Renée A Shellhaas1, Gabrielle deVeber2, Joshua L Bonkowsky3. 1. Department of Pediatrics, University of Michigan (Michigan Medicine), Ann Arbor, Michigan. Electronic address: shellhaa@med.umich.edu. 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.
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.
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.
Authors: Emilia M Gatto; Ruth H Walker; Claudio Gonzalez; Martin Cesarini; Giovanni Cossu; Christopher D Stephen; Bettina Balint; Mayela Rodríguez-Violante; Joseph Jankovic; Francesca Morgante; Hyder A Jinnah Journal: Eur J Neurol Date: 2021-03-17 Impact factor: 6.089
Authors: William A Gahl; John J Mulvihill; Camilo Toro; Thomas C Markello; Anastasia L Wise; Rachel B Ramoni; David R Adams; Cynthia J Tifft Journal: Mol Genet Metab Date: 2016-01-22 Impact factor: 4.797
Authors: Meaghan Van Alstyne; Ivan Tattoli; Nicolas Delestrée; Yocelyn Recinos; Eileen Workman; Lamya S Shihabuddin; Chaolin Zhang; George Z Mentis; Livio Pellizzoni Journal: Nat Neurosci Date: 2021-04-01 Impact factor: 24.884
Authors: Erik Landfeldt; Peter Lindgren; Christopher F Bell; Claude Schmitt; Michela Guglieri; Volker Straub; Hanns Lochmüller; Katharine Bushby Journal: Neurology Date: 2014-07-02 Impact factor: 9.910
Authors: Juliet K Knowles; Ingo Helbig; Cameron S Metcalf; Laura S Lubbers; Lori L Isom; Scott Demarest; Ethan M Goldberg; Alfred L George; Holger Lerche; Sarah Weckhuysen; Vicky Whittemore; Samuel F Berkovic; Daniel H Lowenstein Journal: Epilepsia Date: 2022-07-17 Impact factor: 6.740