DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for rickets — screening already-approved drugs against its 5-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleRickets maps to a 5-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 rickets 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
carbonic anhydrase 1 (CA1) — CA1 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 phenylsulfonyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7Q0D · 1.24 Å · ligand methyl 4-chloranyl-2-(phenylsulfonyl)-5-sulfamoyl-benzoate (84Z). Experimental structure, not a prediction.
What the evidence adds up to
Cod liver oil has been regarded as the sovereign remedy for rickets based on clinical experience and metabolism tests showing its beneficial effect on calcium retention, but as of 1917 no extensive prophylactic trial with continuous observation had been carried out. A 2018 survey of 150 mothers at a children’s hospital in Taif, Saudi Arabia found that 97.3% of their children had vitamin D deficiency, and the authors concluded that campaigns are needed to spread awareness about vitamin D and its risk factors. A 2022 cross-sectional study of 692 participants in Al-Baha Province, Saudi Arabia reported that 99% had heard of rickets, but knowledge of complications and prevention varied: 55% thought breastfeeding need not stop after diagnosis, 62% would add fortified milk, 67% thought 10–15 minutes of daily sun exposure was suitable, and 46% thought sunrise and sunset were appropriate times for sun exposure. The majority believed failure to grow was the most obvious symptom, inadequate milk the main cause, and exclusive breastfeeding a major risk factor.
X-linked hypophosphatemic rickets (XLH) is caused by inactivating mutations in the PHEX gene. A 2014 study of a sporadic Turkish girl with hypophosphatemic rickets identified a novel 13 bp deletion at the donor splice site of exon 5 (c.663+12del) that activated two nearby cryptic splice donor sites, producing two smaller transcripts that could not translate into functional proteins. Her parents did not carry the mutation, indicating a de novo event. She was treated with calcitriol 0.5 mg/kg/day and oral phosphate supplement with good response.
A 2025 study used a knock-in XLHR mouse model carrying the PHEX variant c.T1349C (p.L450P) and tested gene therapy with a minicircle DNA vector expressing a fragment of FGF23 (amino acids 180–251). In the mice, MC-DNA slightly increased blood phosphorus levels, significantly decreased serum alkaline phosphatase levels, and improved bone mineralization without apparent adverse effects for at least 6 weeks. The authors describe MC-DNA as a promisingly safe and effective therapeutic strategy for XLHR, but the work is limited to a mouse model and a single variant.
What is still missing: large-scale prophylactic trials of cod liver oil that were called for in 1917 have not been reported. The Saudi surveys document widespread vitamin D deficiency and inconsistent parental knowledge but do not test any intervention. The gene therapy approach has only been tested in one mouse model for six weeks; no human trials exist, and the cost and delivery method for MC-DNA in patients are not addressed. No study has stratified patients by genetic subtype or baseline vitamin D status to guide treatment choice.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
JAMA · 1917 · 45 citations
PROPHYLACTIC THERAPY FOR RICKETS IN A NEGRO COMMUNITY
AbstractFor many years cod liver oil has been regarded as the sovereign remedy for rickets. Its claim to therapeutic virtue rests not only on many years of clinical experience but also on metabolism tests showing its beneficial effect on the retention of calcium. It may be properly regarded as one of the well established therapeutic agents and one which should be widely utilized. It seemed, therefore, worth while to investigate whether its usefulness could not be extended to the prophylactic treatment of rickets. No doubt cod liver oil has frequently been employed in individual instances in this way. As far as we know, however, no extensive test, embodying a considerable number of cases and continuous and careful observations, has been carried out. This is the task to which we set ourselves. For various reasons we decided to carry on the investigation among a negro community, and for this purpose selected
The Journal of Pediatrics · 2015 · 28 citations · open access
Comparison of Limestone and Ground Fish for Treatment of Nutritional Rickets in Children in Nigeria
AbstractOBJECTIVE: To determine whether children with calcium-deficiency rickets respond better to treatment with calcium as limestone or as ground fish. STUDY DESIGN: Nigerian children with active rickets (n = 96) were randomized to receive calcium as powdered limestone (920 mg of elemental calcium) or ground fish (952 mg of elemental calcium) daily for 24 weeks. Radiographic healing was defined as achieving a score of 1.5 or less on a 10-point scale. RESULTS: The median (range) age of enrolled children was 35 (6-151) months. Of the 88 children who completed the study, 29 (66%) in the ground fish group and 24 (55%) in the limestone group achieved the primary outcome of a radiographic score of 1.5 or less within 6 months (P = .39). The mean radiographic score improved from 6.2 ± 2.4 to 1.8 ± 2.2 in the ground fish group and from 6.3 ± 2.2 to 2.1 ± 2.4 in the limestone group (P = .68 for group comparison). In an intention to treat analysis adjusted for baseline radiographic score, age, milk calcium intake, and serum 25-hydroxyvitamin D concentration, the response to treatment did not differ between the 2 groups (P = .39). Younger age was associated with more complete radiographic healing in the adjusted model (aOR 0.74 [95% CI 0.57-0.92]). After 24 weeks of treatment, serum alkaline phosphatase had decreased, calcium and 25-hydroxyvitamin D increased, and bone mineral density increased in both groups, without significant differences between treatment groups. CONCLUSION: In children with calcium-deficiency rickets, treatment with calcium as either ground fish or limestone for 6 months healed rickets in the majority of children.
