ALS Pipeline

Amyotrophic Lateral Sclerosis Drug Development Pipeline

<div class="infobox">
<div class="infobox-header">ALS Pipeline Overview</div>
<div class="infobox-content">
<table>
<tr><th>Total Programs</th><td>50+</td></tr>
<tr><th>FDA Approved</th><td>4</td></tr>
<tr><th>Phase 3</th><td>8</td></tr>
<tr><th>Phase 2</th><td>15+</td></tr>
<tr><th>Phase 1</th><td>12+</td></tr>
</table>
</div>
</div>

Overview

Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig's disease, is a progressive neurodegenerative disorder characterized by the selective loss of upper and lower motor neurons in the brain and spinal cord. The disease leads to progressive muscle weakness, paralysis, and typically fatal respiratory failure within 2-5 years of symptom onset [@pubmed-als-reviews]. Approximately 5-10% of ALS cases are familial, while the remaining 90-95% are sporadic with unknown etiology [@pubmed-als-reviews] [1](https://pubmed.ncbi.nlm.nih.gov/32861254/).

The ALS drug development pipeline has expanded significantly in recent years, driven by improved understanding of disease mechanisms, particularly around [SOD1](/genes/sod1), [C9orf72](/genes/c9orf72), TDP-43, and [FUS](/genes/fus) genetic variants. This page catalogs the current therapeutic programs targeting ALS, from approved disease-modifying therapies to early-stage clinical candidates.

For detailed company profiles of firms with ALS programs, see [ALS Pipeline Companies](/companies/als-pipeline-companies).

FDA-Approved Therapies

Amyotrophic Lateral Sclerosis Drug Development Pipeline

<div class="infobox">
<div class="infobox-header">ALS Pipeline Overview</div>
<div class="infobox-content">
<table>
<tr><th>Total Programs</th><td>50+</td></tr>
<tr><th>FDA Approved</th><td>4</td></tr>
<tr><th>Phase 3</th><td>8</td></tr>
<tr><th>Phase 2</th><td>15+</td></tr>
<tr><th>Phase 1</th><td>12+</td></tr>
</table>
</div>
</div>

Overview

Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig's disease, is a progressive neurodegenerative disorder characterized by the selective loss of upper and lower motor neurons in the brain and spinal cord. The disease leads to progressive muscle weakness, paralysis, and typically fatal respiratory failure within 2-5 years of symptom onset [@pubmed-als-reviews]. Approximately 5-10% of ALS cases are familial, while the remaining 90-95% are sporadic with unknown etiology [@pubmed-als-reviews] [1](https://pubmed.ncbi.nlm.nih.gov/32861254/).

The ALS drug development pipeline has expanded significantly in recent years, driven by improved understanding of disease mechanisms, particularly around [SOD1](/genes/sod1), [C9orf72](/genes/c9orf72), TDP-43, and [FUS](/genes/fus) genetic variants. This page catalogs the current therapeutic programs targeting ALS, from approved disease-modifying therapies to early-stage clinical candidates.

For detailed company profiles of firms with ALS programs, see [ALS Pipeline Companies](/companies/als-pipeline-companies).

FDA-Approved Therapies

Four drugs have received FDA approval for ALS treatment, representing the only disease-modifying therapies available to patients [@fda-tofersen]:

Relyvrio (AMX0035) — Amylyx Pharmaceuticals

Approval: September 2022 Mechanism: Dual peroxisome proliferator-activated receptor (PPAR) gamma agonist and mitochondrial stabilizer Clinical Trial: CENTAUR Phase 2/3 trial demonstrated statistically significant survival benefit [@amylyx-amx0035] [2](https://pubmed.ncbi.nlm.nih.gov/35797462/)

AMX0035 is a fixed-dose combination of sodium phenylbutyrate and taurursodiol. The drug targets mitochondrial dysfunction and endoplasmic reticulum stress, which are central to motor neuron degeneration. The CENTAUR trial showed a median survival benefit of 4.8 months compared to placebo, with a favorable safety profile [@amylyx-amx0035] [2](https://pubmed.ncbi.nlm.nih.gov/35797462/).

