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Review
. 2022 Sep 15;13(9):1655.
doi: 10.3390/genes13091655.

SLC13A5 Deficiency Disorder: From Genetics to Gene Therapy

Kimberly Goodspeed  1 , Judy S Liu  2 , Kimberly L Nye  3 , Suyash Prasad  4 , Chanchal Sadhu  4 , Fatemeh Tavakkoli  4 , Deborah A Bilder  5 , Berge A Minassian  1 , Rachel M Bailey  1   6
Affiliations
Review

SLC13A5 Deficiency Disorder: From Genetics to Gene Therapy

Kimberly Goodspeed et al. Genes (Basel). .

Abstract

Epileptic encephalopathies may arise from single gene variants. In recent years, next-generation sequencing technologies have enabled an explosion of gene identification in monogenic epilepsies. One such example is the epileptic encephalopathy SLC13A5 deficiency disorder, which is caused by loss of function pathogenic variants to the gene SLC13A5 that results in deficiency of the sodium/citrate cotransporter. Patients typically experience seizure onset within the first week of life and have developmental delay and intellectual disability. Current antiseizure medications may reduce seizure frequency, yet more targeted treatments are needed to address the epileptic and non-epileptic features of SLC13A5 deficiency disorder. Gene therapy may offer hope to these patients and better clinical outcomes than current available treatments. Here, we discuss SLC13A5 genetics, natural history, available treatments, potential outcomes and assessments, and considerations for translational medical research for an AAV9-based gene replacement therapy.

Keywords: AAV9; SLC13A5; epileptic encephalopathy; gene therapy; sodium/citrate cotransporter.

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Conflict of interest statement

K.G. receives salary and research support from Taysha Gene Therapies; received research support from Neurogene, Inc.; and has provided consultation to Jaguar Gene Therapies. S.P. and C.S. are current employees, and F.T. is a former employee of Taysha Gene Therapies. D.A.B. is a member of the Scientific Advisory Board for Taysha Gene Therapies and a consultant for Encoded Therapeutics, BioMarin Pharmaceuticals, and Synlogic Therapeutics. B.A.M. holds the University of Texas Southwestern Jimmy Elizabeth Westcott Chair in Pediatric Neurology, is Chief Medical Advisor at Taysha Gene Therapies, and receives salary and research support from Taysha Gene Therapies. R.M.B. has sponsored research agreements with Taysha Gene Therapies and is an inventor on patents that have been licensed to various biopharmaceutical companies and for which she may receive payments.

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Supplementary concepts