DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for rippling muscle disease 2 — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleRippling muscle disease 2 maps to a 2-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for rippling muscle disease 2 is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
What the evidence adds up to
A 1996 case report describes a patient with rippling muscles and myasthenia gravis with thymoma. There was no family history of rippling muscle disease. The rippling resolved when the myasthenia gravis became florid. The patient was treated with pyridostigmine, prednisone, and plasmapheresis before thymectomy. The myasthenia gravis improved with treatment, and the rippling had not recurred four months after thymectomy. The authors suggest that rippling muscles may be triggered by an autoimmune phenomenon.
A 2024 review distinguishes hereditary rippling muscle disease (hRMD) from immune-mediated rippling muscle disease (iRMD). hRMD is caused by pathogenic variants in caveolin-3 (CAV3) or caveolae-associated protein 1 (CAVIN1/PTRF). CAV3-RMD presents a wide spectrum from asymptomatic creatine kinase elevation to severe muscle weakness. CAVIN1/PTRF-RMD includes congenital generalised lipodystrophy and extra-skeletal muscle manifestations. iRMD is often accompanied by other autoimmune disorders, including myasthenia gravis. Anti-cavin-4 antibodies are the serological marker. Most patients with iRMD respond to immunotherapy. A 1995 report notes that rippling muscle disease may be associated with intermittent esotropia, likely related to rippling of the medial recti.
A 2023 review of drug repositioning in muscular dystrophies states that muscular dystrophies have no cure, that medications and therapy can only help control symptoms and slow progression, and that effective treatments have yet to be developed despite knowledge of genetic origins and pathophysiology. It argues that drug repositioning is an accelerated method because safety, pharmacokinetic, and manufacturing data are already available, and that this is particularly important for patients with life-threatening illnesses who cannot wait for a conventional drug development cycle. No specific drug for rippling muscle disease is mentioned in any of the abstracts.
What is missing for rippling muscle disease is any controlled trial of a repurposed drug, any patient stratification by genetic subtype or immune status, and dedicated funding for a condition so rare that most evidence remains limited to case reports and reviews of the literature.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Archives of Neurology · 1996 · 55 citations
Rippling Muscles and Myasthenia Gravis With Rippling Muscles
AbstractOBJECTIVE: To describe a patient with rippling muscles and myasthenia gravis. DESIGN: Clinical, laboratory, electrophysiologic, and muscle biopsy data are reported. SETTING: Medical office and hospital. PATIENT: We describe a patient with rippling muscles (as seen in rippling muscle disease) and myasthenia gravis (MG) with thymoma. There was no family history of rippling muscle disease in our patient. Diplopia and other symptoms of MG were initially overshadowed by the striking rippling phenomenon. The rippling resolved when the MG became florrid. INTERVENTIONS: The patient was treated with pyridostigmine, prednisone, and plasmaphereses before removal of a thymoma. MAIN OUTCOME AND RESULTS: His MG improved with treatment and the rippling has not recurred 4 months after thymectomy. CONCLUSIONS: Rippling muscle disease is rare and usually inherited. Our patient with rippling muscles (but no family history of rippling muscle disease) and MG suggests that rippling muscles may also be triggered by an autoimmune phenomenon.
British Journal of Hospital Medicine · 2020 · 13 citations
Muscle wasting in the critically ill patient: how to minimise subsequent disability
AbstractMuscle wasting in critically ill patients is the most common complication associated with critical care. It has significant effects on physical and psychological health, mortality and quality of life. It is most severe in the first few days of illness and in the most critically unwell patients, with muscle loss estimated to occur at 2-3% per day. This muscle loss is likely a result of a reduction in protein synthesis relative to muscle breakdown, resulting in altered protein homeostasis. The associated weakness is associated with in an increase in both short- and long-term mortality and morbidity, with these detrimental effects demonstrated up to 5 years post discharge. This article highlights the significant impact that muscle wasting has on critically ill patients' outcomes, how this can be reduced, and how this might change in the future.
