DeCure for Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4 — 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 moduleMuscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4 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 muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 4 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
fukutin related protein (FKRP) — FKRP 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 cdpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6KAJ · 2.2249 Å · ligand CYTIDINE-5'-DIPHOSPHATE (CDP). Experimental structure, not a prediction.
What the evidence adds up to
Congenital muscular dystrophy-dystroglycanopathy type A, 4 (MDDGA4) is caused by mutations in the FKRP gene, leading to defective glycosylation of alpha-dystroglycan. A 2006 study of 13 patients with FKRP mutations found a wide spectrum of brain involvement. Five patients had normal intelligence and normal brain MRI. Three had isolated cerebellar cysts with mental retardation. The remaining five had cerebellar cysts plus structural brain changes ranging from focal periventricular nodular heterotopia to marked cerebellar dysplasia and pontine hypoplasia; one of these five had a phenotype resembling muscle-eye-brain disease and another had mild Walker-Warburg syndrome. The severity of central nervous system involvement broadly reflected the severity of disrupted alpha-dystroglycan glycosylation — expression was almost absent in the muscle-eye-brain-like cases and less severely reduced in those with the milder MDC1C phenotype.
A 2019 report followed two women with the Finnish variant of muscle-eye-brain disease (now MDDGA3, caused by POMGNT1 mutations) for almost 40 years. Their clinical picture remained quite stable since adolescence: severe intellectual and motor disability, extremely limited communication, visual impairment, epilepsy, joint contractures, repeated bowel obstructions, teeth abrasion from bruxism, irregular sleep, and previously unreported hypothermic periods manifesting as excessive sleepiness. Earlier literature describes the congenital muscular dystrophies as a heterogeneous group with weakness and dystrophic muscle biopsy present at birth or in the first months. A 2021 case report notes that muscle-eye-brain disease and Walker-Warburg syndrome are subtypes commonly associated with structural eye abnormalities alongside brain malformations. A 2013 review lists nine genes (FKTN, LARGE, FKRP, POMT1, POMT2, POMGnT1, DPM3, DPM2, WWP1, ISPD, and DAG1) in which mutations cause defective glycosylation of alpha-dystroglycan.
A 2001 review states there are still no curative treatment options for congenital muscular dystrophies; only regular follow-up and symptomatic care by a multidisciplinary team are available. No abstract in this set reports any drug trial or intervention that alters the course of the disease. What is missing is any funded clinical trial designed to test a specific compound in MDDGA4, any validated biomarker for stratifying patients by severity of brain involvement, and any natural history data that could power such a trial.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Archives of Neurology · 2006 · 104 citations · open access
Spectrum of Brain Changes in Patients With Congenital Muscular Dystrophy and FKRP Gene Mutations
AbstractOBJECTIVES: To report the spectrum of brain magnetic resonance imaging findings in 13 patients with congenital muscular dystrophy and FKRP gene mutations and to explore possible genotype-phenotype correlations. DESIGN: We retrospectively reviewed brain magnetic resonance imaging in patients with congenital muscular dystrophy and FKRP gene mutations. PATIENTS: Thirteen patients with congenital muscular dystrophy and mutations in the FKRP gene. RESULTS: Five of the 13 patients had the typical phenotype originally described for congenital muscular dystrophy (MDC1C) with normal intelligence and normal brain magnetic resonance imaging while 3 other patients had isolated cerebellar cysts and mental retardation without any other sign of posterior fossa of supratentorial abnormalities. In the remaining 5 patients cerebellar cysts were associated with structural brain changes involving the posterior fossa and the cortex, ranging from focal unilateral periventricular nodular heterotopia to marked cerebellar dysplasia and pontine hypoplasia. In 2 of these 5 patients the severity and distribution of changes resembled muscle-eye-brain disease in 1 patient who had mild Walker-Warburg syndrome. The distribution of FKRP gene mutations identified in this group of patients did not reveal any obvious association with the severity of central nervous system involvement. CONCLUSIONS: The severity of central nervous system involvement observed in our patients in contrast broadly reflected the severity of the disruption of alpha-dystroglycan glycosylation. In particular, dystroglycan expression was almost absent in the patients with muscle-eye-brain diseaselike phenotype and less severely reduced in the patients with congenital muscular dystrophy (MDC1C) with or without cerebellar cysts. This study further highlights the central role that dystroglycan has in neuronal migration.
