What is motor neuron disease?

Motor neuron disease (MND) encompasses a group of progressive neurological disorders causing degeneration of motor neurons — the nerve cells that control voluntary muscles. The most common form globally is amyotrophic lateral sclerosis (ALS, known as Lou Gehrig's disease in the US). ALS affects both upper (brain) and lower (brainstem and spinal cord) motor neurons — causing progressive limb weakness, muscle wasting, fasciculations, spasticity, bulbar symptoms (speech and swallowing difficulty) and respiratory failure. Most patients die from respiratory failure within 3-5 years of symptom onset.

ALS affects people of all ethnicities worldwide. It is slightly more common in men (1.5:1 male:female ratio, more equal in older patients). Onset is typically in the 50s-70s; onset before 40 is uncommon. Approximately 90% of cases are "sporadic" (no known family history); approximately 10% are familial (genetic). Risk factors for sporadic ALS are poorly understood — military service, certain pesticide exposures, heavy physical activity and smoking have been associated with modestly increased risk.

Is there a cure for ALS?

There is no cure. The available disease-modifying treatments provide modest benefits: riluzole (extends survival approximately 3 months); edaravone (slows functional decline in a specific rapidly progressing subset); AMX0035/Relyvrio (sodium phenylbutyrate + taurursodiol — extends survival approximately 6 months in CENTAUR trial). Tofersen — targeted only at SOD1-ALS — substantially reduces neurofilament biomarkers of neurodegeneration (a surrogate endpoint). None halt or meaningfully slow progression for most patients.

What is tofersen and why is it significant?

Tofersen (Qalsody) is the first targeted therapy for a specific ALS gene mutation — SOD1-ALS. It is an antisense oligonucleotide (ASO) that binds to SOD1 mRNA and promotes its degradation, reducing production of the toxic mutant SOD1 protein. Administered by lumbar puncture into the spinal fluid every 28 days. FDA granted accelerated approval in April 2023 based on reduction in neurofilament light chain (a biomarker of neuronal damage), though clinical benefit confirmation is ongoing. It represents the proof-of-concept that precision medicine approaches targeting specific genetic causes of ALS can work.

What is the connection between ALS and FTD?

ALS and frontotemporal dementia (FTD) are ends of a disease spectrum — approximately 15% of ALS patients also have FTD, and ALS motor features occur in some FTD patients. C9orf72 repeat expansion is the most common genetic cause of both ALS and FTD. TDP-43 protein aggregation is the pathological hallmark of most ALS (and many FTD cases). Understanding this ALS-FTD continuum has transformed research — with TDP-43 as a central therapeutic target.

How does ALS progress?

ALS typically begins focally — weakness in one limb or bulbar symptoms (speech, swallowing) — and spreads to affect adjacent body regions progressively. Limb-onset ALS (most common — approximately 70%) spreads from limbs to trunk and eventually to respiratory muscles. Bulbar-onset (approximately 25%) begins with dysarthria/dysphagia and progresses more rapidly to respiratory failure. Respiratory-onset ALS (rare — approximately 5%) presents with breathlessness. Cognitive impairment occurs in approximately 50% (ALS-mild cognitive impairment) and frank FTD in approximately 15%.

What is multidisciplinary ALS care?

Specialist multidisciplinary ALS care — combining neurology, respiratory medicine, physiotherapy, occupational therapy, speech and language therapy, dietetics, social work and palliative care — extends survival (by approximately 7-12 months compared to general neurology care) and dramatically improves quality of life. Key interventions: non-invasive ventilation (most impactful — extends survival 7-12 months); gastrostomy (PEG/RIG) for nutrition when swallowing fails; communication aids for bulbar patients; and advance care planning.

What did the Ice Bucket Challenge achieve?

The 2014 ALS Ice Bucket Challenge — viral social media campaign involving dumping ice water over oneself — raised over $220 million worldwide in weeks. The ALS Association's share ($115M) funded research that led to discovery of the NEK1 and C21orf2 ALS genes. It dramatically increased public awareness of ALS. It demonstrated that social media could mobilise unprecedented charitable funding for rare diseases. Subsequent campaigns have raised millions more — enabling clinical trials including CENTAUR (AMX0035).

How does GMJ News cover ALS/MND?

GMJ News covers WHO MND data, tofersen approval, AMX0035 evidence, multidisciplinary care standards, C9orf72 and SOD1 research, and emerging gene therapy approaches. ALS is part of the GMJ's neurological disease coverage — directly relevant to PHIG's neurological health priorities and the Georgian Medical Journal.