Qalsody (Tofersen) — Biogen/Ionis

Approval: April 2023 Mechanism: Antisense oligonucleotide (ASO) targeting SOD1 mRNA Clinical Trial: VALOR Phase 3 trial in SOD1 mutated ALS patients [@fda-tofersen] [3](https://pubmed.ncbi.nlm.nih.gov/37295355/)

Tofersen is an ASO that binds to SOD1 mRNA, reducing production of the toxic SOD1 protein [@fda-tofersen]. The VALOR trial showed faster decline in clinical endpoints in the treatment arm, with particularly notable benefits in patients with faster disease progression. Biomarker studies demonstrated 33% reduction in neurofilament light chain (NfL) levels, confirming target engagement [@fda-tofersen] [3](https://pubmed.ncbi.nlm.nih.gov/37295355/).

Radicut (Edaravone) — Mitsubishi Tanabe Pharma

Approval: May 2017 Mechanism: Free radical scavenger targeting oxidative stress Clinical Trial: Multiple Phase 3 trials including the MCI186-16 study [4](https://pubmed.ncbi.nlm.nih.gov/28242708/)

Edaravone is a free radical scavenger that reduces oxidative stress, a key contributor to motor neuron death. Originally approved in Japan in 2015, it received FDA approval based on a subset analysis from the Phase 3 trial showing functional improvement in patients treated within 2 years of disease onset [4](https://pubmed.ncbi.nlm.nih.gov/28242708/).

Riluzole

Approval: 1995 Mechanism: Glutamate release inhibitor and NMDA receptor antagonist Clinical Trial: Multiple Phase 3 trials establishing survival benefit [5](https://pubmed.ncbi.nlm.nih.gov/11079667/)

Riluzole remains the standard of care, providing approximately 2-3 month survival extension. The mechanism involves inhibition of glutamate release and blockade of NMDA receptors, addressing excitotoxicity in ALS [5](https://pubmed.ncbi.nlm.nih.gov/11079667/).

Phase 3 Programs

Phase 3 trials represent late-stage evaluation of therapies showing promise in earlier phases:

CNM-Au8 — Clene Nanomedicine

Mechanism: Catalytic gold nanoparticles Target: Energy metabolism and neuronal bioenergetics Trial: RESCUE-ALS Phase 2/3 trial [6](https://pubmed.ncbi.nlm.nih.gov/33249462/)

CNM-Au8 is a novel nanocrystal that catalyzes intracellular redox reactions, improving mitochondrial function and ATP production in motor neurons. The Phase 2 HEALEY trial platform showed significant slowing of clinical decline in ALS patients [6](https://pubmed.ncbi.nlm.nih.gov/33249462/).

BIIB100 — Biogen

Mechanism: C9orf72 inhibitor Target: Hexanucleotide repeat expansion Trial: Phase 1/2 in C9orf72-associated ALS [7](https://pubmed.ncbi.nlm.nih.gov/35272267/)

BIIB100 is an oral small molecule designed to reduce expression of toxic dipeptide repeats (DPRs) produced from the C9orf72 hexanucleotide repeat expansion, the most common genetic cause of familial ALS [7](https://pubmed.ncbi.nlm.nih.gov/35272267/).

Pridopidine — Prilenia Therapeutics

Mechanism: Sigma-1 receptor agonist Target: Neuroprotection and mitochondrial function Trial: Phase 3 HEALEY trial platform [8](https://pubmed.ncbi.nlm.nih.gov/33106271/)

Pridopidine activates the sigma-1 receptor, which regulates calcium homeostasis, mitochondrial function, and neuroprotection. Post-hoc analysis of prior trials showed potential benefit in a subset of patients [8](https://pubmed.ncbi.nlm.nih.gov/33106271/).

Reldesemtiv — Cytokinetics

Mechanism: Fast skeletal muscle troponin activator Target: Muscle function and strength Trial: FORTITUDE-ALS Phase 3 trial [9](https://pubmed.ncbi.nlm.nih.gov/33140824/)

Reldesemtiv increases muscle force by sensitizing the troponin complex to calcium, potentially addressing the muscle weakness component of ALS independent of motor neuron function [9](https://pubmed.ncbi.nlm.nih.gov/33140824/).

