ALS Treatment Strategies

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ALS Treatment Strategies

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ALS Treatment Strategies

Overview

<table class="infobox infobox-therapeutic">
<tr>
<th class="infobox-header" colspan="2">ALS Treatment Strategies</th>
</tr>
<tr>
<td class="label">Target</td>
<td>Approach</td>
</tr>
<tr>
<td class="label">SOD1</td>
<td>ASO (tofersen)</td>
</tr>
<tr>
<td class="label">[C9orf72](/entities/c9orf72)</td>
<td>ASO candidates</td>
</tr>
<tr>
<td class="label">FUS</td>
<td>ASO candidates</td>
</tr>
<tr>
<td class="label">ATXN2</td>
<td>ASO (APB-101)</td>
</tr>
<tr>
<td class="label">Agent</td>
<td>Mechanism</td>
</tr>
<tr>
<td class="label">CNM-Au8</td>
<td>Catalytic gold nanocrystals</td>
</tr>
<tr>
<td class="label">Reldesemtiv</td>
<td>Fast skeletal muscle troponin activator</td>
</tr>
<tr>
<td class="label">Masitinib</td>
<td>Tyrosine kinase inhibitor</td>
</tr>
<tr>
<td class="label">Pridopidine</td>
<td>Dopamine stabilizer</td>
</tr>
<tr>
<td class="label">Trial</td>
<td>Intervention</td>
</tr>
<tr>
<td class="label">NCT05686534</td>
<td>Reldesemtiv</td>
</tr>
<tr>
<td class="label">NCT03162211</td>
<td>Masitinib</td>
</tr>
<tr>
<td class="label">NCT04482113</td>
<td>CNM-Au8</td>
</tr>
<tr>
<td class="label">NCT05270330</td>
<td>Combination therapy</td>
</tr>
</table>

...

ALS Treatment Strategies

Overview

<table class="infobox infobox-therapeutic">
<tr>
<th class="infobox-header" colspan="2">ALS Treatment Strategies</th>
</tr>
<tr>
<td class="label">Target</td>
<td>Approach</td>
</tr>
<tr>
<td class="label">SOD1</td>
<td>ASO (tofersen)</td>
</tr>
<tr>
<td class="label">[C9orf72](/entities/c9orf72)</td>
<td>ASO candidates</td>
</tr>
<tr>
<td class="label">FUS</td>
<td>ASO candidates</td>
</tr>
<tr>
<td class="label">ATXN2</td>
<td>ASO (APB-101)</td>
</tr>
<tr>
<td class="label">Agent</td>
<td>Mechanism</td>
</tr>
<tr>
<td class="label">CNM-Au8</td>
<td>Catalytic gold nanocrystals</td>
</tr>
<tr>
<td class="label">Reldesemtiv</td>
<td>Fast skeletal muscle troponin activator</td>
</tr>
<tr>
<td class="label">Masitinib</td>
<td>Tyrosine kinase inhibitor</td>
</tr>
<tr>
<td class="label">Pridopidine</td>
<td>Dopamine stabilizer</td>
</tr>
<tr>
<td class="label">Trial</td>
<td>Intervention</td>
</tr>
<tr>
<td class="label">NCT05686534</td>
<td>Reldesemtiv</td>
</tr>
<tr>
<td class="label">NCT03162211</td>
<td>Masitinib</td>
</tr>
<tr>
<td class="label">NCT04482113</td>
<td>CNM-Au8</td>
</tr>
<tr>
<td class="label">NCT05270330</td>
<td>Combination therapy</td>
</tr>
</table>

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting upper and lower motor [neurons](/entities/neurons), leading to muscle weakness, paralysis, and respiratory failure. Treatment strategies span symptomatic management, disease-modifying therapies, and emerging approaches targeting underlying molecular mechanisms. This page provides a comprehensive overview of current and developing ALS treatments. [@bensimon1994]

FDA-Approved Disease-Modifying Therapies

Riluzole (Rilutek)

Mechanism: Sodium channel blocker; glutamate excitotoxicity reduction
Dose: 50 mg twice daily
Efficacy: Extends survival by 2-3 months; modest functional benefit
Status: First FDA-approved ALS drug (1995)

Edaravone (Radicava)

Mechanism: Free radical scavenger; reduces oxidative stress
Dose: 60 mg IV infusion (10 days/month after loading)
Efficacy: Slows functional decline (33% reduction in ALSFRS-R decline)
Status: FDA-approved (2017)

AMX0035 (Relyvrio)

Mechanism: Combination of sodium phenylbutyrate and taurursodiol
Efficacy: Extended survival by 4.8 months; functional benefit
Dose: 1 packet daily (dissolved in water)
Status: FDA-approved (2022)

