Sirna Therapeutics Launches Program to Treat Diabetes with RNAi Technology
Thursday January 6, 7:33 am ET
Early Preclinical Research Shows Ability to Silence PTP-1B Expression
BOULDER, Colo., Jan. 6 /PRNewswire-FirstCall/ -- Sirna Therapeutics, Inc. (Nasdaq: RNAI - News) announced today that early preclinical research has shown promising results for the application of RNA interference (RNAi) technology in the treatment of diabetes. Preclinical studies of Sirna's systemically delivered short interfering RNAs (siRNAs) at a dose of 30 mg/kg in mice demonstrated a 72% reduction of PTP-1B (phosphatase 1B), a validated target in diabetes that is associated with insulin resistance.
As an intracellular cytoplasmic protein, PTP-1B is a difficult-to-reach target for small molecule drugs and biologics. The catalytic pocket of the enzyme is large, making it difficult to synthesize a small chemical inhibitor. Further, due to its large family of congeners, specificity is difficult to obtain by small molecules. These developmental challenges make this target uniquely suitable for an RNAi approach.
Sirna's ground-breaking work on siRNAs to treat chronic infection by hepatitis B and C viruses has led to the demonstration of robust and reproducible in vivo siRNA efficacy in the liver. IV dosing at 3 mg/kg of Sirna's formulated and stabilized siRNAs targeting HBV RNA resulted in a 1.7 log reduction in viral titers for at least 7 days in a mouse model of HBV replication. Pharmacokinetic studies have shown that 30% of the administered siRNA gets into hepatocytes. The technology pioneered in this work to efficiently deliver systemically administered stabilized siRNAs to the liver now enables Sirna to address other liver associated disease indications such as diabetes.
Sirna's stabilized siRNA technology utilizes the cell's endogenous RNA interference pathway to down-regulate diseases associated with unwanted gene expression. Due to the interaction with a protein mediated endogenous pathway, siRNA molecules are far more potent than oligonucleotides which function through "antisense" mechanisms. The inherent high potency of the siRNA molecules coupled with Sirna's efficient liver delivery technology result in increased in vivo efficacy at far lower doses than are typically reported with "antisense" molecules. A safety study conducted in monkeys with Sirna's formulated and stabilized siRNAs has shown no adverse effects at doses expected to be efficacious in clinical trials.
Roberto Guerciolini, MD, Senior Vice President and Chief Medical Officer of Sirna Therapeutics, commented, "The demonstration of a significant knockdown of PTP-1B by a clinically viable route of administration represents a promising start for the development of an RNAi-based treatment for Type II diabetes. The high potency, specificity and chemical structure of siRNAs may eliminate the toxicity and adverse events commonly seen with small molecule and other oligonucleotide approaches. Additionally, Sirna's proprietary chemistries and organ-specific delivery technologies are critical components for the successful development of an innovative therapy for this unmet medical need. We expect that after conducting additional studies to optimize siRNA chemistry and delivery efficiency, we will be able to initiate clinical trials in 2007."... |