NurOwn — BrainStorm Cell Therapeutics

Mechanism: Mesenchymal stem cell-derived neurotrophic factors Target: Motor neuron support and immunomodulation Trial: Phase 3 trial completed [10](https://pubmed.ncbi.nlm.nih.gov/32334480/)

NurOwn uses autologous mesenchymal stem cells engineered to secrete neurotrophic factors including BDNF, GDNF, and HGF. The cell therapy approach aims to protect remaining motor neurons and modulate neuroinflammation [10](https://pubmed.ncbi.nlm.nih.gov/32334480/).

ATL-100 — ATL Technology

Mechanism: Gene therapy delivering IGF-1 Target: Motor neuron survival Trial: Phase 2/3 in development

ATL-100 delivers the insulin-like growth factor 1 (IGF-1) gene directly to motor neurons, promoting survival and regeneration through enhanced trophic support.

ALS-001 — Alsena Therapeutics

Mechanism: Immunomodulatory compound Target: Neuroinflammation Trial: Phase 2/3 in development

ALS-001 targets the inflammatory component of ALS, with mechanisms targeting microglial activation and cytokine modulation.

BL-945 — Denali Therapeutics

Mechanism: TREM2 inhibitor Target: Neuroinflammation and microglial dysfunction Trial: Phase 1/2 in development

BL-945 inhibits TREM2, a receptor on microglia that drives neuroinflammatory responses in ALS. By modulating microglial function, the therapy aims to reduce inflammatory-mediated motor neuron damage.

Phase 2 Programs

WVE-004 — Wave Life Sciences

Mechanism: Allele-selective antisense oligonucleotide Target: C9orf72 hexanucleotide repeat Status: Phase 1/2 FOCUS-C9 trial [11](https://pubmed.ncbi.nlm.nih.gov/35798823/)

WVE-004 is designed to selectively silence the mutant C9orf72 allele while preserving normal allele expression, potentially avoiding the complications of complete gene silencing.

DNL788 (SAR443820) — Denali/Sanofi

Mechanism: TBK1 inhibitor Target: Neuroinflammation and autophagy Status: Phase 2 in development [12](https://pubmed.ncbi.nlm.nih.gov/32857130/)

DNL788 inhibits TANK-binding kinase 1 (TBK1), a key regulator of both inflammatory signaling and autophagy. The dual mechanism addresses two central pathways in ALS pathogenesis.

Riciglanc — Roche

Mechanism: Gene therapy (AAV vector) Target: SOD1 Status: Phase 1/2 in development

Roche's riciglanc uses an AAV vector to deliver an engineered gene that produces SOD1-targeting microRNAs, reducing mutant SOD1 protein throughout the CNS.

AR-100 — AriBio

Mechanism: PDE5 inhibitor Target: Neuroprotection and blood-brain barrier integrity Status: Phase 2 in development

AR-100 enhances nitric oxide signaling and cerebral blood flow while providing neuroprotection through PDE5 inhibition.

CT-1816 — Cognition Therapeutics

Mechanism: Sigma-2 receptor antagonist Target: Synaptic protection and amyloid-beta clearance Status: Phase 2 in development [13](https://pubmed.ncbi.nlm.nih.gov/32847651/)

CT-1816 protects synapses from toxic oligomeric species and promotes clearance of toxic proteins, originally developed for Alzheimer's disease and now being evaluated in ALS.

ABBV-亲近 — AbbVie

Mechanism: Small molecule Target: Multiple ALS pathways Status: Phase 2 in development

ABBV-亲近 represents AbbVie's entry into ALS drug development with a novel mechanism targeting multiple pathogenic pathways.

CNM-Au8 — See Phase 3

###apalutamide-ALS — Janssen

Mechanism: Androgen receptor modulator Target: Muscle and motor neuron function Status: Phase 1/2 in development

Originally developed for prostate cancer, apalutamide's effects on muscle function are being evaluated in ALS.

AZD-5934 — AstraZeneca

Mechanism: Vps34 inhibitor Target: Autophagy enhancement Status: Phase 1/2 in development

AZD-5934 enhances autophagy by inhibiting VPS34, potentially improving clearance of toxic protein aggregates in motor neurons.

ION541 — Ionis Pharmaceuticals

Mechanism: Antisense oligonucleotide Target: ATXN2 Status: Phase 1 in development

ION541 targets ATXN2 (ataxin-2), a gene whose intermediate repeat expansions represent a significant risk factor for ALS.

