Evidence map›Paper›PMID 26929355›Full record

Trial reportProceedings of the National Academy of Sciences of the United States of America2016

Acetylcholine receptors from human muscle as pharmacological targets for ALS therapy.

Eleonora Palma, Jorge Mauricio Reyes-Ruiz, Diego Lopergolo, Cristina Roseti, Cristina Bertollini, Gabriele Ruffolo, Pierangelo Cifelli, Emanuela Onesti, Cristina Limatola, Ricardo Miledi and 1 more

Registry-linked trialOpen access · bronzeAbstract readComparative StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03618966 (Neuromuscular Magnetic Stimulation Counteracts Muscle Decline in ALS Patients), which is not on this map. Cited by 38 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed, 1 pooled it
3.6field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

NCT03618966 phase2completednot on this map

Neuromuscular Magnetic Stimulation Counteracts Muscle Decline in ALS Patients

TypeinterventionalSponsorUniversity of Roma La SapienzaRan2014 to 2017Enrolled22ConditionsAmyotrophic Lateral SclerosisArmsNeuromuscular magnetic stimulation (NMMS)
3 · Its place in the literature

Who cites it

38 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Co-ultramicronized palmitoylethanolamide/luteolin normalizes GABAClinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology · 2023
    Trial
  4. Trial
  5. Trial
  6. Article
  7. Review
  8. Review
  9. Article
  10. Article
  11. Review
  12. Article
  13. Aberrant evoked calcium signaling and nAChR cluster morphology in aFrontiers in cell and developmental biology · 2024
    Article
  14. Review
  15. Article
  16. Review
  17. The "www" ofMembranes · 2022
    Review
  18. Review
  19. Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 5 institutions in 3 countries.

Eleonora PalmaDepartment of Physiology and Pharmacology, Istituto Pasteur-Fondazione Cenci Bolognetti, University of Rome Sapienza, 00185 Rome, Italy; Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Pisana, 00166 Rome, Italy; eleonora.palma@uniroma1.it rmiledi@uci.edu.
Jorge Mauricio Reyes-RuizDepartment of Neurobiology and Behavior, University of California, Irvine, CA 92697;
Diego LopergoloDepartment of Neurology and Psychiatry, University of Rome Sapienza, 00185 Rome, Italy;
Cristina RosetiIstituto di Ricovero e Cura a Carattere Scientifico San Raffaele Pisana, 00166 Rome, Italy;
Cristina BertolliniDepartment of Physiology and Pharmacology, Istituto Pasteur-Fondazione Cenci Bolognetti, University of Rome Sapienza, 00185 Rome, Italy;
Gabriele RuffoloDepartment of Physiology and Pharmacology, Istituto Pasteur-Fondazione Cenci Bolognetti, University of Rome Sapienza, 00185 Rome, Italy;
Pierangelo CifelliDepartment of Physiology and Pharmacology, Istituto Pasteur-Fondazione Cenci Bolognetti, University of Rome Sapienza, 00185 Rome, Italy; Ri.MED Foundation, 90133 Palermo, Italy;
Emanuela OnestiDepartment of Neurology and Psychiatry, University of Rome Sapienza, 00185 Rome, Italy;
Cristina LimatolaDepartment of Physiology and Pharmacology, Istituto Pasteur-Fondazione Cenci Bolognetti, University of Rome Sapienza, 00185 Rome, Italy; Istituto di Ricovero e Cura a Carattere Scientifico Neuromed, 86077 Pozzilli, Isernia, Italy;
Ricardo MilediDepartment of Neurobiology and Behavior, University of California, Irvine, CA 92697; Instituto de Neurobiología, Universidad Nacional Autónoma de México, Juriquilla, 76230 Querétaro, México eleonora.palma@uniroma1.it rmiledi@uci.edu.
Maurizio InghilleriDepartment of Neurology and Psychiatry, University of Rome Sapienza, 00185 Rome, Italy;
Istituto Pasteur · ITSapienza University of Rome · ITIstituti di Ricovero e Cura a Carattere Scientifico · ITUniversity of California, Irvine · USIstituto Neurologico Mediterraneo · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting motor neurons that leads to progressive paralysis of skeletal muscle. Studies of ALS have revealed defects in expression of acetylcholine receptors (AChRs) in skeletal muscle that occur even in the absence of motor neuron anomalies. The endocannabinoid palmitoylethanolamide (PEA) modified the clinical conditions in one ALS patient, improving muscle force and respiratory efficacy. By microtransplanting muscle membranes from selected ALS patients into Xenopus oocytes, we show that PEA reduces the desensitization of acetylcholine-evoked currents after repetitive neurotransmitter application (i.e., rundown). The same effect was observed using muscle samples from denervated (non-ALS) control patients. The expression of human recombinant α1β1γδ (γ-AChRs) and α1β1εδ AChRs (ε-AChRs) in Xenopus oocytes revealed that PEA selectively affected the rundown of ACh currents in ε-AChRs. A clear up-regulation of the α1 subunit in muscle from ALS patients compared with that from non-ALS patients was found by quantitative PCR, but no differential expression was found for other subunits. Clinically, ALS patients treated with PEA showed a lower decrease in their forced vital capacity (FVC) over time as compared with untreated ALS patients, suggesting that PEA can enhance pulmonary function in ALS. In the present work, data were collected from a cohort of 76 ALS patients and 17 denervated patients. Our results strengthen the evidence for the role of skeletal muscle in ALS pathogenesis and pave the way for the development of new drugs to hamper the clinical effects of the disease.

Indexed as

Molecular Targeted TherapyAction PotentialsAdultAgedAged, 80 and overAmidesAmyotrophic Lateral SclerosisAnimalsCell MembraneEthanolaminesFemaleHumansMaleMicroinjectionsMiddle AgedMuscle DenervationAmidesCHRNE protein, humanCHRNG protein, humanEthanolaminespalmidrolPalmitic AcidsReceptors, NicotinicRecombinant Fusion ProteinsALSmicrotransplantationmuscle AChRqPCRXenopus oocytes

Identifiers

PMID26929355
PMCPMC4801305
OpenAlexW2288912078

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.