In 2017, Sanofi Genzyme launched a phase 2 clinical trial of a drug designed to target a specific genetic mutation in some patients with Parkinson’s disease. Researchers hoped the drug would slow or even stop disease progression.
Like many before it, the trial yielded disappointing results and the company shut it down in 2021. It was the latest in a string of unsuccessful clinical trials testing disease-modifying Parkinson’s disease drugs.
Although it failed, the Sanofi Genzyme study was different: It was the first to enroll patients with Parkinson’s disease who had a specific genotype and marked the earliest days of precision medicine and gene-specific drug development for the disease.
Once thought to play only a small role in a small number of patients with Parkinson’s disease,
“We’re about to enter this era of precision medicine for Parkinson’s disease, which makes genetic testing important,” said James Beck, PhD, senior vice president and chief scientific officer for the Parkinson’s Foundation.
“A number of companies have clinical trials or are in preparation for clinical trials to test some specific therapies that would depend upon people having a specific genetic mutation,” he said.
Today, at least four clinical trials of drugs that target specific Parkinson’s disease-related gene variants on LRRK2 and GBA are under way, and more are in the pipeline. Whether these drugs will be effective at modifying the course of the disease remains to be seen. First, the trials must enroll enough patients. And therein lies the challenge: Genetic testing isn’t part of routine Parkinson’s disease care and isn’t covered by most insurance policies. Most patients don’t know their genotype.
It’s a significant roadblock to the future of a precision medicine approach that is based on a patient’s individual genotype, which some experts argue offers the best shot at slowing disease progression.
“To enroll in clinical trials for precision drugs people with Parkinson’s disease have to be aware of their genetic status,” said Roy N. Alcalay, MD, chief of the movement disorders division at Tel Aviv Medical Center in Israel and part-time associate professor at Columbia University in New York. “How can a person with Parkinson’s and a LRRK2 mutation join a precision medicine trial for LRRK2 if she does not know she is a LRRK2 carrier?”
Free genetic testing
Previous studies have shown that some genetic variants increase the risk for Parkinson’s disease after exposure to environmental factors such as pesticides. Research has also shown that a patient’s genotype can predict survival time and that certain medications may prove more effective at slowing disease progression in patients with specific genotypes. All of this points to a significant role for genetics in a disorder that is rapidly increasing.
This makes expanding patient access to genetic testing even more important, Dr. Alcalay said, noting that it’s equally important that patients are informed of their genotype, something that doesn’t usually happen in blinded clinical trials.
To that end, Dr. Alcalay hopes a national genetics study he is leading will address access and need-to-know issues. PD GENEration, a project launched in 2019 by the Parkinson’s Foundation, offers patients free genetic testing for seven clinically relevant Parkinson’s disease-related genes.
Testing is done at home or in a nearby clinic and the results are shared with patients during a free genetic counseling session and with site investigators. Patient samples are stored in a genetic data bank that is open to researchers around the world.
“We surveyed clinical trialists in the Parkinson’s disease field prior to initiation of PD GENEration and estimated that over 90% of people with Parkinson’s disease prior to the effort were not aware of their genetic status,” Dr. Alcalay said.
“I think precision medicine in Parkinson’s disease will not happen without PD GENEration or similar efforts.”