Oryzon Genomics, a clinical-phase biopharmaceutical company focused on epigenetics for the development of therapies for diseases with significant unmet medical needs, today announced the initiation of a preclinical collaboration on autism with researchers from the Seaver Center for Autism Research and Treatment at the Icahn School of Medicine at Mount Sinai Hospital led by Dr. Joseph Buxbaum.
Deletions or mutations at the end of chromosome 22 lead to a defect of the SHANK3 gene and produce in humans a variety of autism known as Phelan-McDermid syndrome (PMS). 80% of people with PMS have an autism spectrum disorder (ASD). In these patients, the inability of the remaining copy of the SHANK3 gene to produce enough Shank3 protein for normal neuronal function (haploinsufficiency) may be responsible for most of the neurological symptoms (developmental delay, autism, and lack of speech) associated with it. disorder. Recent work published by US researchers has shown that the LSD1-HDAC2 complex is involved in PMS and that, in Shank3-deficient animal models that recapitulate many symptoms of the human syndrome, inhibition of LSD1 restores neuronal electrophysiology and rescues deficits of learning. This collaboration will explore the effects of vafidemstat in animal models developed and characterized at the Seaver Center for Autism, a global reference center, by the team at Dr. Buxbaum, Center Director.
Vafidemstat is a selective, orally active LSD1 inhibitor that is in Phase II clinical development and has shown a very good safety profile and has been shown to be effective in reducing agitation and aggressiveness in clinical studies. in patients with Alzheimer’s disease, Borderline Personality Disorder (BPD), Attention deficit disorder and hyperactivity (ADHD) and ASD. Vafidemstat is currently being explored in a Phase IIb clinical trial in BPD (study PORTICO) and the company is also preparing a Phase IIb trial in schizophrenia (EVOLUTION study). The company is also exploring the use of vafidemstat in the field of precision psychiatry.
Professor Buxbaum, director of the Seaver Autism Center at the Icahn School of Medicine at Mount Sinai Hospital and lead investigator on the study, commented: “We have worked on Phelan-McDermid syndrome for over a decade and are really excited to see it. advance this potential treatment for this disorder. “
The doctor. Carlos Buesa, CEO of Oryzon, has said: “It is a great satisfaction to begin this collaboration with internationally renowned researchers such as those at the Seaver Autism Center at Mount Sinai. In recent years it has been proposed that epigenetic dysregulation in the histone H3K4 methylation pathway is a important mechanism in the pathogenesis of autism and other psychiatric and neurodevelopmental syndromes. Vafidemstat, with a good safety profile, could provide a therapeutic option for these patients in the future. “