Rett syndrome study highlights potential for personalized treatments

MIT researchers at the Picower Institute used 3D human brain organoids to study two distinct MECP2 mutations causing Rett syndrome — R306C and V247X — and found they produce different structural, activity, and connectivity abnormalities. Using three-photon microscopy and single-cell RNA sequencing, the team identified mutation-specific molecular defects: HDAC2 overexpression in R306C and reduced GABA receptor expression in V247X. Crucially, each mutation responded to a different drug treatment — an HDAC2 inhibitor for R306C and the GABA agonist baclofen for V247X — demonstrating that even single-gene disorders may require personalized therapeutic approaches based on the specific mutation involved.