Gene-based therapeutics for rare genetic neurodevelopmental psychiatric disorders

Beverly L Davidson; Guangping Gao; Elizabeth Berry-Kravis; Allison M Bradbury; Carsten Bönnemann; Joseph D Buxbaum; Gavin R Corcoran; Steven J Gray; Heather Gray-Edwards; Robin J Kleiman; Adam J Shaywitz; Dan Wang; Huda Y Zoghbi; Terence R Flotte; Sitra Tauscher-Wisniewski; Cynthia J Tifft; Mustafa Sahin; Gene Therapy Workshop Faculty

doi:10.1016/j.ymthe.2022.05.014

Gene-based therapeutics for rare genetic neurodevelopmental psychiatric disorders

Mol Ther. 2022 Jul 6;30(7):2416-2428. doi: 10.1016/j.ymthe.2022.05.014. Epub 2022 May 17.

Authors

Beverly L Davidson¹, Guangping Gao², Elizabeth Berry-Kravis³, Allison M Bradbury⁴, Carsten Bönnemann⁵, Joseph D Buxbaum⁶, Gavin R Corcoran⁷, Steven J Gray⁸, Heather Gray-Edwards⁹, Robin J Kleiman¹⁰, Adam J Shaywitz¹¹, Dan Wang¹², Huda Y Zoghbi¹³, Terence R Flotte¹⁴, Sitra Tauscher-Wisniewski¹⁵, Cynthia J Tifft¹⁶, Mustafa Sahin¹⁷; Gene Therapy Workshop Faculty

Affiliations

¹ Raymond G. Perelman Center for Cellular and Molecular Therapeutics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: davidsonbl@chop.edu.
² Horae Gene Therapy Center, UMass Chan Medical School, Worcester, MA, USA; Li Weibo Institute for Rare Diseases Research, UMass Chan Medical School, Worcester, MA, USA; Department of Microbiology and Physiological Systems, UMass Chan Medical School, Worcester, MA, USA. Electronic address: guangping.gao@umassmed.edu.
³ Departments of Pediatrics, Neurological Sciences, Anatomy and Cell Biology, Rush University Medical Center, Chicago, IL, USA.
⁴ Department of Pediatrics, Abigail Wexner Research Institute Nationwide Children's Hospital, The Ohio State University, Columbus, OH, USA.
⁵ National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
⁶ Seaver Autism Center for Research and Treatment, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁷ TrialSpark, New York, NY, USA.
⁸ Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
⁹ Horae Gene Therapy Center, UMass Chan Medical School, Worcester, MA, USA; Department of Radiology, UMass Chan Medical School, Worcester, MA, USA.
¹⁰ Biogen Research and Development, Cambridge, MA, USA.
¹¹ BridgeBio Gene Therapy, Palo Alto, CA, USA.
¹² Horae Gene Therapy Center, UMass Chan Medical School, Worcester, MA, USA; RNA Therapeutics Institute, UMass Chan Medical School, Worcester, MA, USA.
¹³ Howard Hughes Medical Institute, Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.
¹⁴ Horae Gene Therapy Center, UMass Chan Medical School, Worcester, MA, USA.
¹⁵ Novartis Gene Therapies, Bannockburn, IL, USA.
¹⁶ Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
¹⁷ Rosamund Stone Zander Translational Neuroscience Center, Department of Neurology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA. Electronic address: mustafa.sahin@childrens.harvard.edu.

Abstract

We are in an emerging era of gene-based therapeutics with significant promise for rare genetic disorders. The potential is particularly significant for genetic central nervous system disorders that have begun to achieve Food and Drug Administration approval for select patient populations. This review summarizes the discussions and presentations of the National Institute of Mental Health-sponsored workshop "Gene-Based Therapeutics for Rare Genetic Neurodevelopmental Psychiatric Disorders," which was held in January 2021. Here, we distill the points raised regarding various precision medicine approaches related to neurodevelopmental and psychiatric disorders that may be amenable to gene-based therapies.

Keywords: gene therapy; neurodevelopment; psychiatric disorders.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Humans
Mental Disorders* / genetics
Mental Disorders* / psychology
Mental Disorders* / therapy
Precision Medicine*
Rare Diseases
United States
United States Food and Drug Administration

Abstract

Publication types

MeSH terms

Grants and funding