Disruption of X-linked methyl CpG-binding protein 2 (MECP2) causes Rett syndrome (RTT) - a devastating neurodevelopmental disorder leading to nonsyndromic mental retardation, learning disability, and autism. Currently there is no cure. We recently identified a molecular defect that is a likely cause of RTT – the mis-regulation of long highly methylated genes through MECP2 dysfunction. Notably, many of the mis-regulated highly methylated long genes are required for proper neuronal functions including synapses that underlie learning and memory. We hypothesize that restoring the expression of mis-regulated long genes and synaptic development may be key to treating RTT. A score of hits were identified and the majority were successfully validated by a series of in vitro experiments. Moreover, structural, pharmacokinetic (PK) and blood-brain-barrier (BBB) permeability analyses suggest favorable chemistry for therapeutics. In the next phase of study, we plan to further the drug development by focusing on behavioral testing while starting to investigate potential drug targets and mechanism of action (MOA).

Funding

Funding Duration

July 1, 2016 - June 30, 2017

Funding level

Pilot

People

Principal Investigator

Michael Greenberg

PhD
Nathan Marsh Pusey Professor of Neurobiology, Harvard Medical School
Co-PI

Follow on Funding and Exits

Federal/Foundations Funding