Rare & Orphan Lab · DeCure for X
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for acromesomelic dysplasia 1, Maroteaux type — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
No approved-drug candidate for acromesomelic dysplasia 1, maroteaux type 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.
Indian hedgehog signaling molecule (IHH) — IHH 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.
RCSB Protein Data Bank · entry 3K7J · 1.9 Å · ligand CARBONATE ION (CO3). Experimental structure, not a prediction.
Acromesomelic dysplasia Maroteaux type is an autosomal recessive skeletal disorder caused by mutations in the NPR2 gene on chromosome 9p21-p12, which encodes the natriuretic peptide receptor B. The condition results in extremely short stature with disproportionate shortening of the middle and distal segments of the limbs. A 1980 summary of radiographic features states that diagnosis is possible in affected individuals over six months of age. A 2015 study of three consanguineous families identified two novel missense variants (p.Arg601Ser; p.Arg749Trp) and one previously reported splice site variant (c.2986+2T>G) in the NPR2 gene.
A 2024 case report describes an 11-year-old girl with compound heterozygous pathogenic NPR2 variants, a height of 108.5 cm (standard deviation score -5.03), and a weight of 23.3 kg (SDS -2.74). Her parents were not consanguineous but had short stature (father 154 cm, SDS -3.16; mother 148 cm, SDS -2.36). She had a disproportionate body proportion with an upper-to-lower segment ratio of 1.25, shortened radius, ulna, tibia, and fibula, and short broad metacarpals and phalanges with cone-shaped epiphyses. An insulin tolerance test showed peak growth hormone of 8.4 ng/ml and peak cortisol of 586 nmol/L, which the authors interpreted as isolated severe growth hormone deficiency. Bone age was indeterminate due to abnormal epiphyses. The authors note that average adult height in this condition is estimated to be less than 120 cm, and that no published data show a relationship between acromesomelic dysplasia Maroteaux type and growth hormone deficiency. They cite literature reporting that three children with the condition who received high-dose growth hormone treatment (0.05–0.1 mg/kg/day) had positive effects on height.
No controlled trial of any drug for this condition has been reported. What is missing is a prospective study with a defined dosing regimen, a control group, and objective height endpoints, as well as any investigation of whether patient genotype or growth hormone status predicts response.
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
AbstractThe radiographic features of acromesomelic dysplasia are presented, along with a summary of pertinent clinical features. They are thought to allow a diagnosis in affected individuals over six months of age. Since the condition has an autosomal recessive mode of genetic transmission and results in extremely short stature, the establishment of the diagnosis has practical importance.
https://doi.org/10.1148/radiology.137.2.7433666AbstractAcromesomelic dysplasia Maroteaux type (AMDM) is an autosomal recessive skeletal disorder characterized by disproportionate short stature with shortening of the acromesomelic sections of the limbs. AMDM is caused by mutations in the NPR2 gene located on chromosome 9p21-p12. The gene encodes the natriuretic peptide receptor B (NPR-B) that acts as an endogenous receptor for C-type natriuretic peptide (CNP). Both CNP and NPR-B are considered as important regulators of longitudinal growth. The study presented here investigated three consanguineous families (A, B, C) segregating AMDM in an autosomal recessive manner. Linkage in the families was established to the NPR2 gene on chromosome 9p12-21. Sequence analysis of the gene revealed two novel missense variants (p.Arg601Ser; p.Arg749Trp) in two families and a previously reported splice site variant (c.2986+2T>G) in the third family.
https://doi.org/10.1111/ahg.12116AbstractINTRODUCTION/BACKGROUNDAcromesomelic dysplasia, type Maroteaux (AMDM) is a rare skeletal dysplasia, characterized by severe disproportionate short stature, primarily affecting the middle and distal segments of the limbs. CASEAn 11-year-old female presented with extremely short stature. She was born with a birth weight of 2.6 kg and has been noticed to be short since 2 years old. Her parents were not consanguineous but had a strong family history of short stature. Father’s height was 154 cm (SDS -3.16) and mother’s height was 148 cm (SDS -2.36). The girl has normal intelligence and an unremarkable medical history. She was prepubertal and markedly short with a height of 108.5 cm (SDS -5.03) and a weight of 23.3 kg (SDS - 2.74). Her height was 3 SD below her mid-parental height (MPH SDS-2.3). She had a disproportionate body proportion with an upper segment to lower body segment ratio of 1.25 and shortened middle and distal segments of the limbs. Skeletal survey showed shortening of the radius, ulna, tibia, and fibula as well as short and broad metacarpals and phalanges, with cone-shaped epiphyses. She had an insulin tolerance test that showed peak growth hormone of 8.4 ng/ml and peak cortisol of 586 nmol/L (normal), which suggested isolated severe growth hormone deficiency. Bone age was indeterminate due to abnormal epiphyses. Whole exome sequencing identified compound heterozygous pathogenic variants in NPR2 which is associated with autosomal recessive AMDM. We did not proceed with the 2nd GH test since the genetic results were confirmative. CONCLUSIONWe described a child with AMDM and severe growth hormone deficiency. Average adult height is estimated to be less than 120 cm. No published data showed that ADMD is related to GHD. Literature reviews showed that 3 AMDM children who received high-dose growth hormone treatment (0.05- 0.1 mg/kg/day) had positive effects on height improvements.
https://doi.org/10.15605/jafes.039.s1.237AbstractThis chapter discusses acromesomelic and acromelic dysplasias/dysostoses and related disorders and includes discussion on acromesomelic dysplasias (Maroteaux type), Grebe dysplasia, brachydactyly A1, brachydactyly B, brachydactyly C, brachydactyly D, brachydactyly E, brachydactyly (Christian type), tricho-rhino-phalangeal dysplasia (type 1), tricho-rhino-phalangeal dysplasia (type 2), acrocapitofemoral dysplasia, Albright hereditary osteodystrophy, acrodysostosis, geleophysic dysplasia, acromicric dysplasia, Myhre syndrome, and SOFT syndrome. Each discussion includes major radiographic features, major clinical findings, genetics, major differential diagnoses, and a bibliography.
https://doi.org/10.1093/med/9780190626655.003.0013Disease 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.
