Trial reportMedicine2018
Rapamycin treatment for amyotrophic lateral sclerosis: Protocol for a phase II randomized, double-blind, placebo-controlled, multicenter, clinical trial (RAP-ALS trial).
Trial report in Medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
71 citing papers in PubMed, 1 synthesis or guideline pooled it, 125 citations in OpenAlex.
- Emerging roles of ATG7 in human health and disease.EMBO molecular medicine · 2021Pooled it
- Randomized, double-blind, placebo-controlled trial of rapamycin in amyotrophic lateral sclerosis.Nature communications · 2023Trial
- mTOR Inhibition with Sirolimus in Multiple System Atrophy: A Randomized, Double-Blind, Placebo-Controlled Futility Trial and 1-Year Biomarker Longitudinal Analysis.Movement disorders : official journal of the Movement Disorder Society · 2022Trial
- Mitophagy in neuronal health and disease: from mechanisms to neurodegeneration.The Journal of clinical investigation · 2026Review
- Prion-like Protein TDP-43: Mechanisms, Diagnosis, and Therapeutic Prospects.Pathogens (Basel, Switzerland) · 2026Review
- Discovery of Novel Synthetic Cyclohexene-Based Small Molecules Targeting Senescence against Age-Related Pulmonary Fibrosis.Journal of medicinal chemistry · 2026Article
- From pathogenesis to therapy: the emerging role of regulatory T cells in amyotrophic lateral sclerosis.Journal of neuroinflammation · 2026Review
- Navigating the Autophagy Maze: ATG and Their Impact on Neurodegenerative Diseases.Molecular neurobiology · 2025Review
- Neuroinflammation and Amyotrophic Lateral Sclerosis: Recent Advances in Anti-Inflammatory Cytokines as Therapeutic Strategies.International journal of molecular sciences · 2025Review
- Immune mechanisms and shared immune targets in neurodegenerative diseases.Nature reviews. Neurology · 2025Review
- ALS: A Silent Slayer of Motor Neurons. Traditional Chinese Herbal Medicine as an Effective Therapy.Current pharmaceutical design · 2025Review
- Editorial: Community series in trends in neuroimmunology: cross-talk between brain-resident and peripheral immune cells in both health and disease, volume II.Frontiers in immunology · 2025Article
- Mitochondrial-targeted therapies in traumatic brain injury: From bench to bedside.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Drug Screening and Validation Targeting TDP-43 Proteinopathy for Amyotrophic Lateral Sclerosis.Aging and disease · 2024Review
- Pathophysiology of COVID-19-Related Extrapyramidal Disorders.Advances in experimental medicine and biology · 2024Review
- Tregs levels and phenotype modifications during Amyotrophic Lateral Sclerosis course.Frontiers in immunology · 2024Article
- Therapeutic targeting of ALS pathways: Refocusing an incomplete picture.Annals of clinical and translational neurology · 2023Review
- Novel therapeutic approaches to target neurodegeneration.British journal of pharmacology · 2023Review
- Neuro faces of beneficial T cells: essential in brain, impaired in aging and neurological diseases, and activated functionally by neurotransmitters and neuropeptides.Neural regeneration research · 2023Review
- Proteomics Analysis of Lymphoblastoid Cell Lines from Patients with Amyotrophic Lateral Sclerosis.Molecules (Basel, Switzerland) · 2023Article
11 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionMisfolded aggregated proteins and neuroinflammation significantly contribute to amyotrophic lateral sclerosis (ALS) pathogenesis, hence representing therapeutic targets to modify disease expression. Rapamycin inhibits mechanistic target of Rapamycin (mTOR) pathway and enhances autophagy with demonstrated beneficial effects in neurodegeneration in cell line and animal models, improving phenotype in SQSTM1 zebrafish, in Drosophila model of ALS-TDP, and in the TDP43 mouse model, in which it reduced neuronal loss and TDP43 inclusions. Rapamycin also expands regulatory T lymphocytes (Treg) and increased Treg levels are associated with slow progression in ALS patients.Therefore, we planned a randomized clinical trial testing Rapamycin treatment in ALS patients.
methodsRAP-ALS is a phase II randomized, double-blind, placebo-controlled, multicenter (8 ALS centers in Italy), clinical trial. The primary aim is to assess whether Rapamycin administration increases Tregs number in treated patients compared with control arm. Secondary aims include the assessment of safety and tolerability of Rapamycin in patients with ALS; the minimum dosage to have Rapamycin in cerebrospinal fluid; changes in immunological (activation and homing of T, B, NK cell subpopulations) and inflammatory markers, and on mTOR downstream pathway (S6RP phosphorylation); clinical activity (ALS Functional Rating Scale-Revised, survival, forced vital capacity); and quality of life (ALSAQ40 scale). DISCUSSION: Rapamycin potentially targets mechanisms at play in ALS (i.e., autophagy and neuroinflammation), with promising preclinical studies. It is an already approved drug, with known pharmacokinetics, already available and therefore with significant possibility of rapid translation to daily clinics. Findings will provide reliable data for further potential trials. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Committee of Azienda Ospedaliero Universitaria of Modena and by the Ethics Committees of participating centers (Eudract n. 2016-002399-28) based on the Helsinki declaration.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.