The SHANK3 family of proteins plays a critical role in the functioning of synapses. Within synapses, the SHANK3 proteins act as scaffolds that connect neurons and influences dendrite spine maturation. Hence, the SHANK3 gene is essential to the development of the human nervous system. Phelan-McDermid Syndrome (PMS)—also called 22q13 Deletion Syndrome (22q13DS)—is a rare genetic syndrome in which one copy of the q13 portion of chromosome 22 is either missing or otherwise mutated. There is overwhelming evidence that it is the loss of one copy of the SHANK3 gene in this region is responsible for the neurological and behavioral aspects of the syndrome. Typically PMS/22q13DS is characterized by poor muscle tone, absent or delayed speech, intellectual disability, and can lead to behavioral symptoms that fall under the category of an autism spectrum disorder (ASD).
It has been shown that 0.5-1% of children with autism have deletions, duplications or mutations of the SHANK3 gene which translates to 10,000-20,000 individuals in the US will have a disability due to SHANK3 expression. Hence there is a need for a treatment for subjects with 22q13 deletion syndrome or SHANK3 mutations.
Researchers at the Icahn School of Medicine at Mount Sinai led by Professor Joseph Buxbaum developed a unique mouse model for SHANK3. Using this model, he was able to show that after two weeks of treatment with insulin-like growth factor-1 (IGF-1) deficits in nerve cell communication were reversed and deficiencies in adaptation of nerve cells to stimulation, a key part of learning and memory, were restored. As a result, a clinical trial was initiated and conducted under the guidance of Dr Alexander Kolevzon, the Clinical Director of the Seaver Autism Center at Mount Sinai who is also the sponsor of the trial.
The primary aim of the study is to target core features of ASD, including social withdrawal and language impairment, which will be measured using both behavioral and objective assessments. If preliminary results are promising, the goal is to expand the studies into larger, multi-centered efforts to include as many children as possible affected by this disorder. This is a pioneering study that test a drug that target the core symptom of autism.
Patent Status: Patent Pending