DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Laron syndrome — 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 moduleLaron syndrome 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 laron 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.
Molecular view
growth hormone receptor (GHR) — GHR 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 1A22 · 2.6 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
In a multicentre study sponsored by Pharmacia & Upjohn, 33 patients with Laron syndrome (31) or hGH-1 gene deletion (2) were treated with subcutaneous IGF-I (Igef) at 40–120 µg/kg twice daily after meals. Seventeen patients treated for 48 months or longer were analysed; six were treated up to 72 months. Mean age at start was 9.1 years (range 3.7–13.5), mean height SDS –6.5. At end of observation mean age was 14.2 years (9.1–17.7), mean height SDS –4.9. All patients showed a significant increase in growth during the final year on IGF-I, with two reaching the age-corresponding 3rd centile. Total gain in height SDS was 1.7. Gain correlated negatively with age at start of treatment (R² = –0.78, p < 0.02). BMI SDS rose from 0.6 to 1.8 over the observation period. The authors concluded long-term treatment promoted growth and that early start offered potential for height normalisation, but noted treatment modalities needed optimisation.
Three descriptive case series from India report clinical and biochemical features of Laron syndrome in children. A 2014 study of nine children (age at presentation 2.5–11.5 years) found mean height Z-score –5.2 on Indian charts but within ±2 SD on Laron-specific charts. Mean BMI Z-score was 0.92. All had low IGF-I (<5th percentile) and IGFBP-3 (<0.1st percentile), high basal and stimulated GH (basal mean 13.78 ng/mL, stimulated mean 46.29 ng/mL), and poor response to IGF-I generation test. Three boys had micropenis, one had undescended testis. A 2023 study of five South Indian children (mean age 5.9 years, mean age at diagnosis 2.7 years) reported mean height Z-score –7.0, weight Z-score –5.9, BMI Z-score –0.1. Median basal GH was 13 ng/mL; post-stimulation GH peaked at 50 ng/mL. All had IGF-I below 3rd percentile with no increment on generation test. Micropenis was present in all three boys; one child had symptomatic hypoglycaemia. Genetic analysis in two boys found variants in the growth hormone receptor gene.
A 2025 summary of a cohort of 76 patients with Laron syndrome followed from infancy into adulthood describes disabilities and handicaps arising from longstanding IGF-I deficiency. These include dwarfism, progressive obesity, diabetes, fatty liver, cardiovascular disease, neurological and orthopaedic problems, and difficulties in vocational training, occupation and social life, all lowering quality of life. The authors state that early initiation of IGF-I replacement prevents and reverses part of these handicaps. Two 2024 review articles (identical text) discuss the molecular basis, clinical manifestations and therapeutic prospects of Laron syndrome but provide no new patient data.
What is still missing are prospective controlled trials comparing different IGF-I dosing regimens, long-term outcome data on cardiovascular and metabolic endpoints in treated versus untreated patients, and studies that stratify patients by age at treatment start, genotype, or baseline height deficit. The Indian case series are small and lack treatment follow-up. No trial has yet addressed whether early IGF-I therapy prevents the adult comorbidities described in the 76-patient cohort.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Hormone Research in Paediatrics · 1999 · 117 citations
Long-Term Treatment of Growth Hormone Insensitivity Syndrome with IGF-I
AbstractA total of 33 patients (17 female, 16 male) with Laron syndrome (n = 31) or hGH-1 gene (n = 2, type IA deletion) from 22 centres in 12 countries were enrolled in a study conducted by Pharmacia & Upjohn, Stockholm, which was designed to test the efficacy, in terms of growth promotion and safety, of IGF-I (Igef(TM)). The patients were treated with 40-120 microg/kg IGF-I s.c. twice daily after meals. After the study ended, the patients continued to be treated on an individual basis. The results of 17 patients, who were treated for 48 months or longer were available for the present analysis. Six patients were treated for up to 72 months. When treatment started, the mean age of these patients (8 female, 9 male) was 9.1 (3.7-13.5) years and mean height was -6.5 +/- 1.3 SDS. At the end of the observation period, the mean age of the 17 patients was 14.2 (9.1-17. 7) years and mean height was -4.9 +/- 1.9 SDS. All patients showed a significant increase in growth during the final year on IGF-I, with two of them reaching the age-corresponding 3rd centile. The total gain in height (DeltaHT) was 1.7 +/- 1.2 SDS. DeltaHT SDS correlated negatively with age at onset of treatment (R(2) = -0.78, p < 0.02). BMI was 0.6 +/- 1.8 SDS at start of treatment and 1.8 +/- 1.5 SDS at the end of observation. Total DeltaHT SDS correlated positively with total DeltaBMI SDS (R(2) = 0.59, p < 0.01). Long-term treatment of patients with GHIS thus proved to be effective in promoting growth. If treatment is started at an early age, there is considerable potential for achieving height normalisation. The treatment modalities need to be optimized with respect to the growth-promoting and metabolic effects of IFG-I.
