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Alzheimer's Disease (AD), a neurodegenerative disorder, is pathologically identified by amyloid plaques and neurofibrillary tangles composed of tau protein. AD pharmacotherapy aims to manage cognitive symptoms, delay disease progression, and treat behavioral symptoms. The treatment is primarily symptomatic and palliative, with no definitive disease-modifying therapy available. Cholinesterase inhibitors, including donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne), are...
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Updated: Aug 17, 2025

ALS - Motor Neuron Disease: Mechanism and Development of New Therapies
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Therapeutic tools for familial ALS.

W Camu1, E De La Cruz1, F Esselin1

  • 1Explorations neurologiques et centre de référence SLA, université de Montpellier, CHU Gui de Chauliac, INM, Inserm, Montpellier, France.

Revue Neurologique
|December 12, 2022
PubMed
Summary

Gene-specific therapies show promise for familial ALS (FALS), with antisense oligonucleotides (ASO) and viral vectors targeting SOD1 mutations. Microbiota modulation offers a safe alternative for C9ORF72 models, indicating evolving FALS treatment strategies.

Keywords:
AAVC9OR72Familial ALSGene therapySOD1

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Area of Science:

  • Neuroscience
  • Genetics
  • Pharmacology

Background:

  • Familial Amyotrophic Lateral Sclerosis (FALS) constitutes 10-15% of ALS cases, with identified causal genes in over 70% of patients.
  • Animal models exist for FALS, primarily for frequently mutated genes, aiding therapeutic development.

Purpose of the Study:

  • To review the current landscape of experimental treatments for FALS.
  • To highlight promising therapeutic strategies and ongoing clinical trials for FALS patients.

Main Methods:

  • Gene-specific therapies, including antisense oligonucleotides (ASO) delivered via viral vectors (AAV) targeting SOD1 mutations.
  • Antibody-based therapies targeting misfolded SOD1 protein.
  • Microbiota modulation as a therapeutic strategy, particularly for C9ORF72 models.

Main Results:

  • Gene-specific therapies, especially AAV9+anti-SOD1 ASO, have shown significant success in preventing or halting disease progression in animal models.
  • Antibody-based therapies are effective but less so than gene therapies, with epitope selection being a key challenge.
  • Microbiota modulation presents a safe and easily administered approach with promising results in C9ORF72 models.

Conclusions:

  • The field of experimental FALS treatment is rapidly advancing with promising results.
  • Several therapeutic strategies, including gene-specific and microbiota-based approaches, are under investigation in ongoing human clinical trials.
  • There is a significant unmet need for effective FALS treatments, driving innovation and research.