In Memoriam: Mavis Agbandje-McKenna (1963–2021)

On March 3, 2021, we lost an honored member of the virology community, Mavis Agbandje-McKenna, to amyotrophic lateral sclerosis (ALS). Mavis was a leading light in the fields of viral structure, functions, and gene therapy. She was also a treasured friend and collaborator to scientists around the world and an impactful mentor to a multitude of trainees.

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Gene Therapy for the Treatment of Neurological Disorders: Amyotrophic Lateral Sclerosis

Gene Therapy for Neurological Disorders - Methods in Molecular Biology ◽

10.1007/978-1-4939-3271-9_28 ◽

2016 ◽

pp. 399-408 ◽

Cited By ~ 2

Author(s):

Zachary T. McEachin ◽

Anthony Donsante ◽

Nicholas Boulis

Keyword(s):

Gene Therapy ◽

Amyotrophic Lateral Sclerosis ◽

Neurological Disorders ◽

Lateral Sclerosis

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Gene Therapy for Amyotrophic Lateral Sclerosis

Molecular and Cellular Therapies for Motor Neuron Diseases ◽

10.1016/b978-0-12-802257-3.00008-0 ◽

2017 ◽

pp. 167-205 ◽

Cited By ~ 1

Author(s):

A. Donsante

Keyword(s):

Gene Therapy ◽

Amyotrophic Lateral Sclerosis ◽

Lateral Sclerosis

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Beyond the Traditional Clinical Trials for Amyotrophic Lateral Sclerosis and The Future Impact of Gene Therapy

Journal of Neuromuscular Diseases ◽

10.3233/jnd-200531 ◽

2021 ◽

Vol 8 (1) ◽

pp. 25-38

Author(s):

Marisa Cappella ◽

Pierre-François Pradat ◽

Giorgia Querin ◽

Maria Grazia Biferi

Keyword(s):

Gene Therapy ◽

Clinical Trials ◽

Amyotrophic Lateral Sclerosis ◽

Muscular Atrophy ◽

Monogenic Disease ◽

Sporadic Als ◽

Pathological Mechanism ◽

Huge Impact ◽

Als Patients ◽

Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a devastating and incurable motor neuron (MN) disorder affecting both upper and lower MNs. Despite impressive advances in the understanding of the disease’s pathological mechanism, classical pharmacological clinical trials failed to provide an efficient cure for ALS over the past twenty years. Two different gene therapy approaches were recently approved for the monogenic disease Spinal muscular atrophy, characterized by degeneration of lower MNs. This milestone suggests that gene therapy-based therapeutic solutions could be effective for the treatment of ALS. This review summarizes the possible reasons for the failure of traditional clinical trials for ALS. It provides then a focus on the advent of gene therapy approaches for hereditary forms of ALS. Specifically, it describes clinical use of antisense oligonucleotides in three familial forms of ALS, caused by mutations in SOD1, C9orf72 and FUS genes, respectively.. Clinical and pre-clinical studies based on AAV-mediated gene therapy approaches for both familial and sporadic ALS cases are presented as well. Overall, this overview highlights the potential of gene therapy as a transforming technology that will have a huge impact on treatment perspective for ALS patients and on the design of future clinical trials.

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Prevalence of amyotrophic lateral sclerosis in the city of Porto Alegre, in Southern Brazil

Arquivos de Neuro-Psiquiatria ◽

10.1590/0004-282x20130177 ◽

2013 ◽

Vol 71 (12) ◽

pp. 959-962 ◽

Cited By ~ 9

Author(s):

Eduardo Linden Junior ◽

Jefferson Becker ◽

Pedro Schestatsky ◽

Francisco Tellechea Rotta ◽

Carlo Domenico Marrone ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Age Group ◽

Extensive Investigation ◽

Southern Brazil ◽

Porto Alegre ◽

Regional Association ◽

The World ◽

The City ◽

Lateral Sclerosis

Objective : To determine the prevalence of amyotrophic lateral sclerosis (ALS) in the city of Porto Alegre, Brazil. Method : We conducted an extensive investigation in clinics and hospitals that provide specialized assistance to these patients, contacted neurologists and the regional association of people with ALS. Results : On July 31, 2010, 70 patients were alive and diagnosed with amyotrophic lateral sclerosis. Considering the population living in the city in the same period (1,409,351), the estimated prevalence was 5.0 cases per 100,000 people (95% CI, 3.9-6.2), being higher for men (5.2/100,000 95% CI, 3.6-7.2) than for women (4.8/100,000 95% CI, 3.4-6.5). The prevalence increased with age peaking in the age group 70-79 years in both genders. Conclusion : The prevalence of ALS in the city of Porto Alegre is similar to that reported in other parts of the world.

