Erfan Bashar
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ALS — Treatment

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Educational scope notice: This is a study note for medical students, not medical advice, diagnosis, or treatment guidance. Clinical management should follow local protocols and current guidelines.

There is no cure for ALS. Treatment rests on two pillars: disease-modifying pharmacotherapy, which modestly slows progression, and multidisciplinary symptomatic management, which preserves quality of life. Average survival from symptom onset is 3–4 years in classical ALS, though some phenotypes survive far longer, and respiratory and nutritional support extends survival.

Disease-modifying drugs

Riluzole

Riluzole, approved in 1995, was the first drug for ALS. It targets glutamate excitotoxicity: excess synaptic glutamate overstimulates motor neurons, admitting calcium and killing the cell. Riluzole inhibits presynaptic glutamate release, reducing this stress. Trials showed roughly 3 months of extended survival. Observational series have reported longer real-world extensions, though these comparisons carry confounding. Liver function monitoring is recommended.

Edaravone

Edaravone is a free-radical scavenger (antioxidant) that reduces oxidative stress on motor neurons, with a small clinical benefit in selected patients. Originally intravenous, oral formulations have since become available in some regions. It is approved in the United States and Japan but has no marketing authorisation in Europe: the manufacturer withdrew its EU application in May 2019 during EMA assessment.

Sodium phenylbutyrate–taurursodiol (Relyvrio/AMX0035): approved then withdrawn

This combination addressed endoplasmic-reticulum stress and mitochondrial dysfunction in preclinical models. It received FDA approval in 2022 on phase 2 data showing slower functional decline, supported by strong patient-community advocacy. The subsequent global phase 3 PHOENIX trial did not meet its primary or secondary endpoints, and the manufacturer voluntarily removed the drug from the US and Canadian markets in 2024, with formal FDA withdrawal completed in 2025. Relyvrio is therefore a cautionary example: accelerated approval on early data does not guarantee confirmed benefit.

Tofersen

Tofersen is the first targeted treatment for a genetic cause of ALS: an antisense oligonucleotide for patients with SOD1 mutations, who account for roughly 2% of all ALS cases. It reduces SOD1 protein production and lowers neurofilament levels in cerebrospinal fluid, a marker of ongoing neuronal damage. The FDA granted accelerated approval in April 2023 on the basis of neurofilament reduction, with continued approval contingent on confirmatory trials. Treatment requires genetic confirmation of a SOD1 mutation and is given by repeated intrathecal administration with monitoring for adverse effects. A prevention trial in pre-symptomatic SOD1 carriers is testing whether early treatment delays onset.

Gene therapy: C9orf72

The C9orf72 hexanucleotide repeat expansion is the most common genetic cause of both ALS and frontotemporal dementia. Antisense therapy against C9orf72 has been less successful: a Biogen programme was discontinued in 2022 after early-phase results showed no efficacy signal.

Symptomatic management

Because disease-modifying therapy is limited, symptomatic care is the backbone of ALS management, delivered by a multidisciplinary team: neurologist, respiratory physician, speech therapist, dietitian, physiotherapist, occupational therapist, and psychologist.

Dysphagia and nutrition

Progressive dysphagia makes oral intake insufficient or unsafe. Percutaneous endoscopic gastrostomy (PEG) provides enteral nutrition directly into the stomach and should be planned early, ideally before respiratory function declines significantly, because the procedure carries higher risk once respiratory compromise is severe.

Respiratory support

Respiratory failure is the usual cause of death. Management is stepwise:

  1. Non-invasive ventilation (NIV) — typically started at night when nocturnal hypoventilation develops, then extended as daytime saturation declines. Masks are the standard interface; helmets suit patients who cannot tolerate masks.
  2. Cough assistance — mechanical insufflation-exsufflation to clear secretions.
  3. Tracheostomy with invasive ventilation — among the most survival-extending options but requiring fully equipped 24-hour home care. It must be a planned decision, never an emergency intervention by staff unfamiliar with the patient’s wishes. Preventing unwanted emergency tracheostomy through advance care planning is a central goal of ALS care.

Other symptoms

Three symptom groups have established treatments.

  • Sialorrhea and secretions. Anticholinergic drugs reduce saliva. Botulinum toxin injection into the salivary glands suits refractory cases. Assisted cough techniques clear retained bronchial secretions.
  • Cramps and spasticity. Stretching and physiotherapy come first. Baclofen or tizanidine treats troublesome spasticity.
  • Pseudobulbar affect. Sudden laughing or crying from corticobulbar pathway disruption responds to dextromethorphan–quinidine or SSRI treatment.

Cognition, behaviour, and communication

Roughly half of ALS patients experience cognitive or behavioural change and about 10% develop frontotemporal dementia, monitored with the Edinburgh Cognitive ALS Screen. Executive dysfunction has been associated with significantly shorter survival in cohort studies, plausibly because it complicates decisions about gastrostomy, ventilation, and tracheostomy. Eye movements are typically preserved until late disease, so eye-tracking technology sustains communication. Brain–computer interfaces remain investigational.

End-of-life planning

Discussing the diagnosis follows honesty combined with hope: truthful information directed toward support resources, with routine referral to psychological support. Key points for planning:

  • Patients may refuse gastrostomy, ventilation, or tracheostomy; these decisions are documented in advance and respected.
  • Continuous care needs are heavy, typically shared across several caregivers whose education and support are part of the plan.
  • Major depression is less common than often assumed, but anxiety and depression occur and need routine screening.

Disease monitoring

The ALS Functional Rating Scale–Revised (ALSFRS-R) has 12 items covering bulbar, fine motor, gross motor, and respiratory function. It is the standard instrument for tracking progression and evaluating drug efficacy and can be administered by phone or caregiver.

Anatomical and functional staging (King’s, MITOS) is taught alongside clinical phenotypes.

Evidence anchors

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