DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Duane-radial ray syndrome — 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 moduleDuane-radial ray syndrome 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 duane-radial ray 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.
What the evidence adds up to
A 2023 case report describes a family across four generations carrying a SALL4 nonsense variant (c.1717C>T, p.Arg573Ter). The proband, a boy born small for gestational age, had bilateral asymmetrical radial ray malformation (radial hypoplasia, ulnar flexure, bilateral thumb aplasia) and pelvic kidney dystopia, but no Duane anomaly, cardiac malformations, or ocular coloboma. At age 3.9 years he was found to have isolated growth hormone deficiency (stimulated GH 6.2 μg/L) with normal pituitary morphology on CT. He started growth hormone therapy at age 6.5 years (height 109 cm, −2.8 SDS) and by age 13 his height was 158.7 cm (−0.2 SDS). His father and paternal grandfather carried the same variant and had milder radial defects and short stature. The authors state this is the first report of isolated growth hormone deficiency in a SALL4-related disorder without midline brain anomalies.
Two surgical studies address Duane retraction syndrome as an ocular condition, not specifically in the context of SALL4 mutations. A 2008 retrospective study of 11 patients with Duane syndrome type I treated with recession of the medial rectus of the affected eye (4–7 mm) and contralateral medial rectus faden suture (13 mm) reported that after surgery 81.8% had no torticollis and the remainder had less than 10 degrees; all had postoperative esotropia under 5 prism dioptres. A 2017 retrospective review of 632 Duane syndrome charts identified 8 paediatric patients with type 2 (mean age 8.87 years, range 2–18). Four had amblyopia, four had abnormal head posture, all had exotropia (mean near deviation 24.75 PD, distance 29 PD). With refractive correction alone, 5 of 8 achieved orthotropia or less than 10 PD exotropia. Three underwent surgery; at final follow-up 6 of 8 had orthotropia or less than 10 PD exotropia.
No drug treatment is described in any of these abstracts. The 2023 case reports growth hormone replacement in one child with SALL4-related growth hormone deficiency, but this is hormone replacement for a proven deficiency, not a drug repurposing intervention. The surgical studies address strabismus and head posture, not the underlying genetic condition.
What remains missing is any trial of a pharmacological agent for Duane-radial ray syndrome itself. No drug has been tested in patients with SALL4 mutations to modify limb, kidney, or ocular development. The condition is rare, no patient registry with systematic outcome measures is described in these papers, and no funding for a drug-repurposing trial is mentioned. Stratification by SALL4 genotype and by specific organ involvement (ocular, renal, limb, pituitary) would be needed before any intervention could be assessed.
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 · 2023 · 9 citations
<i>SALL4</i> Phenotype in Four Generations of One Family: An Interplay of the Upper Limb, Kidneys, and the Pituitary
AbstractINTRODUCTION: The SALL4 gene encodes a transcription factor that is essential for early embryonic cellular differentiation of the epiblast and primitive endoderm. It is required for the development of neural tissue, kidney, heart, and limbs. Pathogenic SALL4 variants cause Duane-radial ray syndrome (Okihiro syndrome), acro-renal-ocular syndrome, and Holt-Oram syndrome. We report a family with vertical transmission of a SALL4 pathogenic variant leading to radial hypoplasia and kidney dystopia in several generations with additional growth hormone deficiency (GHD) in the proband. CASE PRESENTATION: Our male proband was born at the 39th week of gestation. He was born small for gestational age (SGA; birth weight 2,550 g, -2.2 SDS; length 47 cm, -2.0 SDS). He had bilateral asymmetrical radial ray malformation (consisting of radial hypoplasia, ulnar flexure, and bilateral aplasia of the thumb) and pelvic kidney dystopia, but no cardiac malformations, clubfoot, ocular coloboma, or Duane anomaly. He was examined for progressive short stature at the age of 3.9 years, where his IGF-1 was 68 