CNS diseases affect millions of people worldwide and leave clinicians with limited treatment options. Small nucleic acid drugs, including siRNA, miRNA and ASO therapies, act at the genetic level, which gives them a way to address the cause of these disorders rather than the symptoms downstream of it. Prisys Biotechnology supports RNA therapeutic development in this area.
ALN-APP: siRNA Against Amyloid Precursor Protein
ALN-APP is an RNAi therapy that targets amyloid precursor protein (APP), a protein central to AD and CAA. Alnylam is developing it with Regeneron, and it is the first clinical-stage project to use Alnylam's proprietary siRNA conjugation platform for CNS delivery. After a single dose, ALN-APP has shown rapid and sustained reduction of APP-related biomarkers in cerebrospinal fluid (CSF) of early AD patients, which supports the feasibility and efficacy of RNAi therapy for CNS diseases.
DTx and the FALCON Platform
DTx is an RNA therapy company that develops siRNA therapies for neuroscience indications on its FALCON platform. Novartis acquired DTx for $1 billion, including $500 million upfront and $500 million in milestone payments. DTx has a potential therapy for Charcot-Marie-Tooth disease type 1A (CMT1A), a rare neuromuscular disorder, and two preclinical programs for other CNS diseases in its pipeline. The FALCON platform combines natural fatty acids with siRNA to improve cellular uptake and biodistribution, which allows FALCON-modified siRNA to silence disease-causing genes in tissues beyond the liver.
BIIB080: An ASO Against Tau
BIIB080 is an ASO therapy that targets tau protein, a major contributor to AD and other tauopathies. Ionis is developing it in partnership with Biogen, and it is the first gene silencing therapy to be tested in clinical trials for dementia and AD. After 24 weeks of treatment, BIIB080 showed good tolerability and a significant reduction of total tau and phosphorylated tau levels in CSF of mild AD patients. Targeting tau protein may slow the progression of AD and other tauopathies.
These programs show what small nucleic acid drugs can do in CNS disease. Compared with antibody drugs, small nucleic acid drugs allow faster target screening, show higher development success rates, and act more directly. For patients with CNS disease, that combination may mean more effective and longer-lasting treatment.
NHP Models for CNS Drug Programs
As a preclinical CRO, we provide NHP disease models for CNS drug research and development, and we have established models for indications including AD, ALS, HD, FTD and MS. We evaluate the efficacy and safety of small nucleic acid drugs in these models using established technologies and methods. Study designs are adapted to the specific needs of each client.
We work with biopharmaceutical companies developing RNA therapies for CNS diseases. To discuss a CNS program, visit www.prisysbiotech.com or contact the team.