Congenital Muscular Dystrophy with Eye and Brain Malformations in Six Dutch Patients*
AbstractFrom four Dutch families six patients, who have congenital muscular dystrophy, involvement of the central nervous system and of the eyes, or the so-called "muscle, eye and brain disease" (MEB-D), are reported. Two patients are still alive, in four autopsy could be performed. The clinical and morphological data of our patients are compared to those described in recent literature. The progression of the disease was rapid in five of our six patients. Our study supports the idea that within the MEB-D syndrome there are at least two different types of clinical expression, one with a rapid progression as described by Dobyns et al 1989 (9) and one with a slower progression as described in most patients of Santavuori et al 1989 (23). The study also confirms the autosomal recessive mode of inheritance of MEB-D.
American Journal of Medical Genetics Part A · 2019 · 4 citations
Two middle‐aged women with the Finnish variant of muscle‐eye‐brain disease (MEB)
AbstractMuscle-eye-brain disease (MEB) is a recessively inherited rare disease. Sixteen different gene mutations are known, with the most common mutations in the POMGNT1 gene. The disease is now called congenital muscular dystrophy-dystroglycanopathy type A3 (MDDGA3). It manifests itself as muscular dystrophy with eye and brain anomalies and intellectual disability. Previous clinical reports describe young patients. We have been able to follow two patients for almost 40 years. Their clinical picture has remained quite stable since adolescence, appearing as severe intellectual and motor disability, extremely limited communication skills, visual impairment, epilepsy, joint contractures, repeated bowel obstructions, teeth abrasion due to bruxism, an irregular sleep pattern and as a previously unreported feature hypothermic periods manifesting as excessive sleepiness.
Handbook of clinical neurology · 2001 · 0 citations
Towards a Flexible information Retrieval Approach based on the Context
AbstractThe congenital muscular dystrophies are a heterogeneous group of disorders in which weakness and dystrophic pattern on muscle biopsy are present at birth or during the first months of life. This chapter reviews the most common forms of congenital muscular dystrophies, including laminin α-2 (merosin) deficiency, Ullrich congenital muscular dystrophy, fukutin-related proteinopathy, rigid spine syndrome, and glycosylation disorders of α-dystroglycan. The latter group is often associated with neuronal migration defects including lissencephaly, pachygyria, cerebellar and brainstem abnormalities, and variable ocular anomalies. Typical clinical findings and underlying genetic defects are discussed to assist in the differential diagnosis and diagnostic work-up of patients with congenital muscular dystrophies. There are still no curative treatment options for patients with congenital muscular dystrophies but regular follow-up and symptomatic care by a multidisciplinary team considering the peculiarities of each disorder are important to maintain or improve patients' quality of life.
Indian Journal of Child Health · 2021 · 0 citations · open access
Muscle eye brain disease – A rare case of congenital muscular dystrophy
AbstractCongenital muscular dystrophies are a distinct group of inherited muscle disorders that manifest within the 1st year of life accompanied by weakness, hypotonia, and developmental delay. A distinguishing feature of congenital muscular dystrophy from other muscular dystrophies is an increased association with brain malformations, particularly disorders of cortical development such as lissencephaly, pachygyria, and polymicrogyria. Moreover, some subtypes of congenital muscular dystrophies (CMDs) such as muscle eye brain disease and Walker-Warburg syndrome are more commonly associated with structural eye abnormalities apart from brain malformations. The inheritance of CMD is usually autosomal recessive except for CMD with spinal rigidity and lamin A/C abnormality and Ullrich CMD.
Alpha-dystroglycanopathies: Clinical and genetic variability
AbstractAims: Alpha-dystroglycanopathies show a broad clinical spectrum from mild limb girdle to severe congenital muscular dystrophy with brain and eye abnormalities. Currently, mutations in nine genes are known which lead to defective glycosylation of α-dystroglycan: FKTN, LARGE, FKRP, POMT1, POMT2, POMGnT1, DPM3, DPM2, WWP1, ISPD or encodes α-dystroglycan, DAG1.
Science of Aging Knowledge Environment · 2002 · 0 citations
Other Noteworthy Papers This Week
AbstractD. E. Michele, R. Barresi, M. Kanagawa, F. Saito, R. D. Cohn, J. S. Satz, J. Dollar, I. Nishino, R. I. Kelley, H. Somer, V. Straub, K. D. Mathews, S. A. Moore, K. P. Campbell, Post-translational disruption of dystroglycan-ligand interactions in congenital muscular dystrophies. Nature 418 , 417-422 (2002). [Abstract] [Full Text] S. A. Moore, F. Saito, J. Chen, D. E. Michele, M. D. Henry, A. Messing, R. D. Cohn, S. E. Ross-Barta, S. Westra, R. A. Williamson, T. Hoshi, K. P. Campbell, Deletion of brain dystroglycan recapitulates aspects of congenital muscular dystrophy. Nature 418 , 422-425 (2002). [Abstract] [Full Text]
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.
