Parkinson's Disease


Parkinson’s disease is a genetic disease that affects 1 in 100 people over the age of 60. It’s a degenerative neurological disease, meaning that over time it causes the death of brain cells, called neurons. This diagnosis is a life-changing event, as it can make even some of the simplest tasks seem impossible to do. However, gene therapy might offer hope for managing symptoms, or even improving the effects of existing medications.

About Parkinson's Disease

Parkinson’s disease causes nerve cells, called neurons, to slowly die. Neurons create a neurotransmitter called dopamine, which is a chemical messenger that is responsible for sending messages from one nerve cell in the brain to another. Critically low levels of dopamine in the brain can negatively affect motor functions. This results in symptoms with typical onset around age 60, such as tremors, trouble starting movements, slow movement, and impaired balance and coordination. People with Parkinson’s disease also face emotional and behavioral changes, including sleeping problems and depression. This makes life with the disease hard on both the people affected and their caregivers. The cause of Parkinson’s disease is still unknown. However, the environmental and genetic factors that cause the disease—and their relationship between each other—are a major focus of research.

Science of Gene Therapy

Although there’s currently no cure for the disease, there are a variety of medications designed to help people manage their symptoms that need to be taken regularly and are adjusted as the disease progresses. The goal of gene therapy is to provide a one-time administration of gene therapy to better regulate levels of dopamine for those who have poorly managed or unmanaged symptoms. Gene therapy is not a cure, but may allow more effective management of symptoms and for longer. Typically, gene therapy introduces a working version of a gene into cells to create key proteins or enzymes. These genetic instructions need to be delivered to the cells using a vector. Vectors are often derived from viruses because they are capable of entering cells to deliver genetic material, such as a working gene. But don’t worry, all viral genes are removed and the vector is modified to only deliver therapeutic genes into cells. For Parkinson’s disease, gene therapy would deliver a vector that has a new functional gene to help cells create enzymes or neurotransmitters that then work together with existing Parkinson’s disease medications to create a stronger result.

As the disease progresses, not only does the brain create less dopamine, it also creates less of the AADC enzyme. Enzymes are molecules that help serve as catalysts for various chemical reactions in our body. The AADC enzyme helps brain cells convert an amino acid called L-DOPA into dopamine. Amino acids are molecules that combine to create proteins. L-DOPA is naturally occurring, or can be provided via an existing Parkinson’s medication. Without the AADC enzyme to help convert it into dopamine, L-DOPA has no effect. One gene therapy approach currently being researched would deliver the DDC gene via a vector to increase the production of the AADC enzyme. The DDC gene would instruct cells to create more AADC enzymes, allowing the L-DOPA medication to then effectively regulate levels of dopamine in the brain.

Pathway to Treatment

Current Treatments

Let’s talk more about existing treatment options for Parkinson’s disease. There is no standard treatment, as every person has their own unique factors relating to their condition (age, mobility level, severity of symptoms, etc.). There are many medications available. However, none yet exist that can reverse the effects of the disease. It is very common for people with Parkinson’s disease to take a variety of these medications at once, in different combinations of doses and times of the day.

One existing treatment is Levodopa, an oral medication. This drug helps to treat patients in the earlier stages of the disease, but has been shown to have waning efficacy over time. As discussed earlier, the medication could potentially be more effective when paired with a gene therapy approach. Some patients with advanced Parkinson’s disease may undergo a procedure called Deep Brain Stimulation, also known as DBS. In the case of DBS, a device implanted in the brain provides electrical impulses, helping the brain control some motor systems. Initial research has shown that patients with a DBS implant would still be eligible for gene therapy.

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Treatment Pipeline

Investigational gene therapies are being researched by Voyager Therapeutics and Axovant. To learn more about any active and recruiting gene therapy clinical trials, visit the ASGCT Clinical Trials Finder. You can find trials for Parkinson’s disease by selecting this in the "diagnosis" field. 

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Eligibility

You may be curious how people with Parkinson’s disease can participate in clinical trials for gene therapy. These trials offer an opportunity to receive an investigational treatment at no cost, while also benefiting the medical community and others who have the disease. If you think that you or a person in your life may be eligible for a clinical trial, it’s a good idea to speak with a movement disorder specialist to learn more and discuss treatment options. However, to participate in a clinical trial, the individual must meet the eligibility criteria, such as age, diagnosis, treatment history, or travel abilities of that particular trial. These requirements may be different for different trials.

Visit the International Parkinson and Movement Disorder Society’s movement disorders specialist directory to find one in your area.

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Get Involved

One way you can take action is by becoming involved with a patient advocacy organization. They are a great way to connect with other families and patients affected by Huntington’s disease. You may also be able to help advocate for research or policies that impact the disease, while also finding a source of support, advice, and helpful information. The diseases may be rare, but you're not alone.

American Parkinson's Disease Association

Michael J. Fox Foundation

Parkinson's Foundation

The Parkinson Alliance

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Download as PDF

Developing A Treatment

How do clinical trials work? Gene therapies take years to go from theoretical concepts, to preclinical trials, to clinical trials, and, finally, into actual treatments that can improve the lives of patients. Here we learn about the process of developing a treatment.

Leukodystrophy

Leukodistrophies are genetic disorders that lead to the deterioration or malformation of the myelin sheath, a fatty insulation that wraps around nerve axons and is essential for proper neuron function. When the myelin sheath is altered it makes it hard for our nervous system to send messages to different parts of our body, which can impair walking, speech, and vision.

2019

ASGCT Policy Summit

November 4 – 6 | Washington D.C.