The invention concerns a new therapeutic application of positive allosteric modulators of metabotropic glutamate receptor mGluR5, in particular for the therapeutic treatment of Phelan-McDermid syndrome caused by deletion 22q13.
The research team has decades of experience in the study of the pathogenesis of neurodevelopmental disorders such as intellectual disabilities and autism.
Among the most studied diseases Phelam-McDermid syndrome (PMS) is a genetic disease with no cure that causes a severe form of intellectual disability and autism. The lack of a copy of SHANK3 gene is the cause of neurological symptoms present in patients with the syndrome.
In recent years the group has developed cellular and animal models for the study of PMS including iPS cells from patients with the syndrome and knock out mice for SHANK3 protein. These experimental models are usable for the identification and development of drugs for the therapy of intellectual disability and autism.
The team demonstrated that the pharmacological increased activity of the mGluR5 receptor using the pharmacological compound CDPPB (3-Cyano-N- (1,3-diphenyl-1H-pyrazol-5-yl) benzamide), a positive allosteric modulator (PAM) of mGluR5, it’s possible to retrieve the synaptic dysfunction in neurons that do not express SHANK3 and to treat the cognitive impairments in the SHANK3 KO mice. The discovery open the possibility to use mGluR5 PAM drugs as a treatment for PMS and other form of intellectual disability and autism.