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Amyotrophic lateral sclerosis: pathogenetic mechanisms and new approaches to pharmacotherapy (literature review)

Neuromuscular Diseases ◽

10.17650/2222-8721-2018-8-4-12-18 ◽

2019 ◽

Vol 8 (4) ◽

pp. 12-18

Author(s):

T. M. Alekseeva ◽

T. R. Stuchevskaya ◽

V. S. Demeshonok

Keyword(s):

Clinical Trials ◽

Amyotrophic Lateral Sclerosis ◽

New Drugs ◽

Significant Progress ◽

Future Directions ◽

Loss Of Self ◽

The World ◽

Self Service ◽

Lateral Sclerosis ◽

Made In

Amyotrophic lateral sclerosis is a neurodegenerative disease, resulting in the loss of self-service and death of the middle-aged and elderly people. In the last 2 decades, significant progress has been made in the study of the pathogenesis of this disease. Two known drugs (riluzole and edaravone) have been approved by the Food and Drug Administration for treatment of amyotrophic lateral sclerosis. The efficacy of these drugs is extremely low, so clinical trials of new drugs are ongoing all over the world. This review discusses the current achievements and future directions of therapy of this disease.

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Impact of a frequent nearsplice SOD1 variant in amyotrophic lateral sclerosis: optimising SOD1 genetic screening for gene therapy opportunities

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2020-325921 ◽

2021 ◽

pp. jnnp-2020-325921

Author(s):

François Muratet ◽

Elisa Teyssou ◽

Aude Chiot ◽

Séverine Boillée ◽

Christian S Lobsiger ◽

...

Keyword(s):

Gene Therapy ◽

Amyotrophic Lateral Sclerosis ◽

Superoxide Dismutase ◽

Motor Neuron ◽

Systematic Analysis ◽

Large Pedigree ◽

Copper Zinc Superoxide Dismutase ◽

Unknown Significance ◽

Mutation Distribution ◽

Lateral Sclerosis

ObjectiveMutations in superoxide dismutase 1 gene (SOD1), encoding copper/zinc superoxide dismutase protein, are the second most frequent high penetrant genetic cause for amyotrophic lateral sclerosis (ALS) motor neuron disease in populations of European descent. More than 200 missense variants are reported along the SOD1 protein. To limit the production of these aberrant and deleterious SOD1 species, antisense oligonucleotide approaches have recently emerged and showed promising effects in clinical trials. To offer the possibility to any patient with SOD1-ALS to benefit of such a gene therapy, it is necessary to ascertain whether any variant of unknown significance (VUS), detected for example in SOD1 non-coding sequences, is pathogenic.MethodsWe analysed SOD1 mutation distribution after SOD1 sequencing in a large cohort of 470 French familial ALS (fALS) index cases.ResultsWe identified a total of 27 SOD1 variants in 38 families including two SOD1 variants located in nearsplice or intronic regions of the gene. The pathogenicity of the c.358–10T>G nearsplice SOD1 variant was corroborated based on its high frequency (as the second most frequent SOD1 variant) in French fALS, the segregation analysis confirmed in eight affected members of a large pedigree, the typical SOD1-related phenotype observed (with lower limb onset and prominent lower motor neuron involvement), and findings on postmortem tissues showing SOD1 misaccumulation.ConclusionsOur results highlighted nearsplice/intronic mutations in SOD1 are responsible for a significant portion of French fALS and suggested the systematic analysis of the SOD1 mRNA sequence could become the method of choice for SOD1 screening, not to miss these specific cases.

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