Amyotrophic Lateral Sclerosis (ALS)
Why in News?
- Amyotrophic Lateral Sclerosis (ALS) has been in the news in the last few days following new research linking occupational pesticide exposure with a higher risk of ALS, with a recent study reporting particularly elevated risk among heavily exposed workers.
- At the same time, advances in RNA-based therapies are attracting attention, with Ractigen Therapeutics reporting completion of enrolment and first dosing in a Phase-II trial of RAG-17 for SOD1-associated ALS on 6 August 2026.
What is ALS?
- Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease in which motor neurons responsible for voluntary muscle movement gradually degenerate and die.
- It affects upper and lower motor neurons, resulting in progressive muscle weakness, loss of movement, difficulty speaking and swallowing, and eventually respiratory muscle failure.
- ALS is also commonly called Motor Neuron Disease (MND), although the terminology and disease spectrum can vary across countries.
- Around 90% of ALS cases are sporadic, while approximately 10% are familial and associated with genetic mutations. Important genes include SOD1, C9orf72, TARDBP and FUS.
Pathophysiology
- Motor neuron degeneration: Death of neurons in the brain and spinal cord disrupts communication between the nervous system and skeletal muscles.
- Muscle atrophy: Loss of neural stimulation causes progressive wasting and weakness of muscles.
- Multiple mechanisms: Disease development may involve abnormal RNA processing, protein aggregation, oxidative stress, mitochondrial dysfunction, impaired autophagy, neuroinflammation and defective axonal transport.
- Cognitive function: ALS primarily affects motor functions, but some patients can also develop frontotemporal cognitive or behavioural changes.
Latest Research — 2026
- Environmental risk: A recent study reported that occupational exposure to pesticides may be associated with substantially increased ALS risk, strengthening interest in environmental contributors to neurodegenerative diseases.
- RNA-based therapy: RAG-17 is being investigated for SOD1-associated ALS, representing the growing application of RNA-targeting approaches to genetically defined forms of the disease.
- AI and digital biomarkers: Researchers are increasingly investigating speech analysis and machine-learning models for early identification and monitoring of ALS progression, particularly because speech impairment can emerge from bulbar motor dysfunction.
Treatment & Management
- No definitive cure: Current treatment focuses on slowing disease progression, managing symptoms and maintaining quality of life.
- Approved therapies: FDA-recognised ALS treatments have included riluzole and edaravone, while tofersen provides a targeted treatment approach for patients with SOD1-associated ALS.
- Multidisciplinary care: Respiratory support, nutritional management, physiotherapy, speech therapy and assistive communication technologies are important components of care.
- RELYVRIO withdrawal: The earlier ALS drug sodium phenylbutyrate/taurursodiol (RELYVRIO) had its FDA approval withdrawn after its Phase-III PHOENIX trial failed to meet its specified endpoints.
