University of Pittsburgh School of Medicine researchers are leading the second arm of a trial, now recruiting participants, that will use gene therapy to assist in the easing of tremors and mobility symptoms in Parkinson’s disease patients. The therapy’s goal is to prolong the efficacy of levodopa, a drug used for the treatment of Parkinson’s that increases the production of a critical enzyme that converts levodopa into dopamine.
Parkinson’s involves the malfunction and death of vital neurons, primarily those in an area of the brain called substantia nigra. Some of these neurons produce dopamine, a chemical that sends messages to the area of the brain that controls movement and coordination. As PD progresses, the amount of dopamine produced decreases, leaving patients unable to control movement. Levodopa can replace the faulty dopamine for a while, but ultimately loses its efficacy. Subsequent increases in dosage is not always an option, as they may lead to disabling side effects.
“Less dopamine is made as the neurons degenerate, and one reason is that there is a decrease in an enzyme needed to turn levo-dopa into dopamine,” Dr. Richardson MD, PhD, an assistant professor of neurological surgery, Pitt School of Medicine, director of Epilepsy and Movement Disorders Surgery at UPMC, and the principal investigator of the Pitt arm of the trial, said in a news release. “By inserting the gene for this enzyme into cells in a specific part of the brain, we hope to make levo-dopa treatment more effective for a longer period of time.”
Gene therapy consists in the delivery of nucleic acid polymers into a patient’s cells through an innocuous virus, known as adeno-associated virus-2, carrying a specific gene that inserts the enzyme — aromatic L-amino acid decarboxylase (AADC) — into neurons. When inside neurons, cellular mechanisms are triggered to increase the production of AADC.
To deliver the therapy, Dr. Richardson will insert a catheter through a small hole in a patient’s skull directly into a brain area affected by Parkinson’s disease, called putamen. The gene therapy will be infused for several hours, after which the catheter is removed and the skull repaired.
Different dosages of the infusion will be evaluated in the trial. Up to 20 patients at two different research sites, San Francisco and Pittsburgh, will be followed for up to three years so specialists can reassess the status of their disease and medication.
Krystof Bankiewicz, MD, PhD, of the University of California, San Francisco, is the principal investigator of the trial, sponsored by Voyager Therapeutics. Dr. Bankiewicz led a previous trial that demonstrated the gene therapy it safe to administer.
Potential eligible participants must be age 40 to 70 years, have had the disease for more than five years and have been taking levodopa for a minimum of three years. More information about the trial is available by calling Patricia Porter at 412-648-8983, or by emailing her at Porterpm2@upmc.edu.