DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Proteus syndrome — screening already-approved drugs against its 4-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleProteus syndrome maps to a 4-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 proteus 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
AKT serine/threonine kinase 1 (AKT1) — AKT1 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 propanoylaminodrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7NH5 · 1.9 Å · ligand ~{N}-methyl-6-[4-[[4-[2-oxidanylidene-6-(propanoylamino)-3~{H}-benzimidazol-1-yl]piperidin-1-yl]methyl]phenyl]-5-phenyl-pyridine-3-carboxamide (UC8). Experimental structure, not a prediction.
What the evidence adds up to
In 2011, exome sequencing of biopsy samples from 29 patients with Proteus syndrome identified a somatic activating mutation (c.49G→A, p.Glu17Lys) in the oncogene AKT1 in 26 of those patients. The mutation was present in admixtures ranging from 1% to approximately 50% of alleles in affected tissues. Mutant cell lines showed greater AKT phosphorylation than control cell lines. This confirmed the hypothesis that the syndrome is caused by somatic mosaicism for a mutation that is lethal in the nonmosaic state, and it implicated activation of the PI3K-AKT pathway in the overgrowth and tumour susceptibility seen in the disorder. No other molecular cause has been reported in the literature summarised here.
Earlier clinical reports, from 1997 and 2010, described the range of manifestations in seven children and a 16-year-old female patient respectively: macrodactyly, vertebral abnormalities, asymmetric limb overgrowth, hyperostosis, abnormal fat distribution, asymmetric muscle development, connective tissue nevi, and vascular malformations. The 1997 report added new findings including blue sclerae, telecanthus, epiblepharon, endotropy, hemimegaly of the optic nerve, occipital dysmyelination, compression of the corpus callosum, craniosynostosis, decalcification and thinning of the cortical layer of long bones, and talipes equinus. A 2018 review noted that because symptoms and severity are unique to each patient, diagnosis and treatment are difficult, and argued for patient-centric drug delivery and the need for new drugs.
No clinical trial of any drug for Proteus syndrome is reported in these abstracts. There is no evidence of any treatment that alters the course of the disease. What is missing is a funded clinical trial, a validated outcome measure for a disorder with highly variable presentation, and a strategy for patient stratification that accounts for the low frequency of the mutation in affected tissues.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
New England Journal of Medicine · 2011 · 891 citations · open access
A Mosaic Activating Mutation in <i>AKT1</i> Associated with the Proteus Syndrome
AbstractBACKGROUND: The Proteus syndrome is characterized by the overgrowth of skin, connective tissue, brain, and other tissues. It has been hypothesized that the syndrome is caused by somatic mosaicism for a mutation that is lethal in the nonmosaic state. METHODS: We performed exome sequencing of DNA from biopsy samples obtained from patients with the Proteus syndrome and compared the resultant DNA sequences with those of unaffected tissues obtained from the same patients. We confirmed and extended an observed association, using a custom restriction-enzyme assay to analyze the DNA in 158 samples from 29 patients with the Proteus syndrome. We then assayed activation of the AKT protein in affected tissues, using phosphorylation-specific antibodies on Western blots. RESULTS: Of 29 patients with the Proteus syndrome, 26 had a somatic activating mutation (c.49G→A, p.Glu17Lys) in the oncogene AKT1, encoding the AKT1 kinase, an enzyme known to mediate processes such as cell proliferation and apoptosis. Tissues and cell lines from patients with the Proteus syndrome harbored admixtures of mutant alleles that ranged from 1% to approximately 50%. Mutant cell lines showed greater AKT phosphorylation than did control cell lines. A pair of single-cell clones that were established from the same starting culture and differed with respect to their mutation status had different levels of AKT phosphorylation. CONCLUSIONS: The Proteus syndrome is caused by a somatic activating mutation in AKT1, proving the hypothesis of somatic mosaicism and implicating activation of the PI3K-AKT pathway in the characteristic clinical findings of overgrowth and tumor susceptibility in this disorder. (Funded by the Intramural Research Program of the National Human Genome Research Institute.).
Pediatric Dermatology · 1997 · 24 citations · open access
Proteus Syndrome: New Findings in Seven Patients
AbstractSeven children with Proteus syndrome (PS) are reported. The majority of clinical findings coincide with what is reported in the literature. New findings were blue sclerae, telecanthus, epiblepharon, endotropy, hemimegaly of the optic nerve, occipital dysmyelination and compression of the corpus callosum, craneosynostosis, decalcification and thinning of the cortical layer of long bones, and talipes equinus. The clinical findings, possible etiology, differential diagnosis, and treatment of PS are discussed.
Dermatology Reports · 2010 · 1 citations · open access
Proteus syndrome: a case report and a case study review in China
AbstractProteus syndrome (PS) is a rare and sporadic disorder characterized by overgrowth of multiple tissues and a propensity to develop particular neoplasms. The clinical manifestations of PS include macrodactyly, vertebral abnormalities, asymmetric limb overgrowth and length discrepancy, hyperostosis, abnormal and asymmetric fat distribution, asymmetric muscle development, connective tissue nevi, and vascular malformations. We report a 16-year old female patient who manifested a number of these complications and review the Chinese literature about the diagnosis, natural history, and management of PS.
Asian Journal of Pharmaceutical and Clinical Research · 2018 · 0 citations · open access
PROTEUS SYNDROME: NEED FOR PATIENT CENTRIC THERAPY
AbstractProteus syndrome (PS) is a hamartomatous disorder with multisystem involvement that results from mutation in the AKT1gene. Since the symptoms and severity of PS are unique to each patient, diagnosis and treatment become hard for the physician. This article is concentrated upon the identification and recognition of specific characteristics of the disease, pathophysiology, symptoms, diagnosis, treatment and the necessity of advanced diagnosis, effective generalized and personalized therapy, as well as the requirement of new drugs for the management of PS. Detailed studies on the PS and evidence from the case reports revealed the requirement of intensive care, accurate diagnosis, and an effective treatment for each patient preferably patient-centric drug delivery due to the high degree of variation in the symptoms and clinical features among patients.
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.
