New and developing therapies in spinal muscular atrophy

Didu Kariyawasam; Kate A Carey; Kristi J Jones; Michelle A Farrar

doi:10.1016/j.prrv.2018.03.003

New and developing therapies in spinal muscular atrophy

Paediatr Respir Rev. 2018 Sep:28:3-10. doi: 10.1016/j.prrv.2018.03.003. Epub 2018 Apr 5.

Authors

Didu Kariyawasam¹, Kate A Carey², Kristi J Jones³, Michelle A Farrar⁴

Affiliations

¹ Department of Neurology, Sydney Children's Hospitals Network, Sydney, Australia.
² Department of Neurology, Sydney Children's Hospitals Network, Sydney, Australia; Discipline of Paediatrics, School of Women's and Children's Health, UNSW Medicine, The University of New South Wales, Sydney, Australia.
³ Disciplines Genetics and Paediatrics and Child Health, The Children's Hospital at Westmead Clinical School, The University of Sydney, Sydney, Australia.
⁴ Department of Neurology, Sydney Children's Hospitals Network, Sydney, Australia; Discipline of Paediatrics, School of Women's and Children's Health, UNSW Medicine, The University of New South Wales, Sydney, Australia. Electronic address: m.farrar@unsw.edu.au.

PMID: 29703692
DOI: 10.1016/j.prrv.2018.03.003

Abstract

Great progress has been made in the clinical translation of several therapeutic strategies for spinal muscular atrophy (SMA), including measures to selectively address Survival Motor Neuron (SMN) protein deficiency with SMN1 gene replacement or modulation of SMN2 encoded protein levels, as well as neuroprotective approaches and supporting muscle strength and function. This review highlights these novel therapies. This is particularly vital with the advent of the first disease modifying therapy, which has brought to the fore an array of questions surrounding who, how and when to treat, and stimulated challenges in resource limited healthcare systems to streamline access for those eligible for drug therapy. The overhaul of the landscape for all those involved in SMA extends to the design of further drug trials and the necessity of multidisciplinary supportive care to potentiate the effects of disease modifying medications. The impact of respiratory complications in SMA is central to management in the current era of emerging novel therapies. These fundamental changes in our knowledge and management approach to those with SMA are explored further in this review.

Keywords: Gene therapy; Nusinersen; Spinal muscular atrophy; Survival motor neuron; Treatment.

Publication types

Review

MeSH terms

Cholestenones / therapeutic use*
Genetic Therapy / methods*
Humans
Imidazoles / therapeutic use*
Neuroprotective Agents / therapeutic use*
Oligonucleotides / therapeutic use*
Physical Therapy Modalities*
Pyrazines / therapeutic use*
Respiration, Artificial
Spinal Muscular Atrophies of Childhood / genetics
Spinal Muscular Atrophies of Childhood / therapy*
Survival of Motor Neuron 1 Protein / genetics
Survival of Motor Neuron 2 Protein / genetics

Substances

CK-2017357
Cholestenones
Imidazoles
Neuroprotective Agents
Oligonucleotides
Pyrazines
SMN1 protein, human
SMN2 protein, human
Survival of Motor Neuron 1 Protein
Survival of Motor Neuron 2 Protein
nusinersen
olesoxime