Tofersen (Qalsody)

Mechanism: Antisense oligonucleotide targeting SOD1 gene
Dose: 100 mg intrathecal injection every 2 weeks (4 doses, then monthly)
Efficacy: Reduces SOD1 protein and [neurofilament light](/biomarkers/neurofilament-light-chain-nfl) chain; functional benefit in SOD1 patients
Status: FDA-approved (2023) for SOD1-ALS

Symptomatic Treatments

Muscle Spasticity

Baclofen: GABA-B agonist; start 5-10 mg TID, titrate to 30-60 mg/day
Tizanidine: Alpha-2 adrenergic agonist; 2-8 mg TID
Benzodiazepines: Diazepam or clonazepam for severe spasticity

Muscle Cramps

Quinine sulfate: 200-300 mg at bedtime
Magnesium supplements: 250-500 mg daily
Physical therapy: Stretching exercises

Salivation

Glycopyrrolate: 1-2 mg TID
Scopolamine patch: 1.5 mg patch every 72 hours
Botulinum toxin: For refractory drooling

Dysarthria and Dysphagia

Speech therapy: Augmentative communication devices
Swallowing assessments: Prevent aspiration
Diet modifications: Thickened liquids, modified textures

Respiratory Support

Non-invasive ventilation (NIV): BiPAP for nocturnal hypoventilation
Assistive cough devices: Mechanical insufflation-exsufflation
Mechanical ventilation: For advanced disease

Emerging Disease-Modifying Therapies

Gene Therapies

Neuroprotective Agents

Anti-Aggregation Strategies

Small molecules: Targeting [TDP-43](/mechanisms/tdp-43-proteinopathy) aggregates
[Autophagy](/entities/autophagy) enhancers: Rapamycin, trehalose
Antibodies: Anti-aggregate immunotherapies

Stem Cell Therapies

Neural stem cells: Phase 1/2 trials ongoing
MSC therapy: Immunomodulation; Phase 2 trials
iPSC-derived motor neurons: Preclinical

Clinical Trials Landscape

Active Phase 3 Trials

Biomarkers in Development

Neurofilament light chain (NfL): Blood biomarker for disease progression
ALS-related proteins: SOD1, TDP-43, FUS in CSF
Neuroimaging: PET and MRI for disease monitoring

Multi-Disciplinary Care

Standard of Care Components

Neurology: Disease management and medication

Pulmonology: Respiratory assessment and support

Physical therapy: Mobility and function

Occupational therapy: Daily activities adaptation

Speech therapy: Communication and swallowing

Nutrition: Dietary support and PEG placement

Psychology: Mental health support

Social work: Care coordination

Clinical Guidelines

EFNS Guidelines: European evidence-based guidelines
AAN Practice Parameters: American Academy of Neurology
International Alliance: ALS caregiver guidelines

Patient Stratification

Genetic Subtypes

SOD1-ALS: 15-20% of familial cases; tofersen approved
C9orf72-ALS: Most common genetic form (40% familial)
FUS-ALS: 5% of familial cases
Sporadic ALS: 90-95% of cases; no identified mutation

Personalized Medicine Approaches

Genetic testing: Increasingly recommended at diagnosis
Phenotypic subtyping: Bulbar vs. limb onset
Biomarker stratification: NfL levels for trial enrichment

External Links

[PubMed: ALS Treatment Strategies](https://pubmed.ncbi.nlm.nih.gov/?term=amyotrophic+lateral+sclerosis+treatment)
[ClinicalTrials.gov](https://clinicaltrials.gov)
[ALS Association](https://www.als.org/)
[ALS Therapy Development Institute](https://www.als.net/)

References

[Bensimon et al., Riluzole in ALS (1994) (1994)](https://doi.org/10.1016/S0140-6736(94)

[Sawada et al., Edaravone in ALS (2017) (2017)](https://doi.org/10.1001/jamaneurol.2017.0507)

[Paganoni et al., AMX0035 Trial (2020) (2020)](https://doi.org/10.1056/NEJMoa2002244)

[Miller et al., Tofersen for SOD1-ALS (2022) (2022)](https://doi.org/10.1056/NEJMoa2204705)

[Van Es et al., ALS disease modification (2023) (2023)](https://doi.org/10.1016/S0140-6736(23)

[Hardiman et al., ALS clinical management (2021) (2021)](https://doi.org/10.1038/s41582-021-00556-0)

Unknown, NCT05686534 Clinical Trial (n.d.)

