Applications of Gene Therapy in the Treatment of Neurodegenerative Diseases

by Valerie Trotter, GCSOM, MBS 2019
Mentored by Michael Bordonaro, PhD

Much like how vaccines, antibiotics, and monoclonal antibodies have revolutionized modern medicine, gene therapy has the potential to do the same. Gene therapy makes medicine more personal than ever by delivering genetic material into a patient to achieve therapeutic results. This approach, though it is still undergoing much research and development, has the potential to offer new treatments for previously incurable diseases. Neurodegenerative diseases are one example of potential candidates for new gene therapy treatments. Many neurodegenerative diseases currently lack options which would slow or stop disease progression, and treatment instead focuses on symptom management. Typically these types of illnesses have a strong genetic component that may be able to be targeted with gene therapy. 

Alzheimer’s disease is one neurodegenerative disease that most people are familiar with, due to the fact that nearly one in nine elderly citizens of the United States are affected by it. It is characterized by symptoms such as memory loss, confusion, and a general mental decline. Build up of amyloid plaques in the brain are believed to be responsible for this disease, and people with a certain genetic variant are more susceptible of developing these plaques. Gene therapy may be able to introduce a protective gene into those suffering from or at risk of Alzheimer’s disease to decrease the likelihood of plaque build up and dispersion. Studies in mice show that such a treatment can both prevent and even reverse plaque build up. 

Parkinson’s disease is another neurodegenerative disease that could be treated with gene therapy. In Parkinson’s, cells in the brain which produce a chemical messenger called dopamine are targeted for destruction. This leads to a loss of motor and cognitive function. Currently, there are a few options to manage the symptoms and replace some of the lost dopamine, but they do not slow or stop disease progression. Delivery of a certain enzyme to slow down the destruction of dopamine through gene therapy is being studied and has shown promising results. Rodent and primate studies with this type of gene therapy have even been able to show an improvement of some motor skills. Gene therapy trials for Parkinson’s disease have even been tested in humans to show that it is a safe potential option for treatment in the future.
           
Canavan disease is one of the more drastic neurodegenerative diseases that gene therapy hopes to treat. There are two forms of this disease: a severe infant form and a milder juvenile form. Those who are afflicted by the more common infant form have a life expectancy of around ten years old, as they progressively lose brain mass and experience many symptoms like cognitive and motor delays, as well as seizures. Those with the juvenile form have normal life expectancies and many patients may have little to no symptoms. Canavan disease results from a mutation which causes an enzyme in the brain to lose activity. Gene therapy attempts to restore the normal function of that enzyme. Studies testing this treatment on rodents has shown that life can be prolonged with use of gene therapy, which is very promising for human patients suffering from Canavan disease.

There is still a lot of research and testing that must be done before gene therapy can become a mainstream treatment option, but so far there are a lot of inspiring results. Gene therapy has the potential to prevent, reverse, and halt diseases which were previously unstoppable. Harnessing the ability to deliver new genetic information gives patients options to manage their health in ways never seen before.