Journal of Pediatric Endocrinology and Metabolism · 2014 · 8 citations
Hypophosphatemic rickets caused by a novel splice donor site mutation and activation of two cryptic splice donor sites in the PHEX gene
AbstractX-linked hypophosphatemic rickets (XLH) is the most common inherited form of rickets. XLH is caused by inactivating mutations in the PHEX gene and is transmitted as an X-linked dominant disorder. We investigated PHEX mutation in a sporadic Turkish girl with hypophosphatemic rickets. The patient was 2 years of age with a complaint of inability to walk. She had bowing of legs and growth retardation. Laboratory data showed normal calcium, low phosphate with markedly elevated ALP, and low phosphate renal tubular reabsorption. She was treated with Calcitriol 0.5 mg/kg/day and oral phosphate supplement with good response. The entire coding region of PHEX gene was sequenced from patient's peripheral leukocyte DNA and a novel 13 bp deletion at the donor splice site of exon5 was found (c.663+12del). Instead of using the donor splice site of intron 4 to splice out exon 5 and intron 5, the spliceosome utilized two nearby cryptic donor splice sites (5' splice site) to splice out intron 4, resulting in two smaller transcripts. Both of them could not translate into functional proteins due to frameshift. Her parents did not carry the mutation, indicating that this is a de novo PHEX mutation likely resulting from mutagenesis of X chromosome in paternal germ cells. We conclude that c.663+12del is a novel mutation that can activate nearby cryptic 5' splice sites. The selection of cryptic 5' splice sites adds the complexity of cell's splicing mechanisms. The current study extends the database of PHEX mutation and cryptic 5' splice sites.
The Egyptian Journal of Hospital Medicine · 2018 · 3 citations · open access
Knowledge and Attitude Practice (KAP) of Rickets Disease among Mothers in KSA
AbstractBackground: Rickets is one of the emerging diseases around the world and its records have been frequently increased among Saudi children. Objective: Our aim of the study was to discuss and improve the knowledge and the awareness of mothers in the Kingdom of Saudi Arabia about rickets disease and its environmental and nutritional risk factors. Methods: We conducted this cross-sectional retrospective Study at the maternal Children Hospital in Taif, Saudi Arabia. Data were collected using a pre-specified questionnaire after obtaining the patients consent. SPSS software was used to analyze the data. Results: We included 150 mothers with their children. There were 146 (97.3%) of the children with vitamin D deficiency. Conclusion: In Saudi Arabia, there is a need for campaigns that spread awareness among mothers and young adult females about the importance of vitamin D, diets containing adequate levels of it as well the risk factors that cause its deficiency.
International Journal of General Medicine · 2022 · 1 citations · open access
Perception of Rickets Disease Among Parents in Al-Baha Province, Saudi Arabia
AbstractIntroduction: Rickets involves the softening of bones in children and osteopenia with disordered calcification, leading to a higher proportion of osteoid tissue prior to epiphyseal closure in children. Rickets is common in the Middle East, Africa, and Asia. The peak age of prevalence is 3-18 months. Signs include bone tenderness, easy fracture, early bone deformity, delayed closure of fontanelles, and softening of skull bones (craniotabes). Objective: This study assesses knowledge in the AlBaha region about rickets' clinical presentation, causes, complications, and prevention, as well recommendations to educate the community. Methods: In this descriptive cross-sectional study, a questionnaire was administered to people in the AlBaha region to assess knowledge related to rickets in children. The sample size was calculated using calculator.net, and the Statistical Package for Social Sciences (SPSS) version 2 was used for analyses with P < 0.05 used for significance. Results: Of the 692 participants, only 5% reported rickets in their children, but the majority (99%) had heard about rickets. Participants' knowledge of rickets' complications was highest for spinal vertebral deformities and lowest for skin deformities. 55% of the participants thought there was no need to stop breast-feeding once rickets is diagnosed, 62% preferred to add fortified milk to the diet, 67% thought that a suitable duration for sunlight exposure is 10 to 15 minutes per day, and 46% thought that sunrise and sunset are suitable times for sun exposure. Preventive measures were believed to depend on having enough exposure to sunlight (77% of participants) and eating vitamin-D rich foods (63%). The majority believed that failure to grow is the most obvious symptom, inadequate milk is the main cause, and exclusive breast-feeding is a major risk factor. Conclusion: Most people have heard about rickets, but knowledge about complications and prevention varies.
Advanced Science · 2025 · 1 citations · open access
Treatment with Minicircle DNA Expressing a FGF23 Fragment in a Clinically relevant Mouse Model of X‐Linked Hypophosphatemic Rickets
AbstractX-linked hypophosphatemic rickets (XLHR) is a rare X-linked dominant skeletal dysplasia caused by phosphate regulating endopeptidase homolog X-linked (PHEX) gene mutation. Until now, the pathogenic role of PHEX has not been fully determined, and there has been no radical cure for XLHR. In the previous study, a novel PHEX variant (c.T1349C; p.L450P) is identified in a child with XLHR. The present study aims to reveal its pathogenic role and evaluate the therapeutic effects of the minicircle (MC)-DNA in XLHR. In vitro, the wildtype and mutant plasmids are introduced into HEK293 cells. In vivo, a new knock-in XLHR mouse model carrying the novel variant is established. Furthermore, this study makes the first attempt to perform gene therapy using a MC-DNA vector expressing a fragment of FGF23 (amino acids 180-251) in the Phex-T1349C mice. The new mouse model demonstrates the clinical manifestations of XLHR seen in the patient, including a gene dosage effect. Furthermore, MC-DNA is found to slightly increase blood phosphorus levels, significantly decrease serum alkaline phosphatase levels, and improve bone mineralization without apparent adverse effects for at least 6 weeks. This study suggests MC-DNA as a promisingly safe and effective therapeutic strategy to treat XLHR.
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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