DeCure for Autosomal recessive hypophosphatemic rickets
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for autosomal recessive hypophosphatemic 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 moduleAutosomal recessive hypophosphatemic 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 autosomal recessive hypophosphatemic 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.
What the evidence adds up to
A 2014 case report describes a two-year-old girl with a novel de novo 13-base-pair deletion in the PHEX gene (c.663+12del) that activated two cryptic splice donor sites, producing two non-functional transcripts. She was treated with calcitriol 0.5 mg/kg/day and oral phosphate supplement and showed good response. A 2013 case report of a three-year-old boy with X-linked hypophosphatemic rickets (XLH) documented low serum phosphate (0.45 mmol/L), high alkaline phosphatase (1864 IU/L), and low 1,25-dihydroxyvitamin D3, with normal calcium, parathyroid hormone, and 25-hydroxyvitamin D3. After treatment with calcitriol and phosphates, his laboratory values and radiographic bone changes resolved. Both reports are single cases, not controlled trials, and neither provides long-term follow-up data on growth or bone deformity correction.
A 2007 review explains that the discovery of phosphatonins, particularly fibroblast growth factor 23 (FGF23), and the identification of mutations in PHEX, the sodium-phosphate cotransporter NaPiIIc, and the bone matrix protein DMP1 have clarified the pathophysiology of hypophosphatemic rickets. The review states that these findings open the way to new treatment strategies but does not name any specific new drug or report clinical outcomes from such strategies. No drug other than calcitriol and phosphate supplements is mentioned in any of the three abstracts.
What is still missing: randomised controlled trials comparing standard calcitriol and phosphate therapy against any new agent, long-term outcome data on final height and bone health in treated patients, and validated biomarkers to stratify patients by genetic subtype. No trial funding or specific trial design is reported in these abstracts.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Current Opinion in Pediatrics · 2007 · 12 citations
Regulation of phosphate homeostasis in infants, children, and adolescents, and the role of phosphatonins in this process
AbstractPURPOSE OF REVIEW: Unlike calcium metabolism, the control of phosphate homeostasis has long been poorly understood. The identification of 'phosphatonins' in the serum of hypophosphatemic patients, the unveiling of the genetic causes of hypo and hyperphosphatemic diseases in patients, and the creation of finely adapted animal models have revolutionized our understanding of phosphate homeostasis. RECENT FINDINGS: Original reports published in 2006/2007 bring valuable pieces of information that enable better understanding of the physiological regulation of phosphate homeostasis by more precisely defining the interplay between PHEX, vitamin D, and phosphatonins; identification of new genes causing hypophosphatemic rickets, aside from PHEX and fgf23, namely the genes encoding for a renal sodium-phosphate cotransporter, NaPiIIc, and for a bone matrix protein, DmpI; and improved diagnosis of tumor-induced osteomalacia with more precise imaging techniques for tumor localization and more precise fibroblast growth factor 23 assays. SUMMARY: From a clinical point of view, these findings offer new tools for the diagnosis of hypophosphatemic rickets (biologic, genetic, imaging techniques) and open the way to new treatment strategies.
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.
AbstractAIM: The aim of this work was the presentation of one case with X-linked hypophosphatemic rickets. METHODS: Diagnosis has been established based on the anamnesis, physical examination, anthropometric measurements, laboratory tests and radiological examination. RESULTS: A male patient (age 3 years) has been hospitalized due to the growth delay, bone deformity, bone pain and walking difficulties. The laboratory tests have revealed that the calcium value was in the reference range, that of phosphates was low (0.45 mmol/L), the alkaline phosphatase value was quite high (1864 IU/L), the value of parathyroid hormone and of 25- hydroxyvitamin D3 were in the reference ranges, whereas the value of 1,25- dihydroxyvitamin D3 was low. Radiographic changes were evident and typical in the distal metaphysis of radius and ulna as well as in the bones of the lower limbs. After treatment with synthetic analog of vitamin D3--calcitriol and phosphates, the above mentioned laboratory test values and the radiographic changes in bones withdrew. CONCLUSION: X- linked hypophosphatemic rickets is a rare disease inherited through X chromosome, and its treatment includes a constant use of calcitriol and phosphates with the aim of avoidance of clinical and laboratory manifestations.
Pan African Medical Journal · 2018 · 3 citations · open access
X-linked vitamin D-resistant rickets: 12 years of follow-up
AbstractRickets are abnormalities of mineralization that can lead to bone fractures and deformities. Vitamin-resistant rickets is defined as any rickets not prevented by regular, early and prolonged administration of vitamin D and not cured by a sufficient total dose. The aim of our work is to describe the clinical, paraclinical and therapeutic aspects of X-linked hypophosphatemic rickets (XLHR), which is the most common cause of hereditary rickets and on the other hand to highlight the interest not only of the early care but also the regular long-term monitoring of these children.
International Journal of Advances in Medicine · 2019 · 0 citations · open access
Rare cause of pathological fracture in adults as hypophosphatemic rickets
AbstractHypophosphatemic rickets is a disorder of defective bone minerlization due to defect in renal phosphate handling process. It is characterised by increased phosphate excretion accompanied by increased phosphatonins like fibroblast growth factor 23. It can be hereditary form of X linked, autosomal dominant, autosomal recessive type of hypophosphatemic rickets. It is associated with low serum phosphorus, normal serum calcium, inappropriately low to normal vitamin D level. Correct identification of these disorders is important for determining therapy. Early diagnosis and management prevent subsequent complication of 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.
