Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting upper and lower motor neurons, leading to muscle weakness, paralysis, and respiratory failure. Treatment strategies span symptomatic management, disease-modifying therapies, and emerging approaches targeting underlying molecular mechanisms. This page provides a comprehensive overview of current and developing ALS treatments.
- Mechanism: Sodium channel blocker; glutamate excitotoxicity reduction
- Dose: 50 mg twice daily
- Efficacy: Extends survival by 2-3 months; modest functional benefit
- Status: First FDA-approved ALS drug (1995)
- Mechanism: Free radical scavenger; reduces oxidative stress
- Dose: 60 mg IV infusion (10 days/month after loading)
- Efficacy: Slows functional decline (33% reduction in ALSFRS-R decline)
- Status: FDA-approved (2017)
- Mechanism: Combination of sodium phenylbutyrate and taurursodiol
- Efficacy: Extended survival by 4.8 months; functional benefit
- Dose: 1 packet daily (dissolved in water)
- Status: FDA-approved (2022)
- Mechanism: Antisense oligonucleotide targeting SOD1 gene
- Dose: 100 mg intrathecal injection every 2 weeks (4 doses, then monthly)
- Efficacy: Reduces SOD1 protein and neurofilament light chain; functional benefit in SOD1 patients
- Status: FDA-approved (2023) for SOD1-ALS
- Baclofen: GABA-B agonist; start 5-10 mg TID, titrate to 30-60 mg/day
- Tizanidine: Alpha-2 adrenergic agonist; 2-8 mg TID
- Benzodiazepines: Diazepam or clonazepam for severe spasticity
- Quinine sulfate: 200-300 mg at bedtime
- Magnesium supplements: 250-500 mg daily
- Physical therapy: Stretching exercises
- Glycopyrrolate: 1-2 mg TID
- Scopolamine patch: 1.5 mg patch every 72 hours
- Botulinum toxin: For refractory drooling
¶ Dysarthria and Dysphagia
- Speech therapy: Augmentative communication devices
- Swallowing assessments: Prevent aspiration
- Diet modifications: Thickened liquids, modified textures
- Non-invasive ventilation (NIV): BiPAP for nocturnal hypoventilation
- Assistive cough devices: Mechanical insufflation-exsufflation
- Mechanical ventilation: For advanced disease
| Target | Approach | Development Stage |
|--------|----------|-------------------|
| SOD1 | ASO (tofersen) | Approved |
| C9orf72 | ASO candidates | Phase 1/2 |
| FUS | ASO candidates | Preclinical |
| ATXN2 | ASO (APB-101) | Phase 1/2 |
| Agent | Mechanism | Phase |
|-------|-----------|-------|
| CNM-Au8 | Catalytic gold nanocrystals | Phase 2 |
| Reldesemtiv | Fast skeletal muscle troponin activator | Phase 3 |
| Masitinib | Tyrosine kinase inhibitor | Phase 3 |
| Pridopidine | Dopamine stabilizer | Phase 2 |
- Small molecules: Targeting TDP-43 aggregates
- Autophagy enhancers: Rapamycin, trehalose
- Antibodies: Anti-aggregate immunotherapies
- Neural stem cells: Phase 1/2 trials ongoing
- MSC therapy: Immunomodulation; Phase 2 trials
- iPSC-derived motor neurons: Preclinical
¶ Clinical Trials Landscape
| Trial |
Intervention |
Primary Outcome |
| NCT05686534 |
Reldesemtiv |
Change in ALSFRS-R |
| NCT03162211 |
Masitinib |
Change in ALSFRS-R |
| NCT04482113 |
CNM-Au8 |
Survival/ventilation-free |
| NCT05270330 |
Combination therapy |
Safety and efficacy |
- Neurofilament light chain (NfL): Blood biomarker for disease progression
- ALS-related proteins: SOD1, TDP-43, FUS in CSF
- Neuroimaging: PET and MRI for disease monitoring
¶ Standard of Care Components
- Neurology: Disease management and medication
- Pulmonology: Respiratory assessment and support
- Physical therapy: Mobility and function
- Occupational therapy: Daily activities adaptation
- Speech therapy: Communication and swallowing
- Nutrition: Dietary support and PEG placement
- Psychology: Mental health support
- Social work: Care coordination
- EFNS Guidelines: European evidence-based guidelines
- AAN Practice Parameters: American Academy of Neurology
- International Alliance: ALS caregiver guidelines
- SOD1-ALS: 15-20% of familial cases; tofersen approved
- C9orf72-ALS: Most common genetic form (40% familial)
- FUS-ALS: 5% of familial cases
- Sporadic ALS: 90-95% of cases; no identified mutation
- Genetic testing: Increasingly recommended at diagnosis
- Phenotypic subtyping: Bulbar vs. limb onset
- Biomarker stratification: NfL levels for trial enrichment