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Novel genome-editing-based approaches to treat motor neuron diseases: Promises and challenges.
Miccio, Annarita; Antoniou, Panagiotis; Ciura, Sorana; Kabashi, Edor.
Afiliação
  • Miccio A; Laboratory of Chromatin and Gene Regulation during Development, Imagine Institute, Université de Paris, INSERM UMR 1163, 75015, Paris, France. Electronic address: annarita.miccio@institutimagine.org.
  • Antoniou P; Laboratory of Chromatin and Gene Regulation during Development, Imagine Institute, Université de Paris, INSERM UMR 1163, 75015, Paris, France.
  • Ciura S; Laboratory of Translational Research for Neurological Disorders, Imagine Institute, Université de Paris, INSERM UMR 1163, 75015, Paris, France.
  • Kabashi E; Laboratory of Translational Research for Neurological Disorders, Imagine Institute, Université de Paris, INSERM UMR 1163, 75015, Paris, France. Electronic address: edor.kabashi@institutimagine.org.
Mol Ther ; 30(1): 47-53, 2022 01 05.
Article em En | MEDLINE | ID: mdl-33823304
Motor neuron diseases are untreatable with common pharmacological approaches. Spinal muscular atrophy (SMA) is caused by SMN1 gene mutations leading to lowered SMN expression. Symptoms are alleviated in infants with a higher copy number of the SMN2 gene, which, however, displays a splicing defect resulting in low SMN levels. Amyotrophic lateral sclerosis (ALS) is caused by a number of mutations, with C9orf72 repeat expansions the most common genetic cause and SOD1 gain-of-function mutations the first genetic cause identified for this disease. Genetic therapies based on oligonucleotides that enhance SMN2 splicing and SMN production or lower SOD1 expression have shown promise in initial clinical trials for individuals with SMA and ALS harboring SOD1 mutations, respectively. Gene addition/silencing approaches using adeno-associated viruses (AAVs) are also currently under clinical investigation in trials for SMA and ALS. Here we provide a brief overview of these efforts and their advantages and challenges. We also review genome editing approaches aimed at correcting the disease-causing mutations or modulating the expression of genetic modifiers, e.g., by repairing SOD1 mutations or the SMN2 splicing defect or deleting C9orf72 expanded repeats. These studies have shown promising results to approach therapeutic trials that should significantly lower the progression of these deadly disorders.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Atrofia Muscular Espinal / Esclerose Lateral Amiotrófica Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Atrofia Muscular Espinal / Esclerose Lateral Amiotrófica Idioma: En Ano de publicação: 2022 Tipo de documento: Article