DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for SHOX-related short stature — 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 moduleSHOX-related short stature 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 shox-related short stature 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
In a 2009 study of ten peripubertal patients with isolated SHOX defects, five untreated patients showed a marked downward growth shift during puberty, with height SDS falling from –1.2 ± 0.7 at age 11.4 ± 1.4 years to an adult height SDS of –2.5 ± 0.5. Five patients treated with recombinant human growth hormone (rhGH, 50 µg/kg/day) plus depot leuprolide acetate (3.75 mg/month) for 2 to 4.9 years and 1.4 to 5.8 years respectively improved their height SDS from –2.3 ± 1.3 at age 11.8 ± 2.1 years to a final height SDS of –1.7 ± 1.6. The mean change in height SDS was –1.2 ± 0.4 in untreated versus +0.6 ± 0.4 in treated patients, a statistically significant difference (P < 0.001). Four of the five treated patients improved; one did not. This was the first report of adult height gain from combined rhGH and GnRH analog therapy in SHOX deficiency.
A 2017 case series described seven siblings with SHOX haploinsufficiency caused by a novel point mutation (c.582, predicted to truncate the protein at codon 194). The index case was a three-year-old male with height SDS –2.98 and arm span 3 cm less than height. Growth hormone was initiated in all seven siblings after diagnosis, and the authors report improved height SDS without giving numerical final heights or follow-up duration. No control group was included.
A 2011 study (title appears to be misattributed in the abstract text) states that among children with idiopathic short stature, the prevalence of SHOX deficiency is near 1/1000–2000 (1.1–15%). It asserts that real-life data confirm the efficacy and safety of rhGH therapy in SHOX-deficient children regardless of genotype, and that first-year response and age at start significantly affect height gain. However, the abstract provides no patient numbers, no numerical height outcomes, and no long-term follow-up data, only claiming that long-term data are still few.
What is still missing: larger randomised trials with untreated controls, adult height data from long-term follow-up of rhGH-treated SHOX-deficient patients, and any evidence for patient stratification by genotype or pubertal stage. No study has tested whether GnRH analog adds benefit beyond rhGH alone in a controlled design. Funding for such trials remains limited, and no head-to-head comparison of different rhGH doses or regimens exists for this specific population.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
The Journal of Clinical Endocrinology & Metabolism · 2009 · 45 citations · open access
Effectiveness of the Combined Recombinant Human Growth Hormone and Gonadotropin-Releasing Hormone Analog Therapy in Pubertal Patients with Short Stature due to<i>SHOX</i>Deficiency
AbstractCONTEXT: Isolated heterozygous SHOX defects are the most frequent monogenic cause of short stature, and combined therapy with recombinant human GH (rhGH) and GnRH analog (GnRHa) in pubertal patients has been suggested, but there are no data on final height. OBJECTIVE: The aim of the study was to analyze adult height after rhGH and GnRHa therapy in patients with SHOX haploinsufficiency. PATIENTS: Ten peripubertal patients with isolated SHOX defects participated in the study. INTERVENTION: Five patients were followed without treatment, and five were treated with rhGH (50 mug/kg/d) and depot leuprolide acetate (3.75 mg/month). MAIN OUTCOME MEASURES: Adult height sd score (SDS) was measured. RESULTS: All patients followed without treatment had marked downward growth shift during puberty (height SDS, -1.2 +/- 0.7 at 11.4 +/- 1.4 yr; adult height SDS, -2.5 +/- 0.5). Conversely, four of five patients treated with rhGH for 2 to 4.9 yr associated to GnRHa for 1.4 to 5.8 yr improved their height SDS from -2.3 +/- 1.3 at 11.8 +/- 2.1 yr to a final height SDS of -1.7 +/- 1.6. The difference between the mean height SDS at the first evaluation and final height SDS was statistically significant in nontreated vs. treated patients (mean height SDS change, -1.2 +/- 0.4 vs. 0.6 +/- 0.4, respectively; P <0.001). CONCLUSION: A gain in adult height of patients with isolated SHOX defects treated with combined rhGH and GnRHa therapy was demonstrated for the first time, supporting this treatment for children with SHOX defects who have just started puberty to avoid the loss of growth potential observed in these patients during puberty.
Case Reports in Endocrinology · 2017 · 4 citations · open access
Short Stature Homeobox-Containing Haploinsufficiency in Seven Siblings with Short Stature
AbstractDeficiency of the short stature homeobox-containing (SHOX) gene is a frequent cause of short stature in children (2-15%). Here, we report 7 siblings with SHOX deficiency due to a point mutation in the SHOX gene. Index case was a 3-year-old male who presented for evaluation of short stature. His past medical history and birth history were unremarkable. Family history was notable for multiple individuals with short stature. Physical exam revealed short stature, with height standard deviation score (SDS) of -2.98, as well as arm span 3 cm less than his height. His laboratory workup was noncontributory for common etiologies of short stature. Due to significant familial short stature and shortened arm span, SHOX gene analysis was performed and revealed patient is heterozygous for a novel SHOX gene mutation at nucleotide position c.582. This mutation is predicted to cause termination of the SHOX protein at codon 194, effectively causing haploinsufficiency. Six out of nine other siblings were later found to also be heterozygous for the same mutation. Growth hormone was initiated in all seven siblings upon diagnosis and they have demonstrated improved height SDS.
Top-Down versus Bottom-Up Paradigms of Undergraduate Business School Assurance of Learning Techniques. Professional File. Number 119, Winter/Spring 2011.
AbstractAmong children with idiopathic short stature, the prevalence of SHOX-D is near to 1/1000-2000 (1.1-15%) with a wide phenotypic spectrum. Current guidelines support rhGH therapy in SHOX-D children, but long-term data are still few. Our real-life data confirm the efficacy and safety of rhGH therapy in SHOX-D children, regardless of the wide variety of genotypes. Moreover, rhGH therapy seems to blunt the SHOX-D phenotype. The response to rhGH in the first year of treatment and the age when rhGH was started significantly impact the height gain.
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.
