DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for vitamin D-dependent rickets — 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 moduleVitamin D-dependent rickets 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 vitamin d-dependent 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
vitamin D receptor (VDR) — VDR 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 1~{s},3~{z}drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8IQN · 1.639 Å · ligand (1~{S},3~{Z})-3-[(2~{E})-2-[(1~{R},3~{a}~{S},7~{a}~{R})-1-[(2~{R})-5,5-bis(fluoranyl)-6-methyl-6-oxidanyl-heptan-2-yl]-7~{a}-methyl-2,3,3~{a},5,6,7-hexahydro-1~{H}-inden-4-ylidene]ethylidene]-4-methylidene-cyclohexan-1-ol (SRF). Experimental structure, not a prediction.
What the evidence adds up to
Vitamin D dependent rickets describes a group of genetic disorders in which patients cannot maintain adequate concentrations of active vitamin D or cannot respond fully to it, and therefore require lifelong specialised vitamin D replacement regimens. The three molecular forms of the condition are reviewed, along with current management protocols. No trial data for the genetic forms are provided in these abstracts.
Two randomised controlled trials examined treatment of nutritional rickets, not the genetic vitamin D dependent form. In 61 children aged 0.5 to 5 years with nutritional rickets, 600 000 IU given as a single intramuscular injection was compared with 60 000 IU given orally once a week for 10 weeks. At 12 weeks, no difference in biochemical or radiological parameters was found between the two regimens. Serum 25‑hydroxy vitamin D exceeded 100 ng/mL in two children in the oral group and one in the intramuscular group. No child developed hypercalcaemia or hypercalciuria after starting treatment.
In a separate trial, 110 children aged 6 months to 5 years with nutritional rickets were randomised to a single oral dose of either 90 000 IU or 300 000 IU vitamin D. Eighty‑six children completed the study. The radiographic score fell from 6.90 to 0.16 in the 90 000 IU group and from 6.93 to 0.23 in the 300 000 IU group. Serum levels of 25‑hydroxy vitamin D, alkaline phosphatase, and parathyroid hormone were similar between groups at baseline and follow‑up. Hypercalciuria, hypercalcaemia, and hypervitaminosis D were seen more often in the 300 000 IU group. No clinical adverse events occurred. The authors concluded that 90 000 IU as a single oral dose is safe and effective for healing nutritional rickets.
What is still missing for vitamin D dependent rickets specifically: no trial data exist in these abstracts for the genetic forms; no randomised controlled trials have been conducted in that population; no comparisons of different vitamin D analogues or dosing schedules are provided; and no information on long‑term outcomes, adverse effects, or optimal monitoring strategies is available. Funding for trials in rare genetic rickets, appropriate patient stratification by genotype, and standardised outcome measures remain absent.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Frontiers in Pediatrics · 2020 · 93 citations · open access
Diagnosis and Management of Vitamin D Dependent Rickets
AbstractThe term "vitamin D dependent rickets" describes a group of genetic disorders that are characterized by early-onset rickets due to the inability to maintain adequate concentrations of active forms of vitamin D or a failure to respond fully to activated vitamin D. Although the term is now admittedly a pathophysiological misnomer, there remains clinical relevance for its continued use, as patients have a lifelong "dependency" on administration of specialized regimens of vitamin D replacement. This review provides an update on the molecular bases for the three forms of vitamin D dependent rickets, and summarizes current protocols for management of affected subjects.
