• Take a break from screens and social media to clear your head.
• Focus on spending time with people or experiences that lift you up.
• Start small — focus on little things every day that can add joy and meaning to your life.

2.    Pave the way to healthy habits.

Working gradually to create healthy routines around exercise, diet, sleep, medications and connection with others can help with quality of life. Work towards integrating these healthy habits into your routine:

• Exercise regularly to help you move and feel better.

• Eat a healthy, balanced diet that can provide energy and ease symptoms.

• Create a consistent sleep schedule to give your body the time it needs to repair. 

• Take medications at the same times every day to help keep symptoms under control.

• Schedule daily touchpoints with friends and family to stay connected and engaged.

New habits often take extra effort and planning to take hold — especially if the behavior doesn’t come naturally to you. For some people with PD, forming new habits can be tricky since dopamine — a key part of the reward system — declines over time. Finding ways to cue new behaviors can remind you to stick to your goals. For example, plan to attend a new work out class with a buddy to stay on track.

For help identifying personal goals and any barriers getting in the way of forming healthy habits, consider cognitive behavioral therapy, a type of counseling that focuses on replacing negative thought patterns with positive ones.

3.    Believe in yourself.

You are in charge of your health and well-being. Studies show that believing in your ability to tackle life’s challenges may improve mental and physical health. This belief makes it more likely that you will pursue a goal, put in extra effort to accomplish it and stick with it, even if there are setbacks.

When experiencing self-doubt, let others inspire you. Read books or watch movies about people in similar circumstances and how they coped with their challenges. Reach out to a local Parkinson’s Foundation chapter or your neurologist's office to help find a support group that works for you.

You can also inspire yourself by remembering everything you have accomplished and overcome in the past. People are often more resilient than they believe. Most importantly, give yourself grace — coming up short from time to time is part of being human.

4.    Identify obstacles.

Up to 50% of people with PD will experience some form of depression, while up to 40% will experience an anxiety disorder. Caring for mental health and building emotional resiliency requires addressing PD mood changes — some of which require medication and talk therapy (psychotherapy).

Discuss treatment options with your doctor and look for a counselor or therapist if excessive worry or sadness, lack of motivation or other mood changes begin to interfere with daily life.

If you are trying to get back to an activity you love, write down your goals. What obstacles are getting in your way? Is there a way to simplify or modify an activity? For example, if you love baking but are struggling to follow a complex recipe, try getting out all the ingredients at the start and then putting away each ingredient as you use it. An occupational therapist can help you adapt your environment or find new ways to keep doing the things you enjoy.

5.    Take a team approach.

Whether you have lived with Parkinson’s two years or 10, building a support team can help you live better. When possible, seek expert care and rely on different types of experts to address your needs as they arise. A neurologist, speech-language pathologist, physical and occupational therapist, counselor and other healthcare professionals can offer comprehensive care. Contact the Parkinson's Foundation Helpline at 1-800-4PD-INFO (1-800-473-4636) to find professionals in your community.

Don’t limit your teambuilding to those who care for your health. Living with the challenges of Parkinson’s usually requires an “all hands on deck” approach. Look to your closest connections — people who are invested in the outcome of what you're doing — for emotional support. Connect with others also living with PD, whether in person or online, to unite with people that understand your journey on a personal level.  

Helpful Resources

The Parkinson’s Foundation is here for you. Explore our mental wellness resources now:

• 5 Steps to Living Well With Parkinson’s
• Getting Support
• Parkinson’s Q&A: How do I manage my time and mental health?