Recent progress of the genetics of amyotrophic lateral sclerosis and challenges of gene therapy

Hui Wang; LiPing Guan; Min Deng

doi:10.3389/fnins.2023.1170996

Recent progress of the genetics of amyotrophic lateral sclerosis and challenges of gene therapy

Front Neurosci. 2023 May 12:17:1170996. doi: 10.3389/fnins.2023.1170996. eCollection 2023.

Authors

Hui Wang¹, LiPing Guan^{1

2}, Min Deng^{1

2}

Affiliations

¹ Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing, China.
² Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark.

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the degeneration of motor neurons in the brain and spinal cord. The causes of ALS are not fully understood. About 10% of ALS cases were associated with genetic factors. Since the discovery of the first familial ALS pathogenic gene SOD1 in 1993 and with the technology advancement, now over 40 ALS genes have been found. Recent studies have identified ALS related genes including ANXA11, ARPP21, CAV1, C21ORF2, CCNF, DNAJC7, GLT8D1, KIF5A, NEK1, SPTLC1, TIA1, and WDR7. These genetic discoveries contribute to a better understanding of ALS and show the potential to aid the development of better ALS treatments. Besides, several genes appear to be associated with other neurological disorders, such as CCNF and ANXA11 linked to FTD. With the deepening understanding of the classic ALS genes, rapid progress has been made in gene therapies. In this review, we summarize the latest progress on classical ALS genes and clinical trials for these gene therapies, as well as recent findings on newly discovered ALS genes.

Keywords: amyotrophic lateral sclerosis; antisense oligonucleotide; gene therapy; genetics; motoneuron disease; neurogenetics.

Publication types

Review