INSULIN-LIKE GROWTH FACTOR-1 FOR PHELIN-McDERMID SYNDROME, A RARE AUTISM-RELATED SYNDROME

Phelin-McDermid Syndrome (PMS) is a rare genetic syndrome, with a wide range of severity of symptoms, including intellectual disabilities, sleep disorders, and seizures, as well as motor and vocalization symptoms. PMS is caused by disruption of the SHANK3/ProSAP2 gene on the terminal of chromosome 22. Approximately 600 cases are known worldwide, but numbers are expected to increase as new genomic testing methods have made clinical testing more widely available.

Dr. Joseph Buxbaum and colleagues demonstrated that Shank-3 deficient mice benefit from IGF-1, with improvement of deficiencies in adaptation of nerve cells to stimulation, a key part of learning and memory.

Current Development Status

• Ongoing phase I studies, with measures of improvement in motor skills, vocalization, and other outcome-related parameters.  Unblinding of study expected 2H 2014

Applications

• Phelin-McDermid Syndrome
• Possible broader application to other Autism Spectrum Disorders

Advantages

• IGF-1 is approved for short stature children and has a proven safe profile in pediatric populations
• IGF-1 and its N-terminal peptide {(1-3) IGF-1} both have potential to ameliorate certain symptoms associated with PMS and other related disorders
• IGF-1/mescasermin (Increlex®) is administered intravenously, and the recombinant human DNA is synthesized in bacteria
• Increlex® patent expires 2017

Publications

• Yang et al. “Reduced excitatory neurotransmission and mild autism-relevant phenotypes in adolescent Shank3 null mutant mice”. J. Neuroscience 2012 May 9;32(19):6525-41
• Bozdagi et al. “Insulin-like growth factor-1 rescues synaptic and motor deficits in a mouse model of autism and developmental delay”. Mol Autism. 2013 Apr 27;4(1):9

Patent Status

• International Application PCT/US2011/000860 filed May 16, 2011
• Status: Published. International Publication No. WO 2011/146109
• European Application EP11783855.7 filed May 16, 2011
• Status: Published. EP Publication No. EP2571515
• US Application 13/425,633 filed March 21, 2012
• Status: Issued. US Patent No. 8,691,762
• US Continuation Application 14/192,924 filed February 28, 2014
• Status: Pending

Contact

Jeanne Farrell, PhD
Business Development Director
Mount Sinai Innovation Partners | Icahn School of Medicine at Mount Sinai
Phone: 646.605.7314