DeCure for Muscular dystrophy, limb-girdle, autosomal recessive 23
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for muscular dystrophy, limb-girdle, autosomal recessive 23 — screening already-approved drugs against its 4-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleMuscular dystrophy, limb-girdle, autosomal recessive 23 maps to a 4-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
Structures already discussed alongside muscular dystrophy, limb-girdle, autosomal recessive 23 in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Trypsin-modified Elongation Factor Tu — Tetracycline has a real, experimentally solved structure in complex with this target (PDB 2HCJ, 2.12 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
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RCSB Protein Data Bank · entry 2HCJ · 2.12 Å · ligand Tetracycline (TAC). Experimental structure, not a prediction.
What the evidence adds up to
A 1989 study of 470 families with Duchenne muscular dystrophy estimated that 6.8% of families with affected males actually had an autosomal recessive form, and that 2.5–4% of isolated male patients diagnosed with DMD might have the recessive form. That estimate was based on the number of families with at least one affected girl and the number of patients per sibship. The authors noted that this could explain inconsistent results between clinical diagnosis and dystrophin assessment.
A 2018 case report from Saudi Arabia described a patient with limb-girdle muscular dystrophy type 2B caused by a rare homozygous duplication c.164dupA in the DYSF gene. The authors stated that no curative treatment exists for dysferlinopathy, and that accurate diagnosis is important to avoid using steroids and immunosuppressive medications, which are not effective and may have side effects. A 2011 review listed 39 genes associated with limb-girdle muscular dystrophies and noted that only symptomatic treatments are available; potential therapies under study include stem-cell transplantation, exon skipping, gene delivery, RNAi, and gene editing.
A 2020 linkage study in one large autosomal dominant family localised the LGMD gene to chromosome 5q22.3-31.3 and excluded linkage to 15q, confirming genetic heterogeneity. A 2025 report described a young boy with autosomal recessive limb-girdle muscular dystrophy type 10 caused by a novel homozygous variant in the TTN gene, presenting with distal muscle weakness in all four limbs and thinning of legs, arms, and thighs. The prevalence of LGMD was given as 4–7 per 1000, with a spectrum of onset ages.
What is still missing are large, well-funded trials that can test the many proposed therapies — stem-cell transplantation, exon skipping, gene delivery, RNAi, and gene editing — in defined genetic subtypes. Patient stratification by specific gene mutation is needed, as is a trial design that can accommodate the rarity and heterogeneity of each recessive LGMD subtype. No drug has been shown in a controlled trial to alter the course of any autosomal recessive limb-girdle muscular dystrophy.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Annals of Neurology · 2008 · 77 citations · open access
Pathology is alleviated by doxycycline in a laminin‐α2–null model of congenital muscular dystrophy
AbstractOBJECTIVE: Congenital muscular dystrophy type 1A is an autosomal recessive disease that is caused by loss-of-function mutations in the laminin-alpha2 gene, and results in motor nerve and skeletal muscle dysfunction. In a previous study, we used genetic modifications to show that inappropriate induction of apoptosis was a significant contributor to pathogenesis in a laminin-alpha2-deficient mouse model of congenital muscular dystrophy type 1A. To identify a possible pharmacological therapy for laminin-alpha2 deficiency, we designed this study to determine whether treatment with minocycline or doxycycline, which are tetracycline derivatives reported to have antiapoptotic effects in mammals, would significantly increase lifespan and improve neuromuscular function in laminin-alpha2-deficient mice. METHODS: Mice that were homozygous for a targeted, inactivating mutation of the laminin-alpha2 gene were placed into control, minocycline-treated, or doxycycline-treated groups. Drug treatment began within 2 weeks of birth, and the progression of disease was followed over time using behavioral, growth, histological, and molecular assays. RESULTS: We found that treatment with either minocycline or doxycycline increased the median lifespan of laminin-alpha2-null mice from approximately 32 days to approximately 70 days. Furthermore, doxycycline improved postnatal growth rate and delayed the onset of hind-limb paralysis. Doxycycline-treated laminin-alpha2-deficient muscles had increased Akt phosphorylation, decreased inflammation, and decreased levels of Bax protein, terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling-positive myonuclei, and activated caspase-3. INTERPRETATION: Doxycycline or other drugs with similar functional profiles may be a possible route to improving neuromuscular dysfunction caused by laminin-alpha2-deficiency.
American Journal of Medical Genetics · 1989 · 45 citations
Estimate of the proportion of Duchenne muscular dystrophy with autosomal recessive inheritance
AbstractThe aim of the present report was to estimate the proportion of autosomal recessive (AR) inheritance among families with affected males diagnosed as Duchenne muscular dystrophy (DMD) in which X-linked inheritance could not be confirmed. A total of 470 families was studied: 20 with at least one affected girl with "Duchenne-like" phenotype and 450 with only affected boys. Based on the number of families with at least one affected girl and the number of patients per sibship among these pedigrees, the proportion of families with DMD inherited as an AR trait was estimated at 6.8%. It is also estimated that 2.5-4% of male isolated patients diagnosed as DMD may have the AR form, which could be one possible explanation for the inconsistent results between clinical diagnosis and dystrophin assessment in one case recently reported.