Indian Journal of Endocrinology and Metabolism · 2014 · 17 citations · open access
Clinical features and endocrine profile of Laron syndrome in Indian children
AbstractINTRODUCTION: Patients with growth hormone (GH) insensitivity (also known as Laron syndome) have been reported from the Mediterranean region and Southern Eucador, with few case reports from India. We present here the clinical and endocrine profile of 9 children with Laron syndrome from India. MATERIAL AND METHODS: Nine children diagnosed with Laron syndrome based on clinical features of GH deficiency and biochemical profile suggestive of GH resistance were studied over a period of 5 years from January 2008 to January 2013. RESULTS AND DISCUSSION: Age of presentation was between 2.5-11.5 years. All children were considerably short on contemporary Indian charts with mean (SD) height Z score -5.2 (1.6). However, they were within ± 2 SD on Laron charts. No child was overweight [mean (SD) BMI Z score 0.92 (1.1)]. All children had characteristic facies of GH deficiency with an added feature of prominent eyes. Three boys had micropenis and 1 had unilateral undescended testis. All children had low IGF-1 (<5 percentile) and IGFP-3 (<0.1 percentile) with high basal and stimulated GH [Basal GH mean (SD) = 13.78 (12.75) ng/ml, 1-h stimulated GH mean (SD) = 46.29 (25.68) ng/ml]. All children showed poor response to IGF generation test. CONCLUSION: Laron syndrome should be suspected in children with clinical features of GH deficiency, high GH levels and low IGF-1/IGFBP-3. These children are in a state of GH resistance and need IGF-1 therapy.
Journal of Pediatric Endocrinology and Metabolism · 2004 · 9 citations
Classical Phenotype of Laron Syndrome in a Girl with a Heterozygous Mutation and Heterozygous Polymorphism of the Growth Hormone Receptor Gene
AbstractWe describe here a 19 month-old girl with classical Laron syndrome (LS). Molecular analysis of the GH receptor gene in the patient and her parents was performed. The patient was found to be heterozygous for a mutation in exon 4 (R43X) and heterozygous for a polymorphism in exon 6 (Gly168Gly). Her mother was also heterozygous for R43X but homozygous for the polymorphism. In the father, a heterozygous polymorphism was found. Contrary to previous assumptions that only homozygous patients express the typical phenotype, this patient shows all the classical features of LS, despite being a heterozygote for a pathological defect.
