Page 12 - Rappaport Institute Magazine 2024

BIOCHEMISTRY
Andrew P Levy MD, PHD Professor of Functional Genomics
MD PhD, 1990 – Johns Hopkins University, USA
Precision medicine for the treatment of IQSEC2 disease
My research over the past 25 years at the Technion has focused on functional genomics and personalized medicine. Over the past few years for reasons close to home we have moved the focus of our laboratory on finding a treatment for a devastating disease in children associated with drug resistant epilepsy, autism and severe intellectual disability caused by a mutation in the IQSEC2 gene. We have currently studying the disease in zebrafish, mouse and human stem cell platforms and are using these platforms to investigate new therapies to treat the disease. We have recently generated a novel gene therapy approach that can prevent seizures in mice with IQSEC2 mutations. We hope to move to proof of concept clinical trials in children in the near future using this gene therapy approach.
Selected Publications
ˆ Brant B, Tchelet Stern T, Shekhidem H, Mizrahi L, Rosh I, Stern Y, Ofer P, Asleh A, Umanah G, Jada R, Levy NS, Levy AP*, Shani Stern S*(* co-corresponding authors). IQSEC2 Mutation Associated with Epilepsy, Intellectual Disability and Autism Results in Hyperexcitability of Patient Derived Neurons and Deficient Synaptic transmission. Mol Psychiatry 2021; doi.org/10.1038/s41380-021-01281-0
ˆ Shokhen M, Walikonis R, Uversky VN, Allbeck A, Zezelic C, Feldman D, Levy NS, Levy AP. Molecular modeling of ARF6 dysregulation caused by mutations in IQSEC2. J Biomol Structure 2023; 20:1-12; doi 10.1080/07391102.2023.2199085.
ˆ Levy NS, Borisov V, Lache O, Levy AP. Molecular Insights into IQSEC2 disease.
Int J Mol Sci 2023; 5: 4984; doi: 10.3390/ijms24054984
Collaborators
USA: Randall Walonkonis (U Conn), Tristan Sands (Columbia Univ), Eric Marsh (CHOP), Scott Harper (Nationwide Childrens Hospital)
alevy@technion.ac.il
Andrew Levy Lab
Confocal image of dendritic processes of neurons derived from mice with an IQSEC2 mutation. The IQSEC2 protein regulates
the growth and maturation of dendritic spines, which are the sites where neurons communicate with one another.