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Revealing in the primary cilium a novel therapeutic target for the treatment of Rett syndrome

MECP2 mutations


Mutations in the MECP2 gene are responsible for a large spectrum of neurological disorders mostly affecting females. Among these, Rett syndrome represents the best defined and frequent condition. No cure is currently available for MECP2 disorders, and ongoing treatments are usually based on supportive therapies. The attainment of efficient therapies requires a better understanding of the functions exerted by MeCP2 beyond its well‐known role as a transcriptional regulator.


We demonstrate that MeCP2 is involved in the correct formation and functioning of primary cilium, a cellular organelle that emerges from the surface of every mammalian cells and is altered in a set of diseases defined “ciliopathies” that share some clinical traits with Rett syndrome. These defects have been observed in cultured cells defective for MeCP2, in the brain of transgenic mice modeling the disease and in Rett patients’ fibroblasts. We have rationally designed pharmacological interventions that are able to rescue the structure and function of primary cilia in MeCP2‐defective cells. Importantly, these drugs have the capacity to recover neuronal defects typical of Rett syndrome.


By demonstrating the involvement of MeCP2 in ciliogenesis, we highlight a novel therapeutic target for MECP2 disorders. Although we do not want to define Rett syndrome as a ciliopathy, we highlight the importance to considering whether novel pharmacological approaches effective for ciliopathies could be re‐directed for Rett syndrome.



MECP2 mutations affect ciliogenesis: a novel perspective for Rett syndrome and related disorders

EMBO Mol Med (2020) e10270 [Epub ahead of print]




Prof. Nicoletta Landsberger

Dr.ssa Angelisa Frasca

Dip. di Biotecnologie Mediche e Medicina Traslazionale
Università degli Studi di Milano
Via F.lli Cervi, 93
20090 Segrate (MI)



11 May 2020
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