Gene-Targeted Therapies in Pediatric Neurology: Challenges and Opportunities in Diagnosis and Delivery

Renée A Shellhaas; Gabrielle deVeber; Joshua L Bonkowsky; Child Neurology Society Research Committee

doi:10.1016/j.pediatrneurol.2021.09.011

Gene-Targeted Therapies in Pediatric Neurology: Challenges and Opportunities in Diagnosis and Delivery

Pediatr Neurol. 2021 Dec:125:53-57. doi: 10.1016/j.pediatrneurol.2021.09.011. Epub 2021 Sep 25.

Authors

Renée A Shellhaas¹, Gabrielle deVeber², Joshua L Bonkowsky³; Child Neurology Society Research Committee

Collaborators

Child Neurology Society Research Committee:
Erika F Augustine⁴, Alexander G Bassuk⁵, Daniel G Calame⁶, Melisa Carrasco⁷, Nomazulu Dlamini⁸, Ryan J Felling⁹, Hannah C Glass¹⁰, Zachary M Grinspan¹¹, Réjean M Guerriero¹², Angela Hewitt¹³, Shafali Jeste¹⁴, Juliet K Knowles¹⁵, Ariel M Lyons-Warren¹⁶, Stephen M Maricich¹⁷, Patricia L Musolino¹⁸, G Praveen Raju¹⁹, Jong M Rho²⁰, Alexander Rotenberg²¹, Elliott Sherr²², Janet S Soul²³, Julie Ziobro²⁴

Affiliations

¹ Department of Pediatrics, University of Michigan (Michigan Medicine), Ann Arbor, Michigan. Electronic address: [email protected].
² Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada.
³ Department of Pediatrics, University of Utah School of Medicine, Primary Children's Hospital, Intermountain Healthcare, Salt Lake City, Utah.
⁴ Department of Neurodevelopmental Medicine, Kennedy Krieger Institute, Baltimore, Maryland.
⁵ Department of Pediatrics, University of Iowa, Iowa City, Iowa.
⁶ Section of Pediatric Neurology and Developmental Neuroscience, Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
⁷ Department of Neurology, University of Wisconsin, Madison, Wisconsin.
⁸ Department of Paediatrics and Division of Neurology, Hospital for Sick Children, Toronto, Ontario, Canada.
⁹ Departments of Neurology and Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland.
¹⁰ Department of Neurology and Weill Institute for Neuroscience, University of California San Francisco, San Francisco, California; Department of Pediatrics, UCSF Benioff Children's Hospital, University of California San Francisco, San Francisco, California; Department of Epidemiology & Biostatistics, University of California San Francisco, San Francisco, California.
¹¹ Departments of Population Health Sciences and Pediatrics, Weill Cornell Medicine, New York, New York.
¹² Division of Pediatric and Developmental Neurology, Department of Neurology, Washington University School of Medicine, St. Louis, Missouri.
¹³ Department of Neurology, University of Rochester, Rochester, New York.
¹⁴ Departments of Psychiatry, Neurology and Pediatrics at the UCLA David Geffen School of Medicine, Los Angeles, California.
¹⁵ Assistant Professor, Child Neurology and Epilepsy, Stanford University School of Medicine, Stanford, California.
¹⁶ Instructor, Division of Child Neurology, Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas.
¹⁷ Chief Medical Officer, Allievex Corporation, Marblehead, Massachusetts.
¹⁸ Department of Neurology and Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
¹⁹ Departments of Neurology and Pediatrics, Kravis Children's Hospital, Icahn School of Medicine at Mount Sinai, New York, New York.
²⁰ Rady Children's Hospital, San Diego, La Jolla, California.
²¹ Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.
²² Departments of Neurology and Pediatrtics, Institute of Human Genetics, Weill Institute for Neuroscience, University of California San Francisco, San Francisco, California.
²³ Associate Professor, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.
²⁴ Department of Pediatrics (Pediatric Neurology), Michigan Medicine, University of Michigan, Ann Arbor, Michigan.

PMID: 34628144
PMCID: PMC9472447
DOI: 10.1016/j.pediatrneurol.2021.09.011

Abstract

Background: Gene-targeted therapies are becoming a reality for infants and children with diseases of the nervous system. Rapid scientific advances have led to disease-modifying or even curative treatments. However, delays and gaps in diagnosis, inequitable delivery, and the need for long-term surveillance pose unresolved challenges.

Objective and methods: The goal of the Child Neurology Society Research Committee was to evaluate and provide guidance on the obstacles, opportunities, and uncertainties in gene-targeted therapies for pediatric neurological disease. The Child Neurology Society Research Committee engaged in collaborative, iterative literature review and committee deliberations to prepare this consensus statement.

Results: We identified important challenges for gene-targeted therapies that require resource investments, infrastructure development, and strategic planning. Barriers include inequities in diagnosis and delivery of therapies, high costs, and a need for long-term surveillance of efficacy and safety, including systematic tracking of unanticipated effects. Key uncertainties regarding technical aspects and usage of gene-targeted therapies should be addressed, and characterization of new natural histories of diseases will be needed. Counterbalanced with these obstacles and uncertainties is the tremendous potential being demonstrated in treatments and clinical trials of gene-targeted therapies.

Conclusions: Given that gene-targeted therapies for neurological diseases are in their earliest phase, the pediatric neurology community can play a vital role in their guidance and implementation. This role includes facilitating development of infrastructure and guidelines; ensuring efficient, equitable, and ethical implementation of treatments; and advocating for affordable and broad access for all children.

Keywords: Antisense oligonucleotide; Child neurology; Diagnosis; Disparities; Ethics; Gene therapy; Health economics; Rare disease.

MeSH terms

Child
Gene Targeting* / standards
Genetic Therapy* / standards
Humans
Nervous System Diseases / therapy*
Neurology* / methods
Neurology* / organization & administration
Neurology* / standards
Pediatrics* / methods
Pediatrics* / organization & administration
Pediatrics* / standards

Abstract

MeSH terms

Grants and funding