NOVEL MICRO-RNA THERAPY FOR TREATMENT OF DRAVET SYNDROME, A PEDIATRIC ORPHAN DISEASE

Dravet syndrome (DS), also known as severe myoclonic epilepsy of infancy (SMEI), is a genetic and rare form of treatment-refractory epilepsy that begins in infancy. DS incidence is estimated at 1/30,000 with about 20,000-40,000 patients worldwide. The long-term prognosis for DS patients is poor, including cognitive impairment, behavioral problems, and a high incidence of sudden death in childhood.

Dr. Schaefer and colleagues have discovered that the micro-RNA, miR-128, is a master regulator of neuronal excitability and motor function. Neuron-specific miR-128 deficiency in mice invariably resulted in seizure-induced death (Fig A) and could be rescued by ectopic miR-128 expression (Fig B). In addition, ectopic expression of miR-128 was also able to rescue different classes of chemically induced seizure in a mouse model.

These findings suggest that miR-128 can be used as a novel treatment for patients suffering from severe treatment-refractory epilepsy, such as DS, as well as other neuronal hyper-excitability syndromes such as Parkinson’s associated dyskinesia.

Current Development Status

• Preclinical proof-of-concept studies underway to validate modes of administration of miR-128 in various mouse models of Dravet syndrome as well as generalized epilepsy models; expected completion Q42014

Applications

• Dravet syndrome
• Treatment-refractory epilepsies
• Parkinson’s associated dyskinesia

Advantages

• miR-128 regulation of therapeutic targets modulated by approved anti-epileptic drugs increases its validity as a potential treatment for epilepsy
• miR-128 control of multiple key signaling pathway regulators of neuronal excitability
  broadens its potential therapeutic benefit to a range of hyper-excitability syndromes of divergent etiologies including treatment-refractory syndromes with increased safety and efficacy
• miR-128 functions with strict dose-dependency increasing it safety profile and allowing titration of therapeutic dosage

Publications

• Chan Lek Tan et. al. “MicroRNA-128 Governs Neuronal Excitability and Motor Behavior in Mice.” Science. 342(6163): 1254-1258

Patent Status

• International Application PCT/US2014/062664 filed October 28, 2014
• Status: Published. International Publication No. WO 2015/066034

Contact Information

Lisa Placanica, PhD
Business Development Director
Mount Sinai Innovation Partners  |  Icahn School of Medicine at Mount Sinai
Phone: 646.605.7325