Deborah Phippard, PhD, on the Challenges of Evaluating Gene Therapy for Parkinson Disease

“If you're talking about recruiting patients into a study before they've got any clinical symptoms, which is probably where you have your best chance of having an effect, you've got to persuade people to go into what is a maybe a high risk [trial]—so persuading patients to enter that study, I think is challenging.”

Because Parkinson disease (PD) is a highly complex disease with a pathophysiology that is not fully understood, it is not particularly clear what therapeutic targets may be best to address it. This factor alone complicates the development of gene therapy products for the disease. Even if this challenge is overcome, however, and potentially effective therapeutic target has been selected, another challenge arises when companies and institutions have to design clinical trials to test such novel therapeutic products. Indeed, the complexity of the disease natural history and the need to recruit suitable participants for such a trial will both present difficulties.

Recently, CGTLive® reached out to Deborah Phippard, PhD, the chief scientific officer of Precision for Medicine, a clinical research services organization, to learn more about this topic. Phippard pointed out that PD may be more accurately viewed as a group of related diseases rather than a single disease, with different underlying mechanisms causing symptoms in different patients. As such, gene therapy products that target a specific underlying mechanism may be effective in some patients, but ineffective in others. Therefore clinical trial sponsors may need to come up with a diagnostic criteria for eligibility in order to ensure that the therapy is evaluated in patients who are likely to benefit. Another issue arises when determining what stage of disease to treat patients at. Phippard noted that, unfortunately, patients with late-stage disease may be less likely to benefit, and that a preventative approach in patients who have not yet developed symptoms may be ideal. This requires the recruitment of patients who don’t have symptoms, however, which presents substantial challenges for patient identification, willingness of patients to participate, and the selection of measurable end points.