DeCure for Ullrich congenital muscular dystrophy 1A
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Ullrich congenital muscular dystrophy 1A — 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 1A 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 1a 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
Ullrich congenital muscular dystrophy is caused by mutations in COL6A1, COL6A2, or COL6A3. A 2019 report described a 2-year-old boy with two closely spaced de novo splice-site mutations in cis on COL6A3 (c.6283-1 G>G/T and c.6310-2 A>A/T); neither parent carried the mutations, and normal mRNA was still produced. A 2022 case identified a novel homozygous deletion in COL6A1 (c.2551_2562del; p.Phe851_Arg854del) in a 4-year-old Iranian boy with consanguineous parents. A 2024 study of two unrelated Yakut families found compound heterozygous mutations in COL6A2 (c.1561C>T and c.2329T>C) in one family and a homozygous c.2329T>C mutation in the other; all showed muscle weakness, hypotonia, joint hypermobility, contractures, delayed motor development, spinal deformity, and skin changes. A 2018 report described novel recessive COL6A1 mutations in a patient with the early-severe phenotype, defined by ambulation status.
No drug repurposing data specific to Ullrich congenital muscular dystrophy were reported in these abstracts. A 2023 review discussed drug repositioning as a potential accelerated strategy for muscular dystrophies generally, noting that no cure exists and that current treatments only control symptoms and slow progression. The review did not name any specific repurposed drug or provide clinical trial results for any muscular dystrophy subtype.
The abstracts provide no survival or response rates, no sample sizes beyond single patients or two families, and no evidence that any drug has been tested in Ullrich congenital muscular dystrophy. What is missing is any clinical trial testing a repurposed drug in this specific disease, funding for such trials, and a clear patient stratification strategy given the wide clinical severity spectrum and the variety of COL6A1, COL6A2, and COL6A3 mutations.
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.
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.
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.
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.
Yakut Medical Journal · 2024 · 0 citations · open access
Ullrich congenital muscular dystrophy: clinical case study
AbstractIntroduction. Ullrich congenital muscular dystrophy (Ullrich СMD, OMIM #254090) is the most severe form of skeletal muscle collagenopathy associated with three genes (COL6A1, COL6A2, COL6A3). The purpose of the report was to present our own observation of clinical cases with Ullrich congenital muscular dystrophy in two unrelated Yakut families. Materials and methods. A clinical and genealogical examination, electroneuromyography, muscle MRI, muscle biopsy, and molecular genetic research using the massively parallel sequencing method were carried out. Results. The cause of the disease in the first family was two mutations in a compound heterozygous state: c.1561C>T and c.2329T>C in the COL6A2 gene; in the second family, the c.2329T>C mutation in the COL6A2 gene in a homozygous state. The clinical picture of the disease was manifested by muscle weakness and hypotonia, hypermobility of the interphalangeal joints, contractures of the elbow, ankle and knee joints, delayed motor development, spinal deformity, and skin changes. The type of inheritance in families is autosomal recessive. Conclusions. Despite the rarity of the disease, neurologists and geneticists, when identifying symptoms of myopathy, delayed motor development, and the presence of hypermobility in the distal joints, contrasting with retractions of the proximal and axial joints, must be alert to Ullrich CMD. Next-generation sequencing techniques make it easier to diagnose the disease. Keywords: congenital muscular dystrophy, Ullrich's disease, COL6A2, Yakut family, clinical case.
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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