DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for mulibrey nanism — 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.
Disease moduleMulibrey nanism maps to a 3-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 mulibrey nanism 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
tripartite motif containing 37 (TRIM37) — TRIM37 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 3LRQ · 2.292 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Mulibrey nanism is a rare autosomal recessive disorder caused by mutations in the TRIM37 gene, which encodes a RING finger ubiquitin E3 ligase. The condition is characterised by severe pre- and postnatal growth failure, constrictive pericarditis (present in about 20% of patients), deregulation of glucose and lipid metabolism including type 2 diabetes, fatty liver, and hypertension, and an increased risk for tumours. More than 80% of previously reported patients are of Finnish origin with a founder mutation, but cases have been described elsewhere: an Australian patient carried two novel mutations (p.Cys109Ser B-box missense and p.Glu271_Ser287del in-frame deletion), and a Turkish boy had a homozygous two base pair deletion (c.1894_1895delGA). Wilms' tumour has been reported in an Australian patient, and ultrasound surveillance for Wilms' tumour is recommended for children with the condition.
The TRIM37 protein localises at least partially to peroxisomes and possesses E3 ubiquitin ligase activity, implying defective proteasomal degradation or regulatory ubiquitination as possible pathogenetic mechanisms. However, the exact physiological function of TRIM37 and the molecular mechanisms underlying mulibrey nanism remain unsolved. In non-mulibrey patients with cancer, a wide variety of cancers are associated with overexpression of TRIM37, suggesting that normal cells need an optimal equilibrium in TRIM37 expression.
One case report describes a 22-year-old Czech patient with mass ascites as the main clinical finding. Combined treatment with spironolactone and furosemide improved quality of life and allowed conservative management of ascites without repeated punctures, but the patient had multiple organ impairment, especially cardiac, and various complications were considered probable.
No drug has been tested in a clinical trial for mulibrey nanism. The idea that finding a way to keep TRIM37 expression in balance could lead to potential drugs remains speculative. What is missing is any funded preclinical or clinical drug development programme, a clear strategy for patient stratification given the rarity of the disorder, and a trial design that could accommodate the small number of patients worldwide.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
International Journal of Molecular Sciences · 2018 · 62 citations · open access
TRIMming down to TRIM37: Relevance to Inflammation, Cardiovascular Disorders, and Cancer in MULIBREY Nanism
AbstractTRIpartite motif (TRIM) proteins are part of the largest subfamilies of E3 ligases that mediate the transfer of ubiquitin to substrate target proteins. In this review, we focus on TRIM37 in the normal cell and in pathological conditions, with an emphasis on the MULIBREY (MUscle-LIