DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for achondrogenesis type II — 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 moduleAchondrogenesis type II 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 achondrogenesis type ii 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
collagen type II alpha 1 chain (COL2A1) — COL2A1 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 p33drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5NIR · 1.74 Å · ligand 3,6,9,12,15,18-HEXAOXAICOSANE-1,20-DIOL (P33). Experimental structure, not a prediction.
What the evidence adds up to
Achondrogenesis type II (Langer-Saldino) is a lethal skeletal dysplasia caused by dominant mutations in the COL2A1 gene. One 2007 report described four pregnancies in a family where the father carried a mosaic COL2A1 mutation (10370G>T, G346V). The first child died neonatally; the second and third fetuses showed short limbs and fetal hygroma at 17 weeks, and after termination had findings consistent with achondrogenesis type II. The fourth pregnancy showed fetal hydrops and a septated cystic hygroma at 11 weeks, and chorionic villus sampling confirmed the same mutation. A 2019 case report identified a novel heterozygous missense variant, c.2546G>A (p.Gly849Asp), in a newborn admitted to a neonatal intensive care unit with extremely short extremities, a small chest, abdominal distension, and respiratory distress.
A 1981 review distinguished type II from type I achondrogenesis by noting fewer stillbirths, longer gestation and survival time, larger body size, longer limbs, and characteristic craniofacial features. Both infants described in that report died neonatally. The 2019 case report states that achondrogenesis occurs in approximately one in every 40,000–60,000 newborns and that type II is typically characterised by short arms and legs, a small chest with short ribs, lung hypoplasia, a prominent forehead, a small chin, an enlarged abdomen, and possible polyhydramnios and hydrops.
A separate 2019 paper on achondrogenesis type IA (Houston-Harris) reported a family with four affected products from six previous pregnancies. Statistical analysis of that family and at least four previously described families showed significant differences between expected and observed numbers of affected members, which the authors considered incongruent with the autosomal recessive inheritance previously reported for type IA. They proposed a new subtype of achondrogenesis type IA due to a preferential germline mutation.
No treatment or intervention for achondrogenesis type II appears in these abstracts. What remains missing is any clinical trial, any attempt at prenatal or postnatal therapy, and any systematic patient registry that could stratify cases by specific COL2A1 mutation to see whether the few reported longer survivals are linked to particular genotypes.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
American Journal of Medical Genetics · 1981 · 43 citations
Achondrogenesis: A review with special consideration of achondrogenesis type II (langer‐saldino)
AbstractWe describe two dwarfed infants with large head, short neck and chest, prominent abdomen, and short limbs. Both died neonatally. Radiographic and morphologic characteristics identified the Langer-Saldino form of achondrogenesis (type II). Review of type II achondrogenesis documented distinctive clinical and anthropometric manifestations (fewer stillbirths, longer survival time and gestation period, larger size of the baby, longer limbs, and characteristic craniofacial features) as compared with type I achondrogenesis (Parenti-Fraccaro).
American Journal of Medical Genetics Part A · 2007 · 33 citations
A familial case of achondrogenesis type II caused by a dominant <i>COL2A1</i> mutation and “patchy” expression in the mosaic father
AbstractAchondrogenesis type II (ACG2) is the most severe disorder that can be produced by dominant mutations in COL2A1. We report on four pregnancies of an apparently healthy, nonconsanguineous young couple. The father had scoliosis as a child, and has slight body disproportion with short trunk. The first child was born at 32 weeks and died neonatally. In the second pregnancy, short limbs and fetal hygroma were noted on ultrasound at 17 weeks' gestation. Similar findings were observed in the third fetus. Clinical, radiological, and histological evaluation of the fetuses after termination of the pregnancies showed findings consistent with ACG2. Molecular analysis of genomic DNA extracted from amniotic cells of the second and third fetuses revealed heterozygosity for a 10370G > T missense mutation (G346V) in the COL2A1 gene. This mutation was also found in the father, as a mosaic. The couple had a fourth pregnancy, and at 11 weeks fetal hydrops with a septated cystic hygroma were obvious. DNA from CVS demonstrated the same COL2A1 mutation.
Balkan Journal of Medical Genetics · 2019 · 4 citations · open access
Achondrogenesis type 2 in a newborn with a novel mutation on the <i>COL2A1</i> gene
AbstractAbstract Achondrogenesis is a group of rare and fatal disorders occurring in approximately one in every 40,000-60,000 newborns. Achondrogenesis is classified in three groups, as Achondrogenesis type 1A (Houston-Harris type or AC-G1A), Achondrogenesis type 1B (Parenti-Fraccaro type or ACG1B) and Achondrogenesis type 2 (Langer-Saldino type or ACG2), depending on clinical and radiological findings. Achondrogenesis Type 2 is a lethal skeletal dysplasia that is typically characterized by short arms and legs, a small chest with short ribs, lung hypoplasia, a prominent forehead, a small chin, and an enlarged abdomen that may accompanied by polydramnios and hydrops. This study contributes to the literature by presenting a patient who was admitted to the Level ΙΙΙ Neonatal Intensive Care Unit (NICU), Bursa, Turkey), with extremely short extremities, a small chest, abdominal distention and respiratory distress, who was diagnosed with ACG2. On the COL2A1 gene, genetic analysis with next generation sequencing (NGS), was revealed to have a heterozygous missense variation, c.2546G>A, p.Gly849Asp mutation, which is a different genetic variant that has not been previously described in the literature.
Cirugía y Cirujanos (English Edition) · 2019 · 2 citations · open access
New subtype of familial achondrogenesis type IA (Houston-Harris)
AbstractBackground: Achondrogenesis is a skeletal dysplasia characterized primarily by short stature, severe micromelia, short and narrow chest, prematurity, polyhydramnios, fetal hydrops, and in utero or neonatal death. Based on the radiological and histopathological findings, there are three types of achondrogenesis: type 1A (Houston-Harris), type 1B (Fraccaro) and type 2 (Langer-Saldino). Clinical case: A premature female product was studied whose clinical, radiological and histopathological characteristics were compatible with achondrogenesis Type 1A. The family information allowed us to conclude that the 4 products of the 6 previous pregnancies were affected. Statistical analysis in at least 4 families previously described, including this family case showed significant differences between expected and observed number of members, being incongruent with an autosomal recessive mode of inheritance previously reported. Conclusions: therefore, it could be considered a new subtype of achondrogenesis type 1A due to the presence of a preferential germline mutation.
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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