Phelan-McDermid Syndrome, page-97

Apologies if this has been covered before, but looking into the PMD trial, I was thinking that this is no accident that it is the first off the rank in the Ph2 trials. My understanding is that 2591 is believed to the efficacious with the production of the SHANK3 gene. Now, I'm not sure if the 2591 molecule replaces the function of the SHANK3 (in that it creates the protein that assists in synaptic function) or whether 2591 provides the stimulus for the gene to switch on.

Either way, success in the SHANK3, opens up the discussion on the wider Autism spectrum as at least 43 SHANK3 mutations have been found in people with ASD.

This from Huang et al.
Although Shank3 mutation is heterozygous in humans, the analysis and identification of Shank3 homozygous mutant mice are imperative for understanding the physiological role of Shank3 and its functional consequences. In addition, the mutation has destructive effects. In terms of the treatment window, the earlier the treatment is administered, the better the outcome. However, interventions in adulthood may still be useful for reducing some of the symptoms associated with SHANK3 mutations. It is necessary to carefully analyze the specific phenotype of a genotype before trying a drug alone. Exploring the SHANK3 gene may help uncover some of the neurobiological aspects of autism.