DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for osteoporosis-pseudoglioma syndrome — 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 moduleOsteoporosis-pseudoglioma syndrome 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 osteoporosis-pseudoglioma 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.
What the evidence adds up to
A 2011 case report describes a 19-year-old man with osteoporosis-pseudoglioma syndrome, congenital blindness, and low-trauma fractures. After six years of intravenous pamidronate (the last three of which had minimal effect on bone mineral density), he received two years of teriparatide 20 µg/day. Lumbar spine bone mineral density increased by 9.7% and right femur hip by 10.2%. Serum markers CTX rose early, peaking at month 3, followed by P1NP peaking at month 9; both returned to baseline by month 24. No adverse events were reported. The authors note that the CTX rise preceding the P1NP rise is an unusual time course for teriparatide, possibly typical of low bone turnover states.
A 2023 review states that osteoporosis-pseudoglioma syndrome is a rare autosomal recessive disorder of severe juvenile osteoporosis and congenital blindness, with intellectual disability, short stature, fractures, thinning of bones, bowing of extremities, and spinal deformities. A separate 2023 case report concerns a 52-year-old woman with osteogenesis imperfecta (not osteoporosis-pseudoglioma syndrome) who received romosozumab 210 mg monthly for 12 months after alendronate had not improved bone density. Her spine bone mineral density increased by 10.3% and right hip by 5.4%, with a 5.2% increase in trabecular bone score. The authors state that current literature on sclerostin inhibitors in osteogenesis imperfecta is limited.
A 2007 study of 19 glioma patients (not osteoporosis-pseudoglioma syndrome) found that 38% had osteopenia and 16% had osteoporosis, attributed to anticonvulsants and glucocorticoids. A 2017 commentary notes that new osteoporosis drugs are in development but that a "treatment gap" persists between patients who would benefit and those receiving treatment.
No controlled trial of any drug has been conducted in osteoporosis-pseudoglioma syndrome. The available evidence is limited to single case reports. What is missing is any randomised trial, any head-to-head comparison of teriparatide with other agents in this specific population, any data on fracture reduction rather than bone density alone, and any systematic effort to stratify patients by LRP5 mutation type.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Bone and Mineral Research · 2011 · 24 citations
Teriparatide increases bone mineral density in a man with osteoporosis pseudoglioma
AbstractOsteoporosis Pseudoglioma (OPPG) is characterized by severe juvenile-onset osteoporosis and ocular abnormalities. It is caused by one of several inactivating mutations in LRP5, a gene importantly involved in bone formation. The objective of this study was to evaluate the efficacy of teriparatide in a young man with OPPG. The subject of this case report is a 19-year-old man with congenital blindness and low trauma fractures because of OPPG. A 2-year course of teriparatide, 20 µg/day, was initiated after a 6-year course of intravenous pamidronate infusions, the latter 3 years of which had minimal effects on bone mineral density (BMD). Measurements in serum were made of C-terminal telopeptide of type I collagen (CTX), N-terminal propeptide of type I collagen (P1NP), total and ionized calcium, phosphate, uric acid, complete blood count, and renal and liver function tests. Urinary calcium/creatinine ratio was determined. BMD was measured by DXA yearly. BMD increased by 9.7% in lumbar spine and 10.2% in right femur hip. CTX rose early, peaking in month 3, followed by an increase in P1NP, peaking in month 9. Both indices returned to baseline by month 24. The increase in CTX followed by P1NP is an unusual time course when teriparatide is used to treat osteoporosis but may be typical of low bone turnover states. There were no adverse events. In a patient with OPPG, teriparatide markedly increased BMD in the lumbar spine and femur hip.
Expert Opinion on Drug Discovery · 2014 · 20 citations
Status of drug development for the prevention and treatment of osteoporosis
AbstractINTRODUCTION: The metabolic bone disease osteoporosis is a growing health and health-economic problem worldwide. Bisphosphonates are the most widely used antiresorptive medication and the de facto gold standard in fracture prophylaxis all over the world, in conjunction with calcium and vitamin D supplementation. Several new medications for the treatment of postmenopausal osteoporosis are in the pipeline. AREAS COVERED: The authors present the most recent studies on new and current antiresorptive as well as anabolic drugs. Specifically, the authors present the current knowledge on drugs directed against cathepsin K and sclerostin as well as the new pathways of interest from preclinical studies. EXPERT OPINION: New scientific results have identified novel signaling pathways as potential targets for future development of anti-osteoporotic drugs. The treatments close to marketing at the moment are odanacatib and romosozumab and these are both promising new medications based on bone mineral density results, safety profile and administration. Theoretically, romosozumab may hold the potential to be a drug to 'cure' even advanced stages of osteoporosis with short-term treatment. However, safety, fracture data and cost are key elements that will determine the extent of use.
AACE Clinical Case Reports · 2023 · 8 citations · open access
Osteoporosis Improved by Romosozumab Therapy in a Patient With Type I Osteogenesis Imperfecta
AbstractBackground/Objective: Osteogenesis imperfecta (OI) is a genetic disorder that affects type 1 collagen synthesis causing increased bone fragility, low bone mass, and skeletal deformity. Bisphosphonates are recommended for treatment of OI patients; however, the efficacy of sclerostin inhibitors such as romosozumab has not been determined in OI patients with osteoporosis. Case Report: A 52-year-old G2P2 clinically diagnosed with OI, with a history of multiple fractures beginning in childhood presented with low bone mass. On physical examination, blue sclera was observed. She was previously treated with alendronate therapy from April 2014 to June 2015 without significant improvement in bone mineral density (BMD). After the onset of menopause, she began romosozumab 210 mg subcutaneous therapy once a month for 12 months. Repeat dual-energy X-ray absorptiometry showed an increase of 10.3% in BMD of the spine and a 5.4% increase in BMD of the right hip. The trabecular bone score increased by 5.2%. Discussion: Current literature is limited regarding the use of sclerostin inhibitors in OI patients. Our patient's improvement in BMD of the spine and right hip after romosozumab therapy was significant at a 95% confidence level, compared to treatment initiation. Her trabecular bone score also improved significantly. Six months into our patient's treatment course, a case in Japan of a male with severe osteoporotic OI and recurrent fractures showed improvement in BMD after romosozumab therapy. Conclusion: This case highlights our patient's significant response to romosozumab and warrants further investigation of romosozumab as a potential treatment option for OI patients with osteoporosis.
