DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for autosomal recessive osteopetrosis 2 — 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 2 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 2 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
TNF superfamily member 11 (TNFSF11) — TNFSF11 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5BNQ · 2.8 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Autosomal recessive osteopetrosis 2 is one of the rare genetic skeletal disorders within the autosomal recessive osteopetroses group, which has an estimated frequency of 1:250,000 worldwide. The most severe form, OPTB5, results from homozygous mutation in the OSTM1 gene, accounting for approximately 5% of autosomal recessive osteopetrosis cases. OSTM1 mutations lead to a highly debilitating form of the disease in infancy and death within the first few years of life. The OSTM1 protein trafficking function is essential for osteoclast maturation, and the protein also plays a primary and direct role in the central nervous system.
The autosomal dominant form of osteopetrosis, type II, usually has a benign prognosis, but one 1990 report describes a kindred where the phenotypic spectrum varied from asymptomatic adults to a severely affected infant presenting with anaemia, hepatosplenomegaly, hydrocephalus, and blindness. A 2009 case report describes a patient diagnosed with autosomal dominant osteopetrosis type II in his youth who later developed rheumatoid arthritis at age 42; despite severe inflammation and rapid cartilage destruction, the progression of bone erosion was slow. Several case reports describe asymptomatic adolescents with the autosomal dominant form, including a 14-year-old boy and a 14-year-old girl.
The malignant recessive form in infants is characterised by bicytopenia, and a 2021 case report emphasises the severity of ocular and bone damage, stating that early marrow transplant alone seems to cure the disease. A 2000 report notes that molecular confirmation was done in 3 cases and discusses genetic heterogeneity in clinical presentation. What remains missing are targeted therapies developed from understanding epigenetic alterations and population-specific variants, as well as larger systematic studies that could stratify patients by genotype to predict which infants might benefit from early transplant versus those with OSTM1 mutations who may have additional neurodegenerative components that transplant does not address.
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.
Rheumatoid arthritis associated with osteopetrosis
AbstractOsteopetrosis is an inherited disorder characterized by reduced bone resorption. We here report a rare case of osteopetrosis associated with rheumatoid arthritis. The patient was diagnosed as autosomal dominant osteopetrosis type II in his youth and developed rheumatoid arthritis at 42 years of age. In spite of the severe inflammation and rapid progression of cartilage destruction, the progression of bone erosion was slow in this patient.
OSTM1 pleiotropic roles from osteopetrosis to neurodegeneration
AbstractAutosomal recessive osteopetroses (ARO) are rare genetic skeletal disorders of high clinical and molecular heterogeneity with an estimated frequency of 1:250,000 worldwide. The manifestations are diverse and although individually rare, the various forms contribute to the prevalence of a significant number of affected individuals with considerable morbidity and mortality. Among the ARO classification, the most severe form is the autosomal recessive-5 (OPTB5) osteopetrosis (OMIM 259720 ) that results from homozygous mutation in the OSTM1 gene (607649). OSTM1 mutations account for approximately 5 % of instances of autosomal recessive osteopetrosis and lead to a highly debilitating form of the disease in infancy and death within the first few years of life (Sobacchi et al., 2013) [1] . • OSTM1 is the more severe form of ARO in mice and humans. • The OSTM1 protein trafficking function is essential for osteoclast maturation. • OSTM1 plays a primary and direct role in the central nervous system.
International Journal of Medical and Dental Case Reports · 2016 · 6 citations
Osteopetrosis: A case report
AbstractOsteopetrosis is an uncommon skeletal disorder characterized by generalized sclerosis of bones due to defective osteoclast function. A wide variation in clinical severity of the disease may be noted. Radiographic features are usually diagnostic. A case of benign autosomal dominant form of osteopetrosis in an asymptomatic 14-year-old boy is hereby reported.
AbstractOsteopetrosis is a disorder characterized by high bone density, hepatosplenomegaly, visual and hearing loss, and anemia. Pycnodysostosis presents with short stature, acroosteolysis, and dense bones. We, hereby, present here a family with autosomal dominant osteopetrosis and also children with recessive osteopetrosis and pycnodysostosis. The molecular confirmation was done in 3 cases. Genetic heterogeneity in clinical presentation is discussed here. Further studies will help in identifying epigenetic alterations and population-specific variants and also developing targeted therapies.
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
Journal of Advances in Medicine and Medical Research · 2021 · 0 citations · open access
Malignant Osteopetrosis, a Rare Cause of Bicytopenia in Infants: A Case Report
AbstractOsteopetrosis is an autosomal metabolic bone disease caused by a functional abnormality of the osteoclasts. Two main forms exist, the dominant benign form and the recessive malignant form. We describe in our patient the recessive malignant form retained according to all the clinical, biological and especially radiological criteria. We also report in this work the elements of description of the disease in the literature in comparison with the data of our patient, which allows us to emphasize the severity of the ocular and bone damage requiring an early marrow transplant which alone seems to cure the disease.
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.
