DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for autosomal recessive osteopetrosis 1 — 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 moduleAutosomal recessive osteopetrosis 1 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 autosomal recessive osteopetrosis 1 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
pleckstrin homology and RUN domain containing M1 (PLEKHM1) — PLEKHM1 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 gtpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8JC5 · 2.01 Å · ligand GUANOSINE-5'-TRIPHOSPHATE (GTP). Experimental structure, not a prediction.
What the evidence adds up to
The first abstract describes a single asymptomatic 14-year-old girl with autosomal dominant type II osteopetrosis, not the autosomal recessive form. No treatment or outcome data are reported.
The 2018 abstract reports whole exome sequencing in a cohort of osteopetrosis patients. Among autosomal recessive osteopetrosis patients, TCIRG1 was confirmed as the most frequently mutated gene. Mutations were also found in FERMT3 and USB1, genes very rarely associated with the disease. Four deep intronic mutations in TCIRG1 and two synonymous changes in TCIRG1 and CLCN7 were shown to be causative. No clinical outcomes, survival, or response rates are given.
The 2020 abstract states that autosomal recessive osteopetrosis is caused by mutations in at least eight genes related to osteoclast function. It describes the condition as characterised by failure of osteoclasts to resorb bone, impaired bone modelling and remodelling, skeletal fragility despite increased bone mass, hematopoietic insufficiency, hypocalcaemia, disturbed tooth eruption, nerve entrapment syndromes, and growth impairment. Some cases involve progressive neurological deterioration. No treatment, trial, or survival data are provided.
No drug is mentioned in any of these abstracts. What is missing for autosomal recessive osteopetrosis is any controlled trial of a therapy, any prospective data on disease-modifying interventions, and any stratification of patients by genotype or neurological involvement.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
TAJ Journal of Teachers Association · 2009 · 0 citations · open access
Autosomal Dominant Type II Osteopctrosis in an Asymptomatic Adolescent: A Case Report
AbstractOsteopetrosis is a heterogeneous group of heritable conditions in which there is a defect in bone resorption by osteoclasts. The disease has variable mode of inheritance with variable expression of severity. We are reporting a 14 year old asymptomatic girl with autosomal dominant type II osteopetrosis and then the literature is reviewed.TAJ 2009; 22(1): 251-254
Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) · 2018 · 0 citations · open access
NEW INSIGHTS IN BONE BIOLOGY FROM EXOME SEQUENCING OF RARE SKELETAL DISEASES
AbstractWhole exome sequencing (WES) is a powerful tool to identify new molecules involved in skeletal homeostasis. In particular we used WES to establish the molecular diagnosis of two particular skeletal diseases: osteopetrosis and the acrofrontofacionasal dysostosis 1 (AFFND1). The osteopetroses are a group of rare bone diseases characterized by increased bone density due to the failure in bone resorption. Due to their genetic heterogeneity, WES represents a valuable strategy to identify the genetic defect. We analyzed osteopetrotic patients with autosomal dominant osteopetrosis (ADO) and autosomal recessive osteopetrosis (ARO), which is the most severe form. In our cohort we performed molecular diagnosis of 4 ADOI or ADOII patients that carried mutations in the LRP5 and CLCN7 genes, respectively. The analysis of ARO patients confirmed TCIRG1 as the most frequently mutated gene, identified mutations in the other known ARO genes and in genes very rarely associated with osteopetrosis, namely FERMT3 and USB1. Of note, we demonstrated the causative role of four deep intronic mutations in TCIRG1 gene and two different synonymous changes in the TCIRG1 and CLCN7 genes in the pathogenesis of the disease. In addition, WES helped in the differential diagnosis in a patient who was found to bear a mutation in the FAM20C gene, known to cause Raine syndrome. Regarding AFFND1, this is an extremely rare syndrome, comprising facial and skeletal abnormalities, short stature and intellectual disability. WES found a novel truncating mutation in the neuroblastoma-amplified sequence (NBAS) gene in two Indian patients (c.6237-3C>G). This mutation impaired NBAS functions in HEK293T cells overexpressing the truncated NBAS protein. Furthermore, we demonstrated that NBAS expression in mouse embryos was compatible with a role in bone and brain development and that the depletion of endogenous z-nbas in fish embryos resulted in defective morphogenesis of chondrogenic cranial skeletal elements. Overall, we provided evidence supporting the hypothesis of a causative role of the mutated NBAS gene in the pathogenesis of AFFND1. In conclusion, we effectively exploited WES in the genetic diagnosis of rare skeletal diseases. We also highlighted potential limitations of this approach, specifically with respect to deep intronic mutations and synonymous changes, and underlined the importance to complement WES with analysis at the transcript level and functional validation, when possible.
AbstractAn autosomal recessive form of osteopetrosis caused by mutation(s) in at least 8 genes related to osteoclast function. T his condition is characterized by the failure of osteoclasts to resorb bone, resulting in impaired bone modeling/remodeling, and skeletal fragility despite increased bone mass; it is also associated with hematopoietic insufficiency, hypocalcemia, disturbed tooth eruption, nerve entrapment syndromes, and growth impairment. Some cases are also associated with progressive neurological deterioration.
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.