touchREVIEWS in Endocrinology · 2017 · 1 citations · open access
Progress and Problems in Bone and Mineral Disorders
AbstractA number of new drugs are moving through the osteoporosis therapy pipeline. Some show great promise for patients while one has fallen by the wayside at the last hurdle. New, effective therapies are warmly welcomed but there are still uncertainties around management of osteoporosis with currently available drugs that are contributing to what is commonly being referred to as the 'treatment gap'; a differential between those patients who would benefit from treatment versus those who actually are receiving it. Furthermore, in parallel to the common public health disease of osteoporosis, there have been tangible developments in therapies available for some rare bone and calcium diseases.
[The sequential therapy of romosozumab followed by denosumab for osteoporosis.]
AbstractRomosozumab is a bone-forming agent with a dual effect of increasing bone formation and decreasing bone resorption by inhibiting sclerostin. In the pivotal Fracture study in postmenopausal women with osteroposis(FRAME)and the extension trial, 12 months of romosozumab led to persistent fracture, especially new vertebral fracture, reduction benefit and ongoing BMD(bone mineral density)gains when follow 24 months of denosumab. The sequence therapy of romosozumab followed by denosumab may be a promising regimen for the treatment of osteoporosis.
Scientific Repository of Open Access of Portugal (RCAAP) · 2023 · 0 citations · open access
Osteoporosis-Pseudoglioma Syndrome, a Rare Entity
AbstractOsteoporosis-pseudoglioma syndrome is a rare autosomal recessive disorder of severe juvenile osteoporosis and congenital blindness. This disease is characterized by intellectual disability, osteoporosis of bones, and eye abnormalities. It is usually diagnosed in early childhood, with affected children displaying early onset blindness, severe osteoporosis, short stature, and fractures. On plain radiographs, patients usually manifest severe thinning of bones, bowing of extremities, and spinal deformities.
Prevalence of osteoporosis in glioma patients on enzyme inducing anticonvulsants (EIAC) and/or glucocorticoids
Abstract19527 Background: Glioma patients are at risk for osteoporosis and associated morbidity as a result of neurological deficits, anticonvulsants and glucocorticoid therapy. The prevalence of osteoporosis in glioma patients has not been reported. We hypothesized that the prevalence of the osteopenia (defined by bone mineral density (BMD) T-score < -1) or osteoporosis (defined by T- score < -2: spine; T-score < - 2.5: femur) in glioma patients supports consideration of bisphosphonate treatment to prevent or reduce the severity of osteoporosis and skeletal complications. Methods: BMD was conducted on 19 eligible patients. Eligibility criteria included: (1) histologically confirmed diagnosis of a primary glioma, (2) age ≥ 18 years, (3) KPS ≥ 60%, (4) treated with valproate or an EIAC and/or on more than physiologic replacement steroid therapy, (5) creatinine < 2.0 mg/dl and calculated creatinine clearance of >60 ml/min, (6) bilirubin < 1.5 x nl, LFTs < 2.5 x nl, (7) recovery from surgery, (8) life expectancy >12 wks, and (9) written informed consent. Exclusion criteria: Previously diagnosed with osteoporosis requiring oral bisphosphonates. Results: 89% were diagnosed with a glioblastoma. Mean age, 54.6 (±SD 9.4; range 35–70). 68% (13/19) were male and all were white race. 53% (10/19) had a KPS of ≥90: 42% (5/19) KPS ≥80: 5% (1/19) KPS ≥70%. AC use: 64% phenytoin; 11% valproate; 5% phenobarbital; 5% oxcarbazepine; 10% levetiracetam; and 5% none. 37% were on dexamethasone, 16% other steroids, and 47% off steroids. Mean N-telopeptide (a marker of bone turn over) was 12.6 (±SD 5.5; range 5.6–22.2). 22% of patients (4/19) had osteopenia and 16% (3/19) had osteoporosis. Conclusions: Overall 38% percent of glioma patients had evidence of osteopenia and 16% had osteoporosis. Thus, bisphosphonates should be considered to prevent skeletal complications. Subsequently, we have initiated an open-labeled Phase II trial to further determine the prevalence of osteoporosis in glioma patients and the effect of every three month prophylactic zoledronic acid on bone density. An update of the prevalence of osteoporosis in patients enrolled on this trial will be presented. No significant financial relationships to disclose.
BMJ Case Reports · 2009 · 0 citations · open access
Radiological findings in cyclical administration of intravenous pamidronate in children with osteoporosis
AbstractA 5-year-old boy with moderately severe osteogenesis imperfecta and spontaneous fractures was treated with serial courses of intravenous pamidronate. Pamidronate is a second-generation bisphosphonate drug that binds strongly to bone mineral and interferes with bone remodelling by slowing osteoclastic bone resorption. It is used in a cyclic dosage of 1 mg/kg/day intravenously on 3 successive …
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.
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