Regulatory Pathways and Clinical Trials for Gene Therapy in Parkinson Disease: Michael Kaplitt, MD, PhD

WATCH TIME: 5 minutes

"Another issue with gene therapy is choosing the proper patient that might be best for a particular gene therapeutic. Then [figuring out] how do you deliver that gene therapy to the brain, most of the patients to date have had that done surgically."

In the current realm of treatments for Parkinson disease (PD), clinicians and patients living with the disease highlight the need for more innovative approaches to address the progressive decline in dopamine network function from the condition. As a promising avenue, gene therapy has emerged to offer the potential for sustained restoration of neuronal function by introducing genetic material to regulate dopamine levels and improve dopaminergic signaling.¹ Thus, the clinical gene therapy trials in progress for PD are primarily aimed towards enhancing dopamine production enzymatically and reinstating the integrity of the nigrostriatal pathway.

Despite the potential of gene therapy for PD, substantial challenges impede its translation into clinical practice. The blood-brain barrier presents an obstacle for this since it impedes gene delivery into the central nervous system (CNS) unless it is directly administered. Modified vectors, both viral and non-viral, are in development to enhance delivery efficiency to target these locations in the CNS; however, the limited approved gene therapy approaches for CNS diseases like PD reflect the ongoing safety concerns associated with these viral vectors.² To combat this, there has been an increasing focus on developing alternative non-viral biomaterial vectors to mitigate these safety risks in CNS disorders such as PD.

Michael Kaplitt, MD, PhD, professor of neurological surgery and vice chairman for research in the department of neurological surgery at Weill Cornell Medicine, recently sat down with NeurologyLive^® in an interview to discuss the regulatory barriers that exist for the approval of gene therapies, and how recent approvals in other neurological disorders have influenced the pathway for PD treatments. He also talked about the challenges associated with conducting long-term safety studies for gene therapies compared with conventional drugs. In addition, Kaplitt spoke about how patient selection and delivery methods can impact the effectiveness and feasibility of gene therapy for PD.

REFERENCES
1. Van Laar AD, Van Laar VS, San Sebastian W, et al. An Update on Gene Therapy Approaches for Parkinson's Disease: Restoration of Dopaminergic Function. J Parkinsons Dis. 2021;11(s2):S173-S182. doi:10.3233/JPD-212724
2. Puhl DL, D'Amato AR, Gilbert RJ. Challenges of gene delivery to the central nervous system and the growing use of biomaterial vectors. Brain Res Bull. 2019;150:216-230. doi:10.1016/j.brainresbull.2019.05.024