DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Ullrich congenital muscular dystrophy — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleUllrich congenital muscular dystrophy maps to a 3-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 ullrich congenital 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
collagen type VI alpha 1 chain (COL6A1) — COL6A1 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 9GTU · 3.14 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
In a natural history study of 13 Ullrich congenital muscular dystrophy patients aged 15 or older at last visit, mean symptom onset was 12 months. Eight patients (61.5%) walked independently at a mean age of 1.7 years. Nine patients (69.2%) became constant wheelchair users at a mean age of 11.1 years. Forced vital capacity was abnormal in all patients from age 6 years, declining at a mean rate of 2.6% yearly. Nine patients (69.2%) started noninvasive ventilation at a mean age of 14.3 years. Two patients died of respiratory insufficiency. The authors state that motor and respiratory decline is more rapid in the first decade and that deterioration is invariable.
A 2019 case report describes a 2-year-old boy diagnosed with Ullrich congenital muscular dystrophy by muscle biopsy. COL6A3 gene analysis found two heterozygous splice-site mutations located on the same allele, both de novo, with no mutation detected in either parent. Normal mRNA was still produced.
A 2023 review of drug repositioning in muscular dystrophies notes that no cure exists for these disorders and that effective treatments have yet to be developed despite knowledge of genetic causes and pathophysiology. The review presents drug repurposing as a potential accelerated development strategy because safety and pharmacokinetic data already exist, but it does not report any specific repurposed drug tested in Ullrich congenital muscular dystrophy patients.
What is missing is any clinical trial testing a repurposed drug specifically in Ullrich congenital muscular dystrophy, funding for such a trial, and a clear patient stratification strategy given the variable natural history described in the 13-patient cohort.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Neurology · 2009 · 158 citations
Natural history of Ullrich congenital muscular dystrophy
AbstractOBJECTIVE: To describe the course, complications, and prognosis of Ullrich congenital muscular dystrophy (UCMD), with special reference to life-changing events, including loss of ambulation, respiratory insufficiency, and death. METHODS: Review of the case notes of 13 patients with UCMD, aged 15 years or older at last visit, followed up at a tertiary neuromuscular centre, London, UK, from 1977 to 2007. Data collected were age at onset of symptoms, presenting symptoms, mobility, contractures, scoliosis, skin abnormalities, respiratory function, and feeding difficulties. RESULTS: The mean age at onset of symptoms was 12 months (SD 14 months). Eight patients (61.5%) acquired independent ambulation at a mean age of 1.7 years (SD 0.8 years). Nine patients (69.2%) became constant wheelchair users at a mean age of 11.1 years (SD 4.8 years). Three patients continued to ambulate indoors with assistance. Forced vital capacity (FVC) values were abnormal in all patients from age 6 years. The mean FVC (% predicted) declined at a mean rate of 2.6% (SD 4.1%) yearly. Nine patients (69.2%) started noninvasive ventilation at a mean age of 14.3 years (SD 5.0 years). Two patients died of respiratory insufficiency. CONCLUSION: In Ullrich congenital muscular dystrophy (UCMD), the decline in motor and respiratory functions is more rapid in the first decade of life. The deterioration is invariable, but not always correlated with age or severity at presentation. This information should be of help to better anticipate the difficulties encountered by patients with UCMD and in planning future therapeutic trials in this condition.
Human Genome Variation · 2019 · 5 citations · open access
Two closely spaced mutations in cis result in Ullrich congenital muscular dystrophy
AbstractA 2-year-old boy was diagnosed with Ullrich congenital muscular dystrophy (UCMD) by muscle biopsy. COL6A3 gene analysis by next-generation sequencing revealed two heterozygous splice-site mutations (c.6283-1 G > G/T and c.6310-2 A > A/T), whereas normal mRNA was produced. Genomic DNA analysis revealed two mutations located on the same allele; however, no mutation was detected in either parent. These results indicated that two closely spaced de novo mutations resulted in the autosomal dominant UCMD.
AbstractOBJECTIVES: To describe genetic and clinical features of Ullrich congenital muscular dystrophy (UCMD), and to report the case of a patient diagnosed with UCMD after an exhaustive investigation, which included collagen VI immunohistochemical and genomic analyses. DESCRIPTION: This study was based on clinical, immunohistochemical assessment of muscle tissue and genomic analysis of dermal fibroblasts of a 7 1/2-year old boy and of the DNA of his parents. Clinical aspects and differential diagnosis with other disorders are discussed. COMMENTS: A better knowledge of congenital muscular dystrophies will improve the number of correct diagnoses and open new horizons for the treatment of such diseases. Genetic evaluation of UCMD patients has relevant implications for prognosis and genetic counseling of the family. The dissemination of this disorder in the pediatric community is advisable, because of the early onset of clinical manifestations and the fact that it is frequently misdiagnosed or not diagnosed at all.
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.
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.
