08 May, 2018 New Preclinical Data Demonstrating CNS Delivery of RNAi Therapeutics
We presented initial data demonstrating delivery of nove small interfering RNA (siRNA) conjugates to the central nervous system (CNS) at the TIDES: Oligonucleotides and Peptide Therapeutics 2018 Annual Meeting, being held May 7-10, 2018 in Boston, MA.
In a rat preclinical study, a single intrathecal injection of a novel siRNA conjugate resulted in broad distribution across the brain and spinal cord regions. Robust and highly durable silencing of a disease target gene transcript was seen in all key anatomical regions of the brain and spinal cord. Specificity of the silencing effect was confirmed with a second siRNA conjugate targeting an independent gene transcript ubiquitously expressed in the CNS. The novel siRNA conjugates utilize Alnylam’s enhanced stabilization chemistry (ESC) platform with further modifications to enable broad CNS delivery and efficient uptake in neuronal cells.
RNAi therapeutics have the potential to prevent or reverse neurodegenerative diseases caused by dominantly inherited genes, such as in Alzheimer’s, Huntington’s, Parkinson’s, and amyotrophic lateral sclerosis (ALS), where there are limited to no treatment options. We plan to complete selection of our first CNS-targeted development candidate (DC) in 2018, and then expect to file our first investigational new drug (IND) or IND equivalent in late 2019/early 2020, with the potential for one or more INDs per year thereafter.