Neurodevelopmental Disorders

Epilepsy and Neuro-developmental disorders (NDD) are often caused by genetic mutations that lead to haploinsufficiency, or a loss-of-gene function. Mutations that cause haploinsufficiency of neurodevelopmental genes affect over 200,000 births each year, and commonly result in congenital malformations, intellectual disability, epilepsy and motor and behavioral impairments. While symptomatic treatments exist, for most conditions there are no treatments that directly correct the reduced levels of the haploinsufficient gene. 

To tackle this issue, we’re thrilled to announce the formation of the ENDD Therapeutics Team, a multi-disciplinary group of investigators focused on developing new therapies for these intractable conditions. The core labs include the Prosser and Heller Labs at Penn and the Davidson Lab at CHOP. We also work closely with Debbie French and the Human Pluripotent Stem Cell Core at CHOP to develop iPS-models of NDD and test novel therapies, and with Dr. Ingo Helbig, a neurogeneticist at CHOP, as our clinical consultant.  

The group is focused on developing anti-sense oligonucleotide (ASO), small molecule, and CRISPR-based strategies for the treatment of NDD, with our initial focus on STXBP1- and SYNGAP1-related disorders. The ENDD team is supported by collaborations with the pharmaceutical and biotechnology sector, private foundations including the Syngap Research Fund and STXBP1 Foundation, and philanthropic efforts.

Related Publications

Assessing the landscape of STXBP1-related disorders in 534 individuals

Assessing the landscape of STXBP1-related disorders in 534 individuals.

Xian J, Parthasarathy S, Ruggiero SM, Balagura G, Fitch E, Helbig K, Gan J, Ganesan S, Kaufman MC, Ellis CA, Lewis-Smith D, Galer P, Cunningham K, O’Brien M, Cosico M, Baker K, Darling A, Veiga de Goes F, El Achkar CM, Doering JH, Furia F, García-Cazorla Á, Gardella E, Geertjens L, Klein C, Kolesnik-Taylor A, Lammertse H, Lee J, Mackie A, Misra-Isrie M, Olson H, Sexton E, Sheidley B, Smith L, Sotero L, Stamberger H, Syrbe S, Thalwitzer KM, van Berkel A, van Haelst M, Yuskaitis C, Weckhuysen S, Prosser B, Son Rigby C, Demarest S, Pierce S, Zhang Y, Møller RS, Bruining H, Poduri A, Zara F, Verhage M, Striano P, Helbig I.

Brain. 2022 Jun 3;145(5):1668-1683. doi: 10.1093/brain/awab327. PMID: 35190816
Neurodevelopmental Disorders

Base editing the synapse: Modeling a complex neurological disorder in non-human primates.

Base editing the synapse: Modeling a complex neurological disorder in non-human primates.
Prosser BL, Helbig I.

Mol Ther. 2022 Jun 1;30(6):2114-2116. doi: 10.1016/j.ymthe.2022.05.009. Epub 2022 May 24. PMID: 35613622
Neurodevelopmental Disorders