Current developments in gene therapy for amyotrophic lateral sclerosis

Abstract

Introduction: Amyotrophic lateral sclerosis (ALS) is a devastating adult neurodegenerative disorder characterized by motor neuron degeneration and death around 3 years from onset. So far, riluzole is the only treatment available, although it only offers a slight increase in survival. The complex etiology of ALS, with several genes able to trigger the disease, makes its study difficult.

Areas covered: RNA-mediated or protein-mediated toxic gain-of-function leading to motor neuron degeneration appears to be likely common pathogenic mechanisms in ALS. Consequently, gene therapy technologies to reduce toxic RNA and/or proteins and to protect motor neurons by modulating gene expression are at the forefront of the field. Here, we review the most promising scientific advances, paying special attention to the successful treatments tested in animal models as well as analyzing relevant gene therapy clinical trials.

Expert opinion: Despite broad advances in target gene identification in ALS and advances in gene therapy technologies, a successful gene therapy for ALS continues to elude researchers. Multiple hurdles encompassing technical, biological, economical and clinical challenges must be overcome before a therapy for patients becomes available. Optimism remains due to positive results obtained in several in vivo studies demonstrating significant disease amelioration in animal models of ALS.

Keywords:

• adeno-associated virus
• amyotrophic lateral sclerosis
• gene therapy
• self-complementary adeno-associated virus serotype 9

Acknowledgment

JM Scarrott and S Herranz-Martín are contributed equally to the work.

Declaration of interest

M Azzouz and S Herranz-Martín are supported by an ERC Advanced Investigator Award. JM Scarrott is supported by University of Sheffield studentship. AR Alrafiah is supported by scholarship from King Abdulaziz University. PJ Shaw is supported as an NIHR Senior Investigator. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

Notes

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