AbstractRippling muscle disease (RMD) is a rare disorder of muscle hyperexcitability. It is characterized by rippling wave-like muscle contractions induced by mechanical stretch or voluntary contraction followed by sudden stretch, painful muscle stiffness, percussion-induced rapid muscle contraction (PIRC), and percussion-induced muscle mounding (PIMM). RMD can be hereditary (hRMD) or immune-mediated (iRMD). hRMD is caused by pathogenic variants in caveolin-3 (CAV3) or caveolae-associated protein 1/ polymerase I and transcript release factor (CAVIN1/PTRF). CAV3 pathogenic variants are autosomal dominant or less frequently recessive while CAVIN1/PTRF pathogenic variants are autosomal recessive. CAV3-RMD manifests with a wide spectrum of clinical phenotypes, ranging from asymptomatic creatine kinase elevation to severe muscle weakness. Overlapping phenotypes are common. Muscle caveolin-3 immunoreactivity is often absent or diffusely reduced in CAV3-RMD. CAVIN1/PTRF-RMD is characterized by congenital generalized lipodystrophy (CGL, type 4) and often accompanied by several extra-skeletal muscle manifestations. Muscle cavin-1/PTRF immunoreactivity is absent or reduced while caveolin-3 immunoreactivity is reduced, often in a patchy way, in CAVIN1/PTRF-RMD. iRMD is often accompanied by other autoimmune disorders, including myasthenia gravis. Anti-cavin-4 antibodies are the serological marker while the mosaic expression of caveolin-3 and cavin-4 is the pathological feature of iRMD. Most patients with iRMD respond to immunotherapy. Rippling, PIRC, and PIMM are usually electrically silent. Different pathogenic mechanisms have been postulated to explain the disease mechanisms. In this article, we review the spectrum of hRMD and iRMD, including clinical phenotypes, electrophysiological characteristics, myopathological findings, and pathogenesis.
Journal of Neuro-Ophthalmology · 1995 · 4 citations
Intermittent Esotropia Associated with Rippling Muscle Disease
AbstractPURPOSE: We report a rare myopathy known as rippling muscle disease, with the unique feature of extraocular muscle involvement, presenting as a variable esotropia. METHODS: Chart review with a review of the literature. RESULTS: Neurologic and neuro-ophthalmic examinations as well as electromyography and muscle biopsy confirm that this case closely resembles those described in the literature with the additional feature of a variable esotropia. CONCLUSION: Rippling muscle disease may be associated with intermittent esotropia. The pathophysiology of this disorder is unknown, but the intermittent esotropia is likely related to "rippling" of the medial recti.
IntechOpen eBooks · 2023 · 0 citations · open access
The Potential Benefits of Drug-Repositioning in Muscular Dystrophies
AbstractMuscular dystrophies (MDs) are a complex group of rare neuromuscular disorders caused by genetic mutations that progressively weaken the muscles, resulting in an increasing level of disability. The underlying cause of these conditions consists of mutations in the genes in charge of a person’s muscle composition and functionality. MD has no cure, but medications and therapy can help control symptoms and slow the disease’s progression. Effective treatments have yet to be developed, despite the identification of the genetic origins and a thorough knowledge of the pathophysiological alterations that these illnesses induce. In this scenario, there is an urgent need for novel therapeutic options for these severe illnesses, and drug repositioning might be one feasible answer. In other words, drug repositioning/repurposing is an accelerated method of developing novel pharmaceuticals since the new indication is based on previously accessible safety, pharmacokinetic, and manufacturing data. This is particularly crucial for individuals with life-threatening illnesses such as MDs, who cannot wait for a conventional medication development cycle. This chapter aims to review the challenges and opportunities of drug-repositioning in a variety of MDs to establish novel treatment approaches for these incurable diseases.
Autoimmune Rippling Muscle Disease - Histologische Auffälligkeiten und Bindungsstudien
AbstractHintergrund: Rippling Muscle Disease (RMD) ist eine seltene Myopathie mit klinischen Zeichen erhöhter mechanischer Muskelerregbarkeit. Hierzu zählen Muskelwogen (Rippling), Wulstbildung der Muskulatur (Mounding) und Druck-induzierte rasche Muskelkontraktionen (PIRC). Bei den meisten RMD-Patienten lassen sich Mutationen im Caveolin-3-Gen (CAV3) auf Chromosom 3p25 nachweisen. In wenigen Fällen wurden erworbene Formen der RMD in Assoziation mit Autoimmunerkrankungen und Malignomen beschrieben.
Rhabdomyolyse – das Chamäleon auf der Intensivstation
AbstractMyotonia congenita Thomsen is a rare genetic disease caused by mutations in the skeletal muscle chloride channel gene (CLCN1). Although this channelopathy may cause disabling muscle symptoms, patient's daily routine can be almost inconspicuous. Nevertheless, during illness or acute diseases this neuromuscular disease may worsen and get clinically apparent up to severe rhabdomyolysis. Within this case report we describe and discuss the treatment of a patient with Myotonia congenita Thomsen treated at our hospital's intensive care unit. Rhabdomyolysis with acute renal failure and necessity of dialysis during the ICU stay was attributed to the initial reason for emergency hospitalization - an aortic dissection. Nevertheless, in this case the patient's myotonia caused rhabdomyolysis and initially led us on a wrong path. Diagnosis of the real cause of rhabdomyolysis is often difficult, although an early and adequate therapy may prevent complications. This case report demonstrates the importance of a thorough anamnesis with all aspects of the patient's history.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
