DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for McCune-Albright syndrome — 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 moduleMcCune-Albright syndrome 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 mccune-albright syndrome 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
GNAS complex locus (GNAS) — GNAS 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 oladrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8WW2 · 2.79 Å · ligand OLEIC ACID (OLA). Experimental structure, not a prediction.
What the evidence adds up to
McCune-Albright syndrome is a rare disease caused by an activating mutation in the gene for the G protein subunit GSα, which stimulates cellular cyclic AMP formation. The mutation occurs early during embryogenesis and results in a variable constellation of abnormalities involving bone, skin, endocrine glands, and other tissues. The syndrome is classically defined by the clinical triad of fibrous dysplasia of bone, café-au-lait macules, and endocrinopathies. In females it frequently manifests as precocious puberty. The partial or atypical form usually presents with only one or two cardinal characteristics because the distribution of GNAS gene mutations is often restricted to affected tissues.
In a 2017 series of eleven patients, the diagnosis and clinical course were described. A 2022 case report of a 15-year-old male noted that McCune-Albright syndrome remains a diagnostic challenge and that delayed diagnosis may have significant consequences. A 2022 case of a 14-year-old girl presenting with left otalgia and recurrent otitis found café-au-lait macules, slight left exophthalmos, narrowing of the external auditory canal, and conductive hearing loss with a 35 dB air-bone gap. A CT scan showed a large "ground glass" appearance of the left temporal region. In 90% of cases, fibrous dysplasia manifests as a disorder of the craniofacial skeleton, affecting the maxilla, mandible, and even the temporal bone.
Treatment is directed toward the specific symptoms apparent in each individual and is palliative. A 2024 case report of a 6-year-old girl described treatment as palliative, with surgery planned for bilateral femur fractures and a rehabilitation program. Management of endocrinopathies is usually medical; precocious puberty in girls is most often treated with aromatase inhibitors. Management of craniofacial fibrous dysplasia aims to correct functional and aesthetic damage. Rehabilitation programs are reported to provide significant improvement in quality of life.
A 2014 laboratory study identified three sites in the Gs alpha protein — F142, R231, and L266 — that, when mutated, suppressed the constitutive activity caused by the R201H mutation. Both F142S and R231C were able to suppress the constitutive activity of the R201C and R201S substitutions. L266N suppressed R201S. However, these suppressor mutations were unable to suppress the constitutive activity of the Q227L substitution, which is associated with a variety of adenomas, suggesting the action is specific to the R201 site and not generalizable. What is still missing is any clinical application of these laboratory findings, as no trials in patients have been reported. The rarity of the disease makes patient stratification and trial design difficult, and funding for such work remains limited.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Current Opinion in Endocrinology & Diabetes · 1999 · 46 citations
McCune-Albright syndrome: new insights
AbstractMcCune-Albright syndrome is a rare disease caused by an activating mutation in the gene for the G protein subunit (GSα) that stimulates cellular cyclic AMP formation. The mutation occurs early during embryogenesis and results in a variable constellation of abnormalities involving bone, skin, endocrine glands, and other tissues. Although traditionally regarded as a disease of children, clinical manifestations may progress into adulthood. Efforts are being made to define the precise mechanisms by which inappropriate GSα activation affects cellular proliferation and differentiated function and to develop more effective means to treat fibrous dysplasia of bone.
McCune–Albright Syndrome: Diagnosis and clinical course in eleven patients
AbstractMcCune–Albright Syndrome (MAS) (OMIM #174800) is a rare and complex genetic disorder. It is characterized by bone lesions that mainly present as polyostotic fibrous dysplasia (PFD), “café-au-lait” spots (CALS), and the autonomous hyperfunction of various endocrine organs; it frequently manifests in females as precocious puberty.1 However, the partial or atypical form of MAS usually presents with only one or two cardinal characteristics given that the distribution of GNAS gene (locus 20q13.2, #139320) mutations are often restricted to affected tissues.