μg/L (-1.0 SD), and growth hormone (GH) after stimulation 6.2 μg/L. Other pituitary hormones were normal. A brain CT revealed normal morphology of the cerebral midline and the pituitary. He had a dental anomaly - a central mandibular ectopic canine. MRI could not be done due to the presence of metal after multiple corrective plastic surgeries of his hands. His mother's and father's heights are 152.3 cm (-2.4 SD) and 177.8 cm (-0.4 SD), respectively. His father has a milder malformation of the forearm. The affected paternal grandfather (height 164 cm; -2.3 SD) has a radial ray defect with missing opposition of the thumb. The family reports a similar phenotype of radial dysplasia in the paternal grandfather's mother. The proband started GH therapy at age 6.5 years when his height was 109 cm (-2.8 SDS) and he experienced catch-up growth as expected in GHD. Puberty started spontaneously at the age of 12.5 years. At age 13, his height was 158.7 cm (-0.2 SDS). Whole-exome sequencing revealed a nonsense variant in the SALL4 gene c.1717C>T (p.Arg573Ter) in the proband, his father, and paternal grandfather. CONCLUSION: This is the first observation of a patient with a congenital upper limb defect due to a pathogenic SALL4 variant who has isolated GHD with no apparent cerebral or facial midline anomaly and has been successfully treated with growth hormone.
Archivos de la Sociedad Española de Oftalmología · 2008 · 7 citations · open access
Tratamiento quirúrgico del síndrome de duane, tipo I mediante retroinserción del recto medial del lado afecto y faden del recto medial contralateral
AbstractPURPOSE: Different surgical approaches have been described for the treatment of Duane's syndrome. The purpose of our study is to report the results of patients undergoing recession of the medial rectus (MR) muscle of the affected eye and placement of contralateral MR faden posterior fixation sutures. METHODS: Retrospective study of 11 patients treated by a 4-7 mm recession of the MR of the affected eye and 13 mm faden posterior fixation suture of the contralateral MR in order to correct abnormal head position and esotropia in primary position. RESULTS: After surgery, there was no torticolis in 81.8% of patients, with less than 10 degrees of torticolis in the remainder. In all patients, postoperative esotropia was less than 5 prismatic dioptres. CONCLUSION: This is a safe and effective procedure in Duane's syndrome type I to treat moderate esotropia and torticolis.
The clinical features and management of Duane’s retraction syndrome type 2 in pediatric patients
AbstractThe aim of this study was to describe the demographic details, features, and clinical management of pediatric patients with Duane retraction syndrome (DRS) type 2. Methods: A total of 632 charts from patients who were diagnosed with DRS between January 1998 and January 2016 were retrospectively reviewed. DRS type 2 patients who were <18 years old were identified. Demographic data and clinical findings from pediatric patients with a follow-up time >1 year were collected. Orthotropia or 10 prism diopters (PD) at near and distance fixation in primary position with available optical correction at the last visit was considered a satisfactory outcome. Results: There were 5 girls (62.5%) and 3 boys (37.5%). The average age at the first visit was 8.876.70 years (range: 2-18 years). The left eye was affected in 4 patients, the right eye in 3 patients, and 1 patient had bilateral involvement. Amblyopia was detected in 4 patients. Four patients had abnormal head posture (AHP). All of the patients had exotropia (XT). The near deviation angle was 24.7516.45 PD (range: 4-60 PD), and the distance deviation angle was 2923.12 PD (range: 10-80 PD). Orthotropia/<10 PD XT was seen in 5 patients with refractive correction. Three patients underwent surgery to correct deviation. In the final examination, 2 patients had AHP and orthophoria/<10 PD XT was observed in 6 patients. Conclusion: Amblyopia and deviation in primary position was common in children with DRS type 2 in our small group; therefore, detailed patient examinations are very important. Surgery would be appropriate for patients with strabismus and/or AHP.
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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