[Lu et al., C9orf72 ASO therapy (2022) (2022)](https://doi.org/10.1038/s41593-022-01074-8)

[Benatar et al., Neurofilament biomarkers (2023) (2023)](https://doi.org/10.1016/S1474-4422(23)

[Goutman et al., Recent advances in ALS (2022) (2022)](https://doi.org/10.1016/j.neuron.2022.09.014)

From the [SciDEX Exchange](/exchange) — scored by multi-agent debate

[CYP46A1 Overexpression Gene Therapy](/hypothesis/h-2600483e) — <span style="color:#81c784;font-weight:600">0.79</span> · Target: CYP46A1
[Purinergic Signaling Polarization Control](/hypothesis/h-0758b337) — <span style="color:#81c784;font-weight:600">0.74</span> · Target: P2RY1 and P2RX7
[Transcriptional Autophagy-Lysosome Coupling](/hypothesis/h-ae1b2beb) — <span style="color:#81c784;font-weight:600">0.72</span> · Target: FOXO1
[Heat Shock Protein 70 Disaggregase Amplification](/hypothesis/h-5dbfd3aa) — <span style="color:#81c784;font-weight:600">0.71</span> · Target: HSPA1A
[Perforant Path Presynaptic Terminal Protection Strategy](/hypothesis/h-76888762) — <span style="color:#81c784;font-weight:600">0.69</span> · Target: PPARGC1A
[Lysosomal Calcium Channel Modulation Therapy](/hypothesis/h-8ef34c4c) — <span style="color:#81c784;font-weight:600">0.68</span> · Target: MCOLN1
[Chaperone-Mediated APOE4 Refolding Enhancement](/hypothesis/h-637a53c9) — <span style="color:#81c784;font-weight:600">0.67</span> · Target: HSPA1A, HSP90AA1, DNAJB1, FKBP5
[Metabolic Circuit Breaker via Lipid Droplet Modulation](/hypothesis/h-3d993b5d) — <span style="color:#81c784;font-weight:600">0.66</span> · Target: PLIN2

Related Analyses:

[Microglial subtypes in neurodegeneration — friend vs foe](/analysis/SDA-2026-04-02-gap-microglial-subtypes-20260402004119) 🔄
[TDP-43 phase separation therapeutics for ALS-FTD](/analysis/SDA-2026-04-01-gap-006) 🔄
[RNA binding protein dysregulation across ALS FTD and AD](/analysis/SDA-2026-04-01-gap-v2-68d9c9c1) 🔄
[CRISPR-based therapeutic approaches for neurodegenerative diseases](/analysis/SDA-2026-04-02-gap-crispr-neurodegeneration-20260402) 🔄

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Related Entities

therapeutics-als-treatment-strategies

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📊 Evidence Profile Foundational

Evidence Balance

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Certainty

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Debates

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Incoming

229

Outgoing

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📗 Cite This Artifact

ALS Treatment Strategies

ALS Treatment Strategies

Overview

ALS Treatment Strategies

Overview

FDA-Approved Disease-Modifying Therapies

Riluzole (Rilutek)

Edaravone (Radicava)

AMX0035 (Relyvrio)

Tofersen (Qalsody)

Symptomatic Treatments

Muscle Spasticity

Muscle Cramps

Salivation

Dysarthria and Dysphagia

Respiratory Support

Emerging Disease-Modifying Therapies

Gene Therapies

Neuroprotective Agents

Anti-Aggregation Strategies

Stem Cell Therapies

Clinical Trials Landscape

Active Phase 3 Trials

Biomarkers in Development

Multi-Disciplinary Care

Standard of Care Components

Clinical Guidelines

Patient Stratification

Genetic Subtypes

Personalized Medicine Approaches

See Also

External Links

References

💬 Discussion

📗 Cite This Artifact

ALS Treatment Strategies

ALS Treatment Strategies

Overview

ALS Treatment Strategies

Overview

FDA-Approved Disease-Modifying Therapies

Riluzole (Rilutek)

Edaravone (Radicava)

AMX0035 (Relyvrio)

Tofersen (Qalsody)

Symptomatic Treatments

Muscle Spasticity

Muscle Cramps

Salivation

Dysarthria and Dysphagia

Respiratory Support

Emerging Disease-Modifying Therapies

Gene Therapies

Neuroprotective Agents

Anti-Aggregation Strategies

Stem Cell Therapies

Clinical Trials Landscape

Active Phase 3 Trials

Biomarkers in Development

Multi-Disciplinary Care

Standard of Care Components

Clinical Guidelines

Patient Stratification

Genetic Subtypes

Personalized Medicine Approaches

See Also

External Links

References

Related Hypotheses

💬 Discussion