Home › Topics › Motor Neuron Disease (ALS)

Motor Neuron Disease (ALS)

GMJ News knowledge hub · last reviewed September 2026 · Georgian Medical Journal

Summary Statistics Glossary GMJ news FAQ Documents Organizations Research

Motor neuron disease (MND) — most commonly amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease) — is a progressive neurodegenerative disease destroying both upper and lower motor neurons, causing progressive paralysis affecting limb, bulbar and respiratory function: approximately 200,000 people are living with ALS globally at any time, with most dying within 3-5 years of diagnosis (WHO). ALS has no cure — riluzole modestly extends survival; edaravone and AMX0035 slow functional decline. The 2023 approval of tofersen — the first targeted therapy for SOD1-ALS — marks the beginning of precision medicine for genetic MND subtypes.

Key messages

200,000 living with ALS globally

Amyotrophic lateral sclerosis (ALS) — the most common form of motor neuron disease (MND) — affects approximately 200,000 people at any time globally, with 30,000 new cases per year. ALS kills most patients within 3-5 years of diagnosis (WHO/MND Association).

No cure — modestly effective treatments

ALS has no cure. Riluzole (1995) modestly extends survival by approximately 3 months. Edaravone (2017) slows functional decline in a subset of patients. AMX0035 (2022) extends survival by approximately 6 months. None halt progression.

First precision medicine for SOD1-ALS

Tofersen — an antisense oligonucleotide targeting mutant SOD1 protein — received FDA accelerated approval in 2023 for SOD1-ALS (approximately 2% of ALS cases). It substantially reduces neurofilament biomarkers of neuronal damage and slows disease progression, representing the first targeted therapy for a specific ALS gene mutation.

Multidisciplinary care extends survival

While no drug dramatically alters ALS course, multidisciplinary specialist care — neurologist, physiotherapist, speech therapist, dietitian, respiratory team, social worker, palliative care — significantly extends survival and quality of life.

Genetic forms 10%

Approximately 10% of ALS is familial (FALS) — caused by mutations in genes including SOD1, C9orf72 (most common, also causing frontotemporal dementia), TARDBP, FUS and others. Genetic testing is recommended for all patients.

Ice Bucket Challenge — a fundraising revolution

The 2014 ALS Ice Bucket Challenge raised over $220 million globally — dramatically increasing ALS research funding and leading to the discovery of multiple new ALS genes and research advances. It demonstrated the power of social media for health fundraising.

Key statistics

200K

people living with ALS globally

WHO/MND Association

3-5yr

median survival from diagnosis

WHO

30K

new ALS cases/year globally

GBD

10%

of ALS is familial (genetic)

WHO/research

2023

year of tofersen FDA approval for SOD1-ALS

FDA

~6mth

survival extension with AMX0035 (Relyvrio)

CENTAUR trial

ALS/MND incidence per 100,000 population by age group — global epidemiology

Source: Published epidemiological data. ALS incidence peaks in the 60s-70s; rare below 40.

Glossary of key terms

ALS (Amyotrophic lateral sclerosis)
WHOA progressive neurodegenerative disease causing death of both upper motor neurons (in brain) and lower motor neurons (in brainstem and spinal cord) — leading to progressive weakness, wasting, fasciculations, spasticity and eventually complete paralysis. Respiratory failure is the primary cause of death.

SOD1
ResearchSuperoxide dismutase 1 — the first ALS gene identified (1993). SOD1 mutations cause approximately 2% of ALS (but 20% of familial ALS). Mutant SOD1 protein misfolds and is toxic to motor neurons. Tofersen — an ASO targeting SOD1 mRNA — is the first approved targeted ALS therapy for SOD1-ALS.

C9orf72
ResearchThe most common ALS and FTD genetic cause — a hexanucleotide repeat expansion in chromosome 9 causing approximately 10% of all ALS. Often associated with frontotemporal dementia (FTD) — "ALS-FTD overlap." Antisense oligonucleotides targeting C9orf72 are in trials.

Riluzole
FDA/WHO EMLThe first disease-modifying ALS treatment (1995) — an antiglutamatergic agent that modestly reduces neuronal excitotoxicity, extending median survival by approximately 3 months. On the WHO Essential Medicines List. Now also available in a liquid form (Tiglutik) for patients with swallowing difficulties.

Tofersen (Qalsody)
FDA 2023An antisense oligonucleotide (ASO) targeting SOD1 mRNA — reducing mutant SOD1 protein production. FDA accelerated approval (April 2023) for ALS in adults with a confirmed SOD1 mutation. Administered intrathecally (into spinal fluid) every 28 days. First precision medicine for a defined ALS genotype.

NIV (non-invasive ventilation)
WHO/EANRespiratory support using a mask interface (BiPAP or similar) — the most impactful symptomatic intervention in ALS, extending survival by 7-12 months and dramatically improving quality of life. Offered when respiratory function (FVC) falls below approximately 50% predicted.