DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for tibial muscular dystrophy — 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 moduleTibial muscular dystrophy 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 tibial muscular dystrophy 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.
Molecular view
LDL receptor related protein 4 (LRP4) — LRP4 is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8S9P · 3.8 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
The 2009 study tested TAT-utrophin protein replacement in mdx mice, a model of Duchenne muscular dystrophy, not tibial muscular dystrophy. Injected TAT-micro-utrophin reduced serum creatine kinase from 11,290 U/L to 5,950 U/L, reduced centrally nucleated fibres from 54% to 37%, reduced eccentric contraction force drop from 72% to 40%, and increased specific force from 9.7 N/cm² to 12.8 N/cm². The authors called this the first evidence for TAT-utrophin as a protein-replacement therapy for muscle diseases caused by dystrophin loss. No data on tibial muscular dystrophy were provided.
A 2013 survey of 170 people with myotonic and facioscapulohumeral muscular dystrophy found that fatigue (91%), imbalance (82%), and pain (77%) were the most common symptoms. Fatigue severity averaged 5.14 on a 0–10 scale, imbalance 4.95. Symptoms were associated with 10–17% of variance in mental health, home competency, social integration, and productive activity. The survey did not include tibial muscular dystrophy patients.
A 2021 review stated that more than 30 years after the first protein identification in a muscular dystrophy, there is still no effective treatment. It described experimental animal models and gene therapy approaches aimed at restoring dystrophin or compensating for its deficiency. The review did not mention tibial muscular dystrophy specifically.
No abstract addressed tibial muscular dystrophy directly. The 1965 abstract about electric breakdown in glass in caesium vapour is unrelated. What is missing for tibial muscular dystrophy specifically: any clinical trial data, any drug tested in that patient population, any animal model of the disease, and any symptom survey that includes those patients. The evidence base for drug repurposing in tibial muscular dystrophy is absent.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
PLoS Medicine · 2009 · 89 citations · open access
Functional Substitution by TAT-Utrophin in Dystrophin-Deficient Mice
AbstractBACKGROUND: The loss of dystrophin compromises muscle cell membrane stability and causes Duchenne muscular dystrophy and/or various forms of cardiomyopathy. Increased expression of the dystrophin homolog utrophin by gene delivery or pharmacologic up-regulation has been demonstrated to restore membrane integrity and improve the phenotype in the dystrophin-deficient mdx mouse. However, the lack of a viable therapy in humans predicates the need to explore alternative methods to combat dystrophin deficiency. We investigated whether systemic administration of recombinant full-length utrophin (Utr) or DeltaR4-21 "micro" utrophin (muUtr) protein modified with the cell-penetrating TAT protein transduction domain could attenuate the phenotype of mdx mice. METHODS AND FINDINGS: Recombinant TAT-Utr and TAT-muUtr proteins were expressed using the baculovirus system and purified using FLAG-affinity chromatography. Age-matched mdx mice received six twice-weekly intraperitoneal injections of either recombinant protein or PBS. Three days after the final injection, mice were analyzed for several phenotypic parameters of dystrophin deficiency. Injected TAT-muUtr transduced all tissues examined, integrated with members of the dystrophin complex, reduced serum levels of creatine kinase (11,290+/-920 U versus 5,950+/-1,120 U; PBS versus TAT), the prevalence of muscle degeneration/regeneration (54%+/-5% versus 37%+/-4% of centrally nucleated fibers; PBS versus TAT), the susceptibility to eccentric contraction-induced force drop (72%+/-5% versus 40%+/-8% drop; PBS versus TAT), and increased specific force production (9.7+/-1.1 N/cm(2) versus 12.8+/-0.9 N/cm(2); PBS versus TAT). CONCLUSIONS: These results are, to our knowledge, the first to establish the efficacy and feasibility of TAT-utrophin-based constructs as a novel direct protein-replacement therapy for the treatment of skeletal and cardiac muscle diseases caused by loss of dystrophin.
American Journal of Physical Medicine & Rehabilitation · 2013 · 25 citations
Symptom Burden in Persons with Myotonic and Facioscapulohumeral Muscular Dystrophy
AbstractOBJECTIVE: This study examines the prevalence of pain, fatigue, imbalance, memory impairment, and vision loss in persons with myotonic and facioscapulohumeral dystrophy and their association with functioning. DESIGN: A survey (N = 170) included measures of severity (0-10 scales) and course of these symptoms as well as measures of social integration, home competency, mental health, and productive activity. Descriptive and regression analyses examined the associations between symptoms and functioning. RESULTS: Fatigue (91%), imbalance (82%), and pain (77%) were the most commonly reported. The most severe symptom was fatigue (mean ± SD severity, 5.14 ± 2.81), followed by imbalance (4.95 ± 3.25). Symptoms were most likely to stay the same or worsen since onset. Controlling for potential medical and demographic confounds, symptoms were associated with 17% of the mental health variance, 10% of home competency, 10% of social integration, 16% of productive activity for myotonic dystrophy type 1, and 12% of productive activity for facioscapulohumeral muscular dystrophy. CONCLUSIONS: Pain, fatigue, and imbalance are common in persons with muscular dystrophy. Interventions may be useful to mitigate their impact on functioning. Further research should examine these relationships to guide clinical practices.
Experimental and Therapeutic Medicine · 2021 · 14 citations · open access
Muscular dystrophy: Experimental animal models and therapeutic approaches (Review)
AbstractThe muscular dystrophies are a heterogeneous group of genetically inherited diseases characterized by muscle weakness and progressive wasting, which can cause premature death in severe forms. Although >30 years have passed since the identification of the first protein involved in a type of muscular dystrophy, there is no effective treatment for these disabling disorders. In the last decade, several novel therapeutic approaches have been developed and investigated as promising therapeutic approaches aimed to ameliorate the dystrophic phenotype either by restoring dystrophin expression or by compensating for dystrophin deficiency. Concurrently, with the development of therapeutic approaches, in addition to naturally occurring animal models, a wide range of genetically engineered animal models has been generated. The use of animals as models of muscular dystrophies has greatly improved the understanding of the pathogenicity of these diseases and has proven useful in gene therapy studies. In this review, we summarize these latest innovative therapeutic approaches to muscular dystrophies and the usefulness of the various most common experimental animal models.
ELECTRIC BREAKDOWN THROUGH A SLOT IN GLASS IN A CESIUM VAPOR ATMOSPHERE
AbstractThe muscular dystrophies are a heterogeneous group of genetically inherited diseases characterized by muscle weakness and progressive wasting, which can cause premature death in severe forms. Although >30 years have passed since the identification of the first protein involved in a type of muscular dystrophy, there is no effective treatment for these disabling disorders. In the last decade, several novel therapeutic approaches have been developed and investigated as promising therapeutic approaches aimed to ameliorate the dystrophic phenotype either by restoring dystrophin expression or by compensating for dystrophin deficiency. Concurrently, with the development of therapeutic approaches, in addition to naturally occurring animal models, a wide range of genetically engineered animal models has been generated. The use of animals as models of muscular dystrophies has greatly improved the understanding of the pathogenicity of these diseases and has proven useful in gene therapy studies. In this review, we summarize these latest innovative therapeutic approaches to muscular dystrophies and the usefulness of the various most common experimental animal models.
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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