DeCure for Ullrich congenital muscular dystrophy 1C
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Ullrich congenital muscular dystrophy 1C — 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 moduleUllrich congenital muscular dystrophy 1C 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 ullrich congenital muscular dystrophy 1c 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 3 chain (COL6A3) — COL6A3 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 2009 natural history study of 13 Ullrich congenital muscular dystrophy patients followed from 1977 to 2007 at a London centre, mean symptom onset was 12 months. Eight patients (61.5%) walked independently at a mean age of 1.7 years, but nine (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 started noninvasive ventilation at a mean age of 14.3 years, and two died of respiratory insufficiency. The authors concluded that motor and respiratory decline is more rapid in the first decade and is invariable.
Four later reports identify specific COL6A1 or COL6A3 mutations in individual patients. A 2019 case describes a 2-year-old boy with two closely spaced de novo splice-site mutations in COL6A3 on the same allele, producing no normal mRNA. A 2018 report notes novel recessive COL6A1 mutations in a patient with the early-severe phenotype. A 2022 case of a 4-year-old Iranian boy with consanguineous parents found a novel homozygous COL6A1 deletion (c.2551_2562del) by whole exome sequencing, confirmed by Sanger sequencing. None of these genetic reports provide data on treatment or disease modification.
No drug or intervention is mentioned in any of these abstracts. What remains missing for Ullrich congenital muscular dystrophy 1C is any controlled trial of a pharmacological agent, any biomarker that predicts rate of decline, and any stratification of patients by mutation type or age at enrolment that might allow a trial to detect a treatment effect.
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.
Intractable & Rare Diseases Research · 2019 · 16 citations · open access
Management strategies in facioscapulohumeral muscular dystrophy
AbstractFacioscapulohumeral muscular dystrophy (FSHD) also known as Landouzy-Dejerine disease, is an autosomal-dominant disorder of the skeletal muscles with the name according to the various muscle groups it affects: the face, shoulders and upper arms. It is the third most common genetic degenerative disorder of the skeletal muscles without specific patterns in all the affected individuals. At present there is no cure for the disease but numerous management strategies are available to improve the quality of life and prevent further degeneration of various muscle groups. This review aims to provide an insight on the management strategies for FSHD patients including both lifestyle and medical intervention.
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.
Annals of Clinical Neurophysiology · 2018 · 0 citations · open access
Novel recessive mutations of <i>COL6A1</i> identified in the early severe phenotype of ullrich congenital muscular dystrophy
AbstractUllrich congenital muscular dystrophy (UCMD) is caused by mutations in one of three genes encoding collagen VI. Although UCMD usually shows an early onset, progressive weakness, contractures and hyperlaxity of the joints, and respiratory failure, it is well known to exhibit a wide spectrum of clinical severities. The severities of the phenotypic subtypes are mainly divided according to the ambulation status. We report a patient with the early-severe phenotype of UCMD who was diagnosed by the detection of novel recessive mutations in COL6A1.
Egyptian Journal of Medical Human Genetics · 2022 · 0 citations · open access
Exome sequencing identified a novel Col6α1 mutation in an Iranian patient with Ullrich congenital muscular dystrophy: a case report
AbstractAbstract Introduction Ullrich congenital muscular dystrophy (UCMD) is a severe form of inherited muscle weakness at birth. Recent genetic studies discovered that different gene mutations are responsible for UCMD clinical manifestation. Case report In this study, we carried out whole exome sequencing (WES) to recognize probable gene defects in an Iranian boy with UCMD. We found a novel disease-causing COL6α1 gene mutation (c.2551_2562del; p.Phe851_Arg854del), located in exon35 (NM_001848.3), causing a deletion mutation that has eliminated 12 bp. The WES-identified variant that was confirmed by Sanger sequencing for the patient and his consanguineous parents. Here, we report the clinical manifestations of 4-year-old Iranian patient who presented with muscle weakness since birth and proved compound homozygous mutation of the COL6A1 gene. Conclusion Our findings established that this detected COL6α1 mutation is the pathogenic variant for UCMD. This is the first genetic study indicating that c.2551_2562 mutation in homozygous state in COL6α1 gene is responsible for the UCMD phenotype.
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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