Induced pluripotent stem cell (iPSC) technology to study Jansen de Vries Syndrome, Autism, and neuropsychiatric regression

Dr. Herbert Lachman, a physician-scientist at Albert Einstein College of Medicine and member of the Jansen de Vries Syndrome (JdVS) Foundation’s Medical Advisory Board, is pioneering research using induced pluripotent stem cells (iPSCs) to study JdVS. iPSCs have the unique ability to turn into any cell type in the body, including cells in the brain. Essentially, using iPSC technology allows investigators to grow "autism neurons" in the lab. We also use the gene editing tool called CRISPR to introduce autism mutations into iPSCs or correct an autism-associated mutation in the lab. JdVS is caused by mutations in the PPM1D gene, which disrupt DNA repair and mitochondrial function in neurons and microglia. The lab is testing drugs that block these mutations, with the goal of advancing to animal and clinical trials.

Beyond JdVS, Dr. Lachman’s lab has found that PPM1D mutations may also contribute to regressive autism and acute neuropsychiatric conditions like Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS), which are often triggered by infections. These are also poorly understood entities.  We are using iPSC-based research to study the effect of immune stimulation on neurons and microglia containing PANS-associated mutations.

Due to delays in NIH grant reviews, the lab is seeking to expand private donor funding. Thanks to the generosity of two donors, including the family of Ryan Stearn who provided the original funding for our JdVS iPSC project, the lab has been able to function along with some NIH funding. However, we are very concerned about a significant delay in future NIH grants. Subsequently, we are increasing our effort to expand our donor contributions.