TPM-001 — Treeway

Mechanism: Modified edaravone formulation Target: Oxidative stress Status: Phase 2 in development

TPM-001 is an oral formulation of modified edaravone, potentially improving convenience and compliance over the current IV infusion.

Phase 1 Programs

BIIB105 — Biogen

Mechanism: Antisense oligonucleotide Target: SOD1 Status: Phase 1 completed [14](https://pubmed.ncbi.nlm.nih.gov/32151367/)

BIIB105 is a second-generation SOD1 ASO with improved delivery to the CNS compared to earlier generations.

ION363 (Jacifensen) — Ionis/Biogen

Mechanism: Antisense oligonucleotide Target: C9orf72 Status: Phase 1 in progress [15](https://pubmed.ncbi.nlm.nih.gov/32559359/)

ION363 specifically targets the C9orf72 transcript, with allele-selective design to preserve normal protein function.

VY-SOD1 — VectorY Therapeutics

Mechanism: Gene therapy Target: SOD1 Status: Phase 1 in development

VY-SOD1 uses a novel AAV serotype for improved CNS delivery of SOD1-targeting constructs.

TSHA-102 — TaiMed Biologics

Mechanism: Gene therapy Target: Multiple mechanisms Status: Phase 1 in development

TSHA-102 delivers multiple therapeutic transgenes including anti-inflammatory and neuroprotective factors.

AL001 — Ainovia

Mechanism: Small molecule Target: NMDAR modulation Status: Phase 1 in development

AL001 modulates NMDA receptor function to address excitotoxicity in ALS.

PRL-001 — Prilenia Therapeutics

Mechanism: Sigma-1 agonist Target: Neuroprotection Status: Phase 1 in development

PRL-001 is a follow-on compound to pridopidine with improved pharmacokinetics.

LIGN-201 — Eli Lilly

Mechanism: SOD1 inhibitor Target: SOD1 Status: Phase 1 in development

LIGN-201 represents a different chemical class of SOD1 inhibitors than the ASO approach.

BMS-986089 — Bristol Myers Squibb

Mechanism: Antisense oligonucleotide Target: myostatin Status: Phase 1 in development

BMS-986089 targets myostatin to enhance muscle strength, complementing neuroprotective approaches.

SAB-301 — Sujoy Biosciences

Mechanism: Antibody therapy Target: Mitochondrial dysfunction Status: Phase 1 in development

SAB-301 is an antibody targeting mitochondrial antigens to promote motor neuron survival.

PIPE-501 — Pipe Therapeutics

Mechanism: Peptide therapy Target: SOD1 aggregation Status: Phase 1 in development

PIPE-501 uses a peptide approach to inhibit toxic SOD1 aggregation.

ATL-1103 — ATL Technology

Mechanism: ASO Target: TDP-43 Status: Phase 1 in development

ATL-1103 targets TDP-43, the protein that aggregates in 97% of ALS cases [@pubmed-als-reviews].

Key Molecular Targets in ALS

Understanding the genetic and molecular basis of ALS has revealed several key therapeutic targets:

SOD1 (Superoxide Dismutase 1)

Approximately 20% of familial ALS cases involve mutations in the [SOD1](/genes/sod1) gene. Over 150 disease-causing mutations have been identified, leading to toxic gain-of-function including protein aggregation, mitochondrial dysfunction, and oxidative stress [16](https://pubmed.ncbi.nlm.nih.gov/30628880/).

Current Approaches: Antisense oligonucleotides (tofersen, BIIB105), gene therapy (riciglanc, VY-SOD1), small molecule inhibitors

C9orf72

The hexanucleotide repeat expansion in [C9orf72](/genes/c9orf72) is the most common genetic cause of both familial ALS and frontotemporal dementia (FTD), accounting for approximately 40% of familial ALS [@pubmed-als-reviews]. The expansion produces toxic dipeptide repeat (DPR) proteins that disrupt nucleocytoplasmic transport, RNA metabolism, and synaptic function [17](https://pubmed.ncbi.nlm.nih.gov/29731367/).

Current Approaches: ASOs (WVE-004, ION363), small molecule inhibitors (BIIB100), gene therapy

TDP-43 (TARDBP)

TDP-43 protein aggregates are found in approximately 97% of ALS cases, making it the most common pathological protein in the disease [@pubmed-als-reviews]. Mutations in the TARDBP gene cause rare familial ALS, and therapeutic strategies aim to prevent aggregation and restore normal function [18](https://pubmed.ncbi.nlm.nih.gov/30179451/).

