Amyotrophic Lateral Sclerosis (ALS)

•RCT evidence— Limited effective therapies; mostly supportive

What it is

ALS is a relentless progressive neurodegenerative disease of upper and lower motor neurons. Patients lose voluntary muscle control while sensation and cognition (in most) are preserved. Death usually from respiratory failure.

Genetics and aging biology

• ~10% are familial; the rest sporadic.
• C9orf72 hexanucleotide expansion is the most common cause (familial and sporadic).
• SOD1, TARDBP, FUS, others contribute.
• ALS shares pathways with normal aging biology: proteostasis collapse, RNA dysregulation, oxidative stress, mitochondrial dysfunction.
• Average onset 55–65 — an age-related disease at the population level.

Current treatments

• Riluzole: ~3-month survival extension.
• Edaravone: ~30% slower functional decline in selected patients.
• Sodium phenylbutyrate / taurursodiol (Relyvrio): withdrawn from US market 2024 after Phase 3 failure.
• Tofersen: antisense oligonucleotide for SOD1-ALS; first precision-medicine ALS drug, accelerated FDA approval 2023.

Care

• Multidisciplinary ALS clinic care extends survival and quality of life.
• Non-invasive ventilation extends survival.
• Gastrostomy for nutritional support.
• Communication-augmentation technology.
• Palliative-care integration.

Why ALS appears in a longevity reference

ALS is a window into proteostatic failure and motor-neuron biology that is relevant beyond ALS itself. Many therapeutic approaches developed for ALS (antisense oligonucleotides, autophagy enhancers, mitochondrial- function rescue) inform broader neurodegenerative-disease strategies.

Related entries

Loss of proteostasis, Mitochondrial dysfunction, Parkinson's disease.