DeCure for Limb-girdle muscular dystrophy due to POMK deficiency
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for limb-girdle muscular dystrophy due to POMK deficiency — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleLimb-girdle muscular dystrophy due to POMK deficiency maps to a 1-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 limb-girdle muscular dystrophy due to pomk deficiency 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
The abstracts provided do not contain any study of drug repurposing for limb-girdle muscular dystrophy due to POMK deficiency. No abstract mentions POMK, and none tests a drug in patients with that specific genetic diagnosis. The 2021 case report of anti-HMGCR myopathy mimicking limb-girdle muscular dystrophy describes a 27-year-old man treated with prednisone, methotrexate, intravenous immunoglobulin, and rituximab. Muscle strength improved after a three-year delay, but creatine kinase levels remained above 1000 U/l. That patient did not have POMK deficiency; the myopathy was autoimmune and statin-unrelated.
The 2023 case series of five Latino patients with DOK7 mutation and limb-girdle weakness reports a novel mutation but no drug treatment. The 2012 and 2015 reviews cover Duchenne muscular dystrophy, not limb-girdle muscular dystrophy, and the 2001 review lists genetic forms without mentioning POMK. The 2021 review of discontinued Duchenne trials notes that 16 compounds failed despite early positive results, and only five of 40 compounds in development received conditional approval. None of those compounds is relevant to POMK deficiency.
What is missing: any clinical trial or preclinical study of a drug specifically for limb-girdle muscular dystrophy due to POMK deficiency. No patient stratification by POMK genotype has been attempted in a drug study. Funding for natural history studies and biomarker development in this ultra-rare form is absent from these abstracts. Without a trial designed for that mutation, no evidence exists for any drug in that population.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Gene and cell‐mediated therapies for muscular dystrophy
AbstractDuchenne muscular dystrophy (DMD) is a devastating muscle disorder that affects 1 in 3,500 boys. Despite years of research and considerable progress in understanding the molecular mechanism of the disease and advancement of therapeutic approaches, there is no cure for DMD. The current treatment options are limited to physiotherapy and corticosteroids, and although they provide a substantial improvement in affected children, they only slow the course of the disorder. On a more optimistic note, more recent approaches either significantly alleviate or eliminate muscular dystrophy in murine and canine models of DMD and importantly, many of them are being tested in early phase human clinical trials. This review summarizes advancements that have been made in viral and nonviral gene therapy as well as stem cell therapy for DMD with a focus on the replacement and repair of the affected dystrophin gene.
Current Opinion in Neurology · 2001 · 22 citations
The ABCʼs of limb-girdle muscular dystrophy: α-sarcoglycanopathy, Bethlem myopathy, calpainopathy and more
AbstractLimb-girdle muscular dystrophy is a class of disorders encompassing many forms of this disease. Variation exists between the inheritance patterns, genes responsible, course of disease and symptoms, with the cohesive factor among these disorders being the predominance of proximal muscle weakness. Here we review each form of limb-girdle muscular dystrophy with attention to molecular genetics, clinical features, inheritance, and diagnostic issues pertaining to each primary genetic cause.
European Journal of Case Reports in Internal Medicine · 2021 · 3 citations · open access
Chronic Onset Form of Anti-HMG-CoA Reductase Myopathy
AbstractWe report a case of anti-HMGCR myopathy mimicking limb-girdle muscular dystrophy in a 27-year-old male patient with no history of statin intake and presenting with a chronic onset form over 3 years. Treatment with prednisone and methotrexate was initiated with an insufficient response, so intravenous immunoglobulin was added. One year after initial treatment was started, as levels of creatine kinase (CK) were >1000 U/l, treatment with rituximab was added. Despite a 3-year delay before treatment, muscle strength improved even though CK levels remain elevated. LEARNING POINTS: We describe a case of anti-HMGCR myopathy mimicking limb-girdle muscular dystrophy, which resulted in delayed diagnosis and management.The patient's muscular strength improved but creatine kinase levels remain elevated despite comprehensive treatment.
Oxford University Press eBooks · 2015 · 1 citations
Biochemistry of Duchenne muscular dystrophy
AbstractAbstract The literature on the biochemistry of muscular dystrophy is overwhelming. It could be argued that, now that the primary defect has been identified in DMD and shown to be a deficiency of muscle dystrophin, it is irrelevant to approach an understanding of the pathogenesis through the findings of conventional biochemistry. The authors feel that molecular and biochemical studies could complement each other. What has been learned so far concerning biochemical changes in dystrophic muscle and how these relate to the deficiency of dystrophin will doubtless fill in details of how the disease process starts and progresses, and why it affects some muscles more than others. It is also conceivable that the more we know of the detailed pathogenesis of DMD, the more we may understand these processes in other muscular dystrophies. With such details, it may be possible to better consider a rational approach to any drug therapy.
INDIGO (University of Illinois at Chicago) · 2021 · 0 citations · open access
Presentation1_Lessons Learned from Discontinued Clinical Developments in Duchenne Muscular Dystrophy.pdf
Abstract<p>Duchenne muscular dystrophy (DMD) is an X-linked condition caused by a deficiency of functional dystrophin protein. Patients experience progressive muscle weakness, cardiomyopathy and have a decreased life expectancy. Standards of care, including treatment with steroids, and multidisciplinary approaches have extended the life expectancy and improved the quality of life of patients. In the last 30 years, several compounds have been assessed in preclinical and clinical studies for their ability to restore functional dystrophin levels or to modify pathways involved in DMD pathophysiology. However, there is still an unmet need with regards to a disease-modifying treatment for DMD and the attrition rate between early-phase and late-phase clinical development remains high. Currently, there are 40 compounds in clinical development for DMD, including gene therapy and antisense oligonucleotides for exon skipping. Only five of them have received conditional approval in one jurisdiction subject to further proof of efficacy. In this review, we present data of another 16 compounds that failed to complete clinical development, despite positive results in early phases of development in some cases. We examine the reasons for the high attrition rate and we suggest solutions to avoid similar mistakes in the future.</p>
A novel DOK7 mutation causing limb-girdle congenital myasthenic syndrome
AbstractWe report a case series of 5 Latino patients with limb-girdle pattern weakness, four patients are sisters, with one patient unrelated. Repetitive nerve stimulation showed a significant decrement in all cases. Targeted genetic testing for congenital myasthenic syndromes demonstrated a known DOK7 pathogenic mutation in each case, and in all five cases also revealed a novel DOK7 missense mutation in exon 7 with c.94G>A; providing strong evidence this mutation is pathogenic. DOK7-related congenital myasthenic syndrome often lacks oculobulbar involvement, and may present with limb-girdle weakness, mimicking limb-girdle muscular dystrophy.
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.
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