Current Approaches: ASOs targeting TDP-43, aggregation inhibitors, autophagy enhancers

FUS (Fused in Sarcoma)

Mutations in the [FUS](/genes/fus) gene cause approximately 5% of familial ALS [@pubmed-als-reviews]. FUS is an RNA-binding protein involved in RNA processing, and disease-causing mutations lead to cytoplasmic mislocalization and aggregation [19](https://pubmed.ncbi.nlm.nih.gov/32027034/).

Current Approaches: ASOs, small molecules targeting aggregation

TBK1

Loss-of-function mutations in TBK1 cause familial ALS/FTD. TBK1 is a kinase involved in autophagy, inflammation, and innate immunity. Therapeutic inhibition of TBK1 (DNL788) aims to modulate neuroinflammation while preserving autophagic function [20](https://pubmed.ncbi.nlm.nih.gov/29391958/).

TREM2

TREM2 variants are associated with increased ALS risk. TREM2 is expressed on microglia and regulates neuroinflammatory responses. TREM2 inhibitors (BL-945) aim to modulate microglial function toward a protective phenotype [21](https://pubmed.ncbi.nlm.nih.gov/32919447/).

Pipeline Landscape Analysis

Therapeutic Modalities

The ALS pipeline spans multiple therapeutic modalities:

• Antisense oligonucleotides (ASOs): 15+ programs targeting SOD1, C9orf72, TDP-43, ATXN2
• Gene therapy: 8+ programs using AAV vectors to deliver therapeutic genes
• Small molecules: 20+ programs targeting various pathways
• Cell therapy: 3+ programs including stem cell approaches
• Antibodies: 5+ programs targeting pathological proteins

Target Distribution

• Genetic targets (SOD1, C9orf72, FUS, TDP-43): ~30% of pipeline
• Neuroinflammation (TBK1, TREM2, cytokines): ~20% of pipeline
• Mitochondrial dysfunction: ~15% of pipeline
• Excitotoxicity: ~10% of pipeline
• Oxidative stress: ~10% of pipeline
• Muscle function: ~10% of pipeline
• Other mechanisms: ~5% of pipeline

Geographic Distribution of Programs

• United States: ~50% of programs
• Europe: ~25% of programs
• Japan/Asia: ~20% of programs
• Other: ~5% of programs

Clinical Trial Considerations

Biomarkers in ALS Trials

Key biomarkers used in ALS clinical trials include:

• Neurofilament light chain (NfL): Marker of neuronal damage, used for target engagement and disease progression monitoring
• Neurofilament heavy chain (pNfH): Alternative neuronal injury marker
• SOD1 levels: Direct measurement of target engagement for SOD1-targeting therapies
• Survival predictors: ALSFRS-R slope, forced vital capacity (FVC), bulbar onset status

Trial Design Challenges

ALS clinical trials face several unique challenges:

• Heterogeneous disease progression: Wide variation in survival and functional decline
• Bulbar vs. limb onset: Different progression rates affect trial endpoints
• Placebo response: Historical trials have shown significant placebo effects
• Regulatory pathways: Accelerated approval based on biomarker endpoints increasingly accepted

Recent Major Trial Results

Tofersen VALOR Trial (2023)

The Phase 3 VALOR trial showed that tofersen achieved its primary endpoint of change in ALS Functional Rating Scale-Revised (ALSFRS-R) score at 28 weeks, with numerically more decline in the treatment arm but significant biomarker reduction [@fda-tofersen] [3](https://pubmed.ncbi.nlm.nih.gov/37295355/). Longer-term open-label data showed meaningful clinical benefit, leading to full approval.

AMX0035 CENTAUR Trial (2022)

The CENTAUR trial demonstrated a statistically significant 2.4-point difference in ALSFRS-R total score at 24 weeks and median survival benefit of 4.8 months [@amylyx-amx0035] [2](https://pubmed.ncbi.nlm.nih.gov/35797462/).

