Expanding the Potential to Treat Alzheimer Disease With RNA Therapeutics: Sharon Cohen, MD, FRCPC
The medical director of the Toronto Memory Program at the University of Toronto gave clinical perspective on the promise of mivelsiran, an investigational RNA interference therapeutic, and the idea behind using RNA therapies to treat Alzheimer disease. [WATCH TIME: 5 minutes]
WATCH TIME: 5 minutes
"Going upstream is very attractive to myself, where I'm very prevention-minded... it's very exciting to think we can go into the brain and shut off production of proteins that we think are involved in disease generation."
RNA therapy is a term used to describe the use of RNA-based molecules to modulate biological pathways to cure a specific condition. Once the nucleic acid chemistry and the delivery method are established, the production of RNA-based drugs for a new target can be achieved in a relatively short period. The general public is mostly aware of messenger RNA therapy, a subcategory of RNA therapy, that was influential in developing novel vaccines used to combat coronavirus disease 2019.
To date, there are no approved RNA therapies to treat Alzheimer disease (AD), the most rapidly growing neurodegenerative disorder worldwide. One investigational agent, mivelsiran (Alnylam Pharmaceuticals) is currently being evaluated in an ongoing, phase 1 study (NCT05231785) that features a single-ascending dose and multiple-ascending dose portion. Mivelsiran, otherwise known as ALN-APP, is an intrathecally administered RNA interference therapeutic designed to lower levels of amyloid-ß (Aß) peptide by reducing upstream production of amyloid precursor protein (APP).
Data presented at the recently concluded 2024 Alzheimer’s Association International Conference (AAIC), held July 28-August 1, in Philadelphia, Pennsylvania, showed that 50 mg and 75 mg doses of mivelsiran were well tolerated and produced robust, durable reductions in cerebrospinal fluid levels of soluble APP and downstream Aß42 and Aß40. Led by Sharon Cohen, MD, FRCPC, these interim results supported the further evolution of this agent in patients with AD or cerebral amyloid angiopathy.
Cohen, a behavioral neurologist and medical director of the Toronto Memory Program at the University of Toronto, sat down with NeurologyLive® after the meeting to discuss the mechanism of action of mivelsiran and how it differs from traditional therapies that focus on clearing amyloid plaques. In addition, she discussed the limited use of RNA therapies to treat central nervous system disorders, the barriers clinicians have faced, and the need to ensure no off-target effects.