Turkish Journal of Physical Medicine and Rehabilitation · 2022 · 2 citations · open access
Fibrous dysplasia and McCune-Albright syndrome: A case report with review of literature on the rehabilitation approach
AbstractMcCune-Albright syndrome is classically defined by the clinical triad of fibrous dysplasia (FD) of the bone, café-au-lait macules, and endocrinopathies. We report the case of a 15-year-old male with a diagnosed with McCune Albright syndrome. McCune-Albright syndrome remains a diagnostic challenge, and delayed diagnosis may have significant consequences. Routine musculoskeletal screening along with other endocrinopathies should be kept in mind. The rehabilitation programs that provides significant improvement in their quality of life. The treatment of McCune-Albright syndrome is directed toward the specific symptoms that are apparent in each individual.
Pharmacognosy Journal · 2024 · 1 citations · open access
A Girl with McCune-Albright Syndrome: Case Study
AbstractMcCune-Albright syndrome (MAS) is a rare genetic disease characterized by skeletal, cutaneous, and endocrine system involvement. We report a 6-year-old girl with fibrous dysplasia, café-au-lait macula, and multiple hyperfunctional endocrinopathies. Treatment was palliative, the patient was planned for surgery on bilateral femur fractures and a rehabilitation program.
Annals of Medicine and Surgery · 2022 · 0 citations · open access
Otalgia revealing McCune-Albright syndrome: A case report
AbstractIntroduction and importance: McCune-Albright syndrome (MAS) is typically described by the asociation of cutaneous (coffee-at-milk spots), endocrine (endocrine hyperfunction most often precocious puberty), and fibrous dysplasia (FD). In 90% of cases, AD manifests itself as a disorder of the craniofacial skeleton, affecting the maxilla, mandible, and even the temporal bone. Case presentation: We report the case of a 14-year-old girl who presented with complaints of left otalgia with the notion of recurrent otitis evolving for one year, she presents as antecedent an early puberty. At the examination, we found café-au-lait macules, and a slight left exophthalmos without visual acuity decrease. Otoscopic examination showed a narrowing of the external auditory canal (EAC). An audiogram showed conductive hearing loss in the left ear; the air-bone gap was 35 dB. A computed tomography (CT) scan was performed, showing a large "ground glass" appearance of the left temporal region. Given the presence of the cafe-au-lait spot, fibrous dysplasia of the temporal bone, and a history of early puberty, the diagnosis of McCune-Albright syndrome was made. clinical Discussion: Management of SMA is based on the needs of the individual patient and should be performed by a multidisciplinary team. Management of endocrinopathies is usually medical, with precocious puberty in girls most often treated with aromatase inhibitors. The objectives of the management of craniofacial DF are to correct the functional and aesthetic damage. Conclusion: McCune-Albright syndrome (MAS) is a rare disease. The involvement of the craniofacial region by FD during SAM is a complicated entity, in its effects and in its management.
Intragenic suppressors of McCune‐Albright syndrome R201H mutations also suppress other constitutively active Gs alleles (843.5)
AbstractMcCune‐Albright Syndrome (MAS) is a genetic disorder caused by a mutation in Gs alpha at Arg201 that inhibits GTP hydrolysis, constitutively activating the protein. We identified three sites that, when mutated, suppressed the constitutive activity caused by R201H: F142, R231, and L266. None of the three mutations by themselves caused constitutive activity of the protein or significantly changed cellular responsiveness to hormone, as measured by the ability of a luteinizing hormone receptor agonist to activate cAMP production. We have now examined the ability of mutations at these three sites to suppress other activating mutations of Gs alpha. Other McCune‐Albright associated mutations include R201C and R201S. Both F142S and R231C were able to suppress the constitutive activity of both of previously untested R201 substitutions. L266N was able to suppress R201S, and experiments investigating its effects on R201C are ongoing. Gs alpha can also be constitutively activated by the Q227L substitution, associated with a variety of adenomas. The mutations identified as suppressors of R201H were all unable to suppress the constitutive activity of Q227L, suggesting that the action of the suppressors is specific to the R201 site and not generalizable to other activating perturbations of Gs alpha. Grant Funding Source : Supported by NIH grant 1R15ED020190‐01
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.