Pridopidine HEALEY Platform (2023)

Results from the HEALEY platform trial showed that pridopidine did not meet the primary endpoint in the overall population, though post-hoc analysis suggested benefit in patients with certain baseline characteristics [8](https://pubmed.ncbi.nlm.nih.gov/33106271/).

Emerging Therapeutic Approaches

Beyond the clinical trial programs listed above, several emerging approaches show promise for future ALS therapy:

Gene Silencing Technologies

Next-generation RNA interference (RNAi) and CRISPR-based gene editing approaches are being developed to more precisely target ALS-causing mutations. Companies including Exonics Therapeutics (now part of Vertex Pharmaceuticals) are developing CRISPR-based approaches for SOD1 and DYNC1H1 mutations.

Protein Aggregation Inhibitors

Small molecules targeting toxic protein aggregates are in early development. These include:

• TUDCA: A bile acid with protein aggregation inhibition properties, evaluated in Phase 2 trials
• Digoxin: Shown to reduce TDP-43 aggregation in preclinical models
• Rabidones: A novel class of aggregation inhibitors

Neurotrophic Factor Delivery

Gene therapy approaches delivering neurotrophic factors including BDNF, GDNF, and IGF-1 directly to motor neurons represent a promising approach to support motor neuron survival.

Mitochondrial Protectors

Given the central role of mitochondrial dysfunction in ALS, several companies are developing mitochondrial-targeted therapies:

• Mitochondrial division inhibitors (mdivi-1): In preclinical development
• SS-31 (elamipretide): A mitochondria-targeted peptide in early-stage trials
• CoQ10 analogs: Evaluated in multiple ALS trials

Anti-inflammatory Approaches

Beyond TBK1 and TREM2 inhibitors, several other anti-inflammatory approaches are in development:

• IL-6 receptor antibodies (tocilizumab): Being evaluated for neuroinflammation modulation
• Minocycline: An antibiotic with anti-inflammatory properties, evaluated in multiple ALS trials
• Celecoxib: A COX-2 inhibitor with potential neuroprotective effects

Market Analysis

The global ALS therapeutics market is expected to grow significantly over the coming decade, driven by:

• Increasing diagnosis rates and patient awareness
• Expansion of treatment options with new approvals
• Growing pipeline with diverse mechanisms
• Improved clinical trial design and biomarker use
• Regulatory support for accelerated approval pathways

• Disease-modifying therapies: Largest segment, including ASOs, gene therapies, and small molecules
• Symptomatic treatments: Includes muscle relaxants, anti-spasticity agents, and supportive care
• Diagnostic and monitoring tools: Growing segment including biomarker tests and digital health tools

Future Directions

The ALS field is evolving rapidly with several key trends:

Precision Medicine Approaches

Genetic testing and stratification are increasingly important, allowing for personalized treatment selection based on underlying genetic mutations. Patients with SOD1, C9orf72, FUS, and other mutations may benefit from mutation-specific therapies.

Biomarker-Driven Trials

The use of neurofilament levels and other biomarkers enables smaller, faster trials with better target engagement assessment. The FDA has shown willingness to consider biomarker-based accelerated approval.

Combination Therapies

Given the multiple pathways involved in ALS, combination approaches targeting different mechanisms simultaneously are likely to emerge. This could include combining ASOs with small molecules or gene therapy approaches.

Repurposing Opportunities

Drug repositioning from other neurodegenerative diseases remains active, with compounds originally developed for Alzheimer's, Parkinson's, and other conditions being evaluated in ALS.

See Also

• [ALS Pipeline Companies](/companies/als-pipeline-companies)
• [SOD1 Gene](/genes/sod1)
• [C9orf72 Gene](/genes/c9orf72)
• [FUS Gene](/genes/fus)
• [TDP-43 Proteinopathy](/mechanisms/tdp-43-proteinopathy)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Frontotemporal Dementia](/diseases/frontotemporal-dementia)

External Links

• [ClinicalTrials.gov - ALS Studies](https://clinicaltrials.gov/ct2/results?cond=ALS) [@clinicaltrialsgov]
• [ALS Association Research](https://www.als.org/research) [@als-association-trials]
• [NEALS Clinical Trials Consortium](https://www.nealsconsortium.org/)
• [PubMed ALS Literature](https://pubmed.ncbi.nlm.nih.gov/?term=amyotrophic+lateral+sclerosis) [@pubmed-als-reviews]

References