The Journal of Clinical Endocrinology & Metabolism · 2012 · 86 citations
Role of Calcium Deficiency in Development of Nutritional Rickets in Indian Children: A Case Control Study
AbstractCONTEXT: Nutritional rickets is usually attributed to vitamin D deficiency. Studies from some tropical countries have postulated low dietary intake of calcium as the cause of nutritional rickets. Both vitamin D and dietary calcium deficiency are highly prevalent in India. Information on their relative contribution in the development of rickets in Indian children is limited. OBJECTIVE: The aim was to study the role of calcium and vitamin D deficiency in causation of nutritional rickets in young Indian children. DESIGN AND METHODS: In a case-control study, 67 children with nutritional rickets and 68 age- and sex-matched healthy controls were compared for demographic factors, nutritional status, sun exposure (UV score), dietary calcium and phytate intake (for subjects not breast-fed at presentation), and biochemical parameters [serum calcium, inorganic phosphate, alkaline phosphatase, 25-hydroxyvitamin D (25OHD), and PTH]. RESULTS: Mean intake of calcium (204±129 vs. 453±234 mg/d; P<0.001) and proportion of calcium from dairy sources (41.7 vs. 88.6%; P<0.001) were significantly lower in cases vs. controls. The dietary intake of phytate was also significantly higher in cases (P=0.01). Median serum 25OHD level (interquartile range) in both cases and controls was in the range of deficiency [13.7 (10; 17.9) and 19.4 (12.3; 24.6) ng/ml, respectively]. There was no significant difference in the serum 25OHD level (P=0.08) or sun exposure as measured by UV score (P=0.39) among the cases and controls. In cases with rickets, significant negative correlations were seen between dietary calcium intake and radiological score (r=-0.28; P=0.03) and PTH (r=-0.26; P=0.02). No correlation was found between serum 25OHD level and radiological score or biochemical parameters of rickets. CONCLUSIONS: Rickets develops when low dietary calcium intake coexists with a low or borderline vitamin D nutrition status.
Journal of Tropical Pediatrics · 2014 · 43 citations · open access
A Randomized Controlled Trial on Safety and Efficacy of Single Intramuscular versus Staggered Oral Dose of 600 000IU Vitamin D in Treatment of Nutritional Rickets
AbstractOBJECTIVE: Comparison of efficacy and safety of two different regimens of vitamin D-600 000 IU as a single intramuscular dose, and 60 000IU orally once a week for 10 weeks-in treatment of nutritional rickets. METHODS: Children with nutritional rickets (age: 0.5-5 years, n = 61) were randomized to receive either 60 000IU vitamin D orally once a week for 10 weeks or 600 000IU single intramuscular injection. Serum calcium, phosphate, alkaline phosphatase, urinary calcium/creatinine ratio, serum 25 hydroxy vitamin D and radiological score were compared at 12-week follow-up. RESULTS: No difference was found in efficacy of the two regimens on comparing biochemical and radiological parameters. Serum 25 hydroxy vitamin D >100 ng/ml was found in two children in the oral group and one child in the intramuscular group. No child developed hypercalcemia or hypercalciuria after starting treatment. CONCLUSION: Staggered oral and one-time intramuscular administrations of 600 000IU vitamin D are equally effective and safe in treatment of nutritional rickets.
Indian Journal of Endocrinology and Metabolism · 2018 · 12 citations · open access
Efficacy and Safety of 90,000 IU versus 300,000 IU Single Dose Oral Vitamin D in Nutritional Rickets: A Randomized Controlled Trial
AbstractAIM: To compare efficacy and safety of 90,000 IU versus 300,000 IU oral single dose vitamin D for treatment of nutritional rickets. STUDY DESIGN: Randomized controlled trial. SETTING: Tertiary care hospital. PARTICIPANTS: One hundred ten children (6 months to 5 years, median age 10.5 months) with rickets. Exclusion criteria were disease affecting absorption, intake of calcium/vitamin D preparation in last 6 months, abnormal renal function, and rickets other than nutritional. INTERVENTION: = 55). METHODOLOGY: Severity of rickets was scored on knee and wrist X-ray as per Thacher's radiographic score. Baseline serum levels of calcium, SAP, 25(OH)D, iPTH were measured. Follow up was done at 1 week, 4 weeks, and 12 weeks. OUTCOME VARIABLE: Primary - Radiographic score at 3 months. Secondary - Serum levels of 25(OH)D, SAP, and iPTH at 3 months, clinical and biochemical adverse effects. RESULTS: Eighty-six subjects (43 in each group) completed the study. The radiographic score reduced from 6.90 to 0.16 in group A and from 6.93 to 0.23 in group B. The levels of 25(OH)D, ALP, and PTH were similar between the groups at baseline and follow up. Hypercalciuria and hypercalcemia were seen more often in group B as was hypervitaminosis D. There were no clinical adverse events. CONCLUSIONS: Single oral dose vitamin D3 90,000 IU is safe and effective in achieving healing of rickets.
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.
