Amyotrophic lateral sclerosis (ALS): an animated, cited guide

This page needs JavaScript for its animations. The outline and key answers are below, and every claim in the full version carries a numbered citation.

Not medical advice. ALS Companion is an educational synthesis of published literature. It does not replace a clinician.

What is in it

What ALS is Who gets it, the numbers, and the ways it starts.
Upper and lower motor neurons Two neurons, two sets of signs, animated.
TDP-43 and what goes wrong A protein leaves the nucleus and clumps.
Genes: C9orf72, SOD1 and more Familial ALS, repeat expansions and genetic testing.
Diagnosis and criteria The Gold Coast, revised El Escorial and Awaji criteria, as a calculator.
The differential Conditions that can look like ALS, and how they differ.
ALSFRS-R and the course The 12-item scale, the progression rate and the stages.
Riluzole, edaravone and others What each drug targets and what the trials found.
Tofersen An antisense drug that lowers SOD1, for SOD1-ALS.
Breathing and NIV Weak breathing muscles, the tests, and when ventilation is offered.
Swallowing and feeding tubes Why weight matters and when a gastrostomy is discussed.
Living with ALS Communication, cognition, symptoms, planning and end of life.
Nursing care Assessment, giving the medicines, teaching and documentation.
Toward a cure Every route under study, with the evidence for each.
History and people From Charcot to tofersen.
Flashcards, quiz and glossary Revision for students.
Sources Every reference behind the guide.

Part 4 · Living & the future

Toward a cure

Researchers are trying to slow, stop or prevent ALS at every step from the faulty gene to the weakening muscle. Press Play to move along the pathway; each step lights the routes that act there. Use the filter to show only routes with one evidence label. The route cards below give the trial numbers and their status on ClinicalTrials.gov. Nothing here is advice to any reader.

Pathway

Schematic pathway, not to scale.

Reading the labels. Established a randomised trial or a regulatory approval shows an effect on a biomarker or a clinical outcome. Early evidence case series, small or uncontrolled early human data, or a positive topline result not yet peer reviewed. Hypothesis laboratory or animal data only. Tested and negative an adequately sized randomised trial, or a registry termination, showed no benefit. ALS has a long history of promising phase 2 results that then failed in phase 3. ⁵⁶

Route by route

Trial status and last-update dates as read from ClinicalTrials.gov on 20 October 2026. The filter above also applies here.

About the FUS result. The FUSION phase 3 topline of 22 September 2026 comes from a news report of the companies' announcement. It is not peer reviewed. The report gives a P value for the primary endpoint but no effect sizes, and ulefnersen is not approved anywhere. ³⁹⁴

Open questions

Gaps that recent reviews name themselves. Each is a place where a study could change the picture.

Unproven stem-cell clinics

What published guidance says

A JAMA Neurology viewpoint describes "stem cell tourism" as an Internet-based industry that sells unproven procedures to people with incurable neurological diseases, including ALS, with a risk of illness and death. It calls on medical societies and licensing boards to address it. ⁷²

The International Society for Stem Cell Research (ISSCR) guide warns about treatments that have not undergone proper testing or regulatory approval and are marketed by clinics. It encourages caution and decisions taken together with treating clinicians. ²⁴⁴

Under trial conditions, the cell therapy NurOwn did not meet its phase 3 primary endpoint. ¹²⁹

In plain wordsSome clinics sell stem-cell treatments for ALS that have not been properly tested. Guidance from experts is to be cautious and to talk any offer through with the treating team first.

The big picture

About 97% of all ALS has TDP-43 accumulation. For sporadic ALS, a 2026 review calls today's disease-modifying therapies "of limited utility", which is why gene-specific routes have produced the first targeted successes. ¹⁶⁶

A 2022 Lancet Seminar noted that most recent advances "have yet to translate into patient benefit". ¹⁸⁰

Exam hookGene-specific ALS (SOD1, FUS) is where targeted therapy has worked first; most ALS is sporadic and TDP-43-driven. ¹⁶⁶

In plain wordsResearchers are trying many routes. A few work for small genetic groups, and none yet for most people with ALS.