Journal of Back and Musculoskeletal Rehabilitation · 2018 · 9 citations
Limb-girdle muscular dystrophy type 2B: An unusual cause of proximal muscular weakness in Saudi Arabia
AbstractDysferlinopathies encompass a group of neuromuscular diseases characterized by the absence of dysferlin in skeletal muscle. It is a genetic disorder caused by a mutation in the dysferlin gene (DYSF) with an autosomal recessive mode of inheritance. In this article, we report a case of Limb-girdle muscular dystrophy type 2B with a rare homozygous duplication c.164dupA, p.(Ile57Hisfs*8) (rs863225020) in DYSF in a Saudi patient. To the best of our knowledge, this is the first case from Saudi Arabia with complete clinical data, pathology findings, radiology findings, and genetic analysis. Although there is no curative treatment for this disease, an accurate diagnosis is important to avoid using steroids and immunosuppressive medications, which are not effective and may have several side effects. Further studies are needed to explore potential therapies for this rare condition.
Neonatal rhabdomyolysis as a presentation of muscular dystrophy
AbstractWe report a unique presentation of X-linked recessive dystrophy as neonatal rhabdomyolysis. There was induration of the proximal musculature in an otherwise well neonate and striking CK elevation, without myoglobinuria. Muscle biopsy at age 1 year showed dystrophic alterations, and X chromosome analysis showed a deletion within or adjacent to the Duchenne/Becker locus.
Journal of Clinical Medicine · 2011 · 0 citations · open access
The Arkansas Leadership Academy Master Principal Program: Using Reflective Practice and Peer Learning Support Networks
AbstractLimb-girdle muscular dystrophies (LGMDs) are caused by mutations in multiple genes. This review article presents 39 genes associated with LGMDs. Some forms are inherited in a dominant fashion, while for others this occurs recessively. The classification of LGMDs has evolved through time. Lately, to be considered an LGMD, the mutation has to cause a predominant proximal muscle weakness and must be found in two or more unrelated families. This article also presents therapies for LGMDs, examining both available treatments and those in development. For now, only symptomatic treatments are available for patients. The goal is now to solve the problem at the root of LGMDs instead of treating each symptom individually. In the last decade, multiple other potential treatments were developed and studied, such as stem-cell transplantation, exon skipping, gene delivery, RNAi, and gene editing.
Confirmation of genetic heterogeneity in limb-girdle muscular dystrophy: Linkage of an autosomal dominant form to chromosome 5q
AbstractLimb-girdle muscular dystrophy (LGMD) is a clinically and genetically heterogeneous group of disorders, with both recessive and dominant forms reported. Recently, a series of recessive LGMD families were linked to chromosome 15q. We report herein the results of our linkage studies in a previously reported large autosomal dominant family. The LGMD gene in this family was localized to chromosome 5q22.3-31.3 by using a series of CA(n) microsatellite repeat markers. Linkage to 15q was excluded. These findings confirm genetic heterogeneity in this clinically diverse syndrome.
International Medical Case Reports Journal · 2025 · 0 citations · open access
Autosomal Recessive Limb-Girdle Muscular Dystrophy Type 10 (LGMD,10), Caused by a Novel Homozygous Variant in the TTN Gene
AbstractLimb-girdle muscular dystrophy was first introduced in the 1950s as a distinct family of unusual genetic diseases. The prevalence of the disease is about 4-7/1000, with a spectrum of onset at different ages. LGMD has a cluster of symptoms varying in severity and presentation in patients. Limb-girdle muscular dystrophy`s inheritance is unique as it can be autosomal dominant or recessive. We report a young boy with autosomal recessive limb-girdle muscular dystrophy (LGMD), presented with distal muscle weakness in all four limbs for three years and thinning of legs, arms, and thighs. Our gene of focus is TTN, which is associated with muscle elasticity and myogenesis. Our subtype reported is currently associated with a new homozygous TTN variant; thus, we are writing a novel variant mutation causing limb-girdle muscular dystrophy type 10.
Limb-Girdle Muscular Dystrophy Type 2B and Morbihan Disease: A Case Report With an Atypical Presentation
AbstractThis case report presents a 38-year-old man with no significant medical history who was referred to the Internal Medicine Department due to dermatosis and muscle weakness. A multidisciplinary diagnostic approach was initiated, including laboratory, imaging, and even histopathological studies. No definitive diagnosis was obtained. During the diagnostic process, the patient's clinical course was torturous, with evidence of increasing muscle weakness and inability to walk. Due to the lack of a definitive diagnosis, empirical treatment with systemic steroids was initiated, with no clinical evidence of improvement. After ruling out a neoplastic or autoimmune cause, a molecular panel for muscular dystrophies was performed, which identified NM_003494 (DYSF_v001): c.1382T>C; p.(Ile461Thr), a clinically pathogenic and heterozygous variant. This led to the diagnosis of limb-girdle muscle dystrophy type 2B with no evidence of association with dermatosis, consistent with Morbihan disease. Molecular diagnosis was crucial for an accurate diagnosis and thus enabled the implementation of therapeutic strategies aimed at improving the patient's quality of life. Muscular dystrophy type 2B is a disease that still lacks specific treatment and can progress to the point of disability. The patient was fully informed about the progression and prognosis of muscular dystrophy and was referred for physical rehabilitation with the goal of delaying permanent disability. Regarding Morbihan disease, the patient received the prescribed treatment for eight months, with notable improvement in edema and dermatological lesions.
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.