Journal of Pediatric Endocrinology and Diabetes · 2023 · 2 citations · open access
Laron syndrome in South Indian children – A descriptive study
AbstractObjectives: The objectives of this study were to describe the clinical and biochemical features of five children with Laron syndrome (LS) from South India. Material and Methods: This is a prospective descriptive case series of five children with clinical and biochemical features of LS managed over 5 years. Results: Five children (two girls and three boys) with LS with the mean age group of 5.9 ± 1.7 years and the mean age at diagnosis of 2.7 ± 0.8 years are described. All children were born out of consanguinity and all had typical phenotypic facies of LS. The mean Z-scores of height, weight, and body mass index on follow-up for the cohort were −7.0 ± 1.6, −5.9 ± 2.8, and −0.1 ± 0.7, respectively, and they were within ± 2 SD of the mean for children in LS chart. The median basal growth hormone level for age was 13 ng/mL and the median growth hormone levels at 30 min, 60 min, 90 min, and 120 min post-stimulation test were 35 ng/mL, 35 ng/mL, 44 ng/mL, and 50 ng/mL, respectively. All of them had insulin-like growth factor-1 (IGF-1) levels less than the 3 rd percentile and no increment during the IGF-1 generation test. The prevalence of micropenis was 100% and one child had symptomatic hypoglycemic episodes. Genetic analysis was performed in two boys and both harbored variants in the growth hormone receptor gene. Conclusion: LS should be suspected in children with clinical features of growth hormone deficiency along with elevated growth hormone levels and low IGF-1 levels with no increment of IGF-1 in the IGF-1 generation test.
Disabilities and Handicaps of Patients with Laron Syndrome
AbstractBackground: Laron Syndrome (LS) is a rare hereditary disease of dwarfism occurring with few exceptions in Jewish, Muslim and Asian populations or their descendants spread over all continents. It is caused by deletions or mutations in the GH-Receptor gene resulting in high serum levels of a structurally and biologically normal, but inactive GH and low to undetectable IGF-I. Aim: To summarize the disabilities and handicaps observed in patients with LS, from infancy through adult age. Results: Diagnosing, treating and following a cohort of 76 patients with LS, many since infancy into adult age, enabled our department to study not only their growth and social achievements, but also the difficulties these patients encounter in life. The longstanding IGF-I deficiency caused somatic and biochemical changes which lead to disabilities starting already in infancy and becoming more severe with advancing age. The most serious handicaps LS patients have are dwarfism, progressive obesity, diabetes, fatty liver, cardiovascular disease, neurological and orthopedic problems, leading to difficulties in vocational training, occupation and social life, all lowering the Quality of Life (QoL) of these patients. Conclusion: Early initiation of IGF-I replacement treatment of patients with Laron Syndrome prevents and reverses part of the handicaps of the longstanding IGF-I deficiency.
Zenodo (CERN European Organization for Nuclear Research) · 2024 · 0 citations · open access
Insights into Laron Syndrome: Unraveling the Molecular Basis, Clinical Manifestations, and Therapeutic Prospects
AbstractLaron Syndrome, a rare and intriguing genetic disorder, stands as a testament to the intricate interplay between genetics and endocrinology. This article delves into the comprehensive exploration of Laron Syndrome, elucidating its molecular underpinnings, intricate clinical presentations, and the evolving landscape of therapeutic interventions. By synthesizing current research and clinical observations, we aim to enhance the understanding of this syndrome, shedding light on the challenges posed by its unique pathophysiology. The exploration of growth hormone receptor insensitivity, molecular signaling cascades, and associated comorbidities will be discussed in detail, providing a foundation for future advancements in both diagnostic approaches and therapeutic strategies.
International Journal of Medical Science and Clinical Research Studies · 2024 · 0 citations · open access
Insights into Laron Syndrome: Unraveling the Molecular Basis, Clinical Manifestations, and Therapeutic Prospects
AbstractLaron Syndrome, a rare and intriguing genetic disorder, stands as a testament to the intricate interplay between genetics and endocrinology. This article delves into the comprehensive exploration of Laron Syndrome, elucidating its molecular underpinnings, intricate clinical presentations, and the evolving landscape of therapeutic interventions. By synthesizing current research and clinical observations, we aim to enhance the understanding of this syndrome, shedding light on the challenges posed by its unique pathophysiology. The exploration of growth hormone receptor insensitivity, molecular signaling cascades, and associated comorbidities will be discussed in detail, providing a foundation for future advancements in both diagnostic approaches and therapeutic strategies.
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.
