DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for autosomal recessive osteopetrosis 6 — screening already-approved drugs against its 1-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 6 maps to a 1-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 6 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
Autosomal recessive osteopetrosis 6 is not mentioned by name in any of the three abstracts. The 2018 exome sequencing paper studied a cohort of autosomal recessive osteopetrosis patients and confirmed TCIRG1 as the most frequently mutated gene; it also identified mutations in other known ARO genes and in FERMT3 and USB1, which are very rarely associated with osteopetrosis. That paper found four deep intronic mutations in TCIRG1 and two synonymous changes in TCIRG1 and CLCN7 that were causative. No specific gene is designated as causing a numbered subtype 6 in these abstracts.
A 1990 report describes a family with autosomal dominant osteopetrosis type II that included a severely affected infant presenting with anaemia, hepatosplenomegaly, hydrocephalus and blindness, challenging the usual benign prognosis of the dominant form. The 2025 review states that autosomal recessive osteopetrosis has high endemicity in the Chuvash and Mari El populations of Russia, that the disease is a major medical and social problem due to severe clinical manifestations, low efficacy of pathogenetic therapy, and limitations of etiotropic therapy, and that haematopoietic stem cell transplantation remains the standard treatment. The review notes that alternative treatment methods based on innovative technologies are appearing in the literature but does not name any specific drug or compound.
No clinical trial data, survival rates, response rates, or sample sizes for any treatment of autosomal recessive osteopetrosis 6 are provided in these abstracts. What is missing is any evidence from a controlled trial, any drug candidate tested in patients, any stratification by genetic subtype, and any funding for such work.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Clinical Genetics · 1990 · 17 citations
Autosomal dominant osteopetrosis type II with “malignant” presentation: further support for heterogeneity?
AbstractThe osteopetroses are a heterogeneous group of disorders characterised by generalised bony sclerosis. The autosomal dominant form usually has a "benign" prognosis, in contrast to the "malignant" course of the autosomal recessive variety. In this paper we describe a kindred in which the phenotypic spectrum varied from an asymptomatic condition in adults to a severely affected infant, presenting with anaemia, hepatosplenomegaly, hydrocephalus and blindness. The findings in this family are reported and discussed to elucidate further the possible genetic heterogeneity in autosomal dominant osteopetrosis.
Modern approaches to autosomal-recessive osteopetrosis treatment
AbstractThe review is devoted to modern developments in the treatment of osteopetrosis, the autosomal-recessive form of which has a high endemicity for the indigenous population of Chuvash and Mari El Republicы. Autosomal-recessive osteopetrosis (ARO) is a major medical and social problem, primarily due to the severity of clinical manifestations, low efficiency of pathogenetic therapy and the limitations of etiotropic therapy methods. Until now, the generally accepted standard for treating the autosomal-recessive form is transplantation of pluripotent hematopoietic stem cells. However, information about the development of alternative ARO treatment methods based on innovative technologies appears in medical publications. Therefore, the study of alternative methods of treating this disease is relevant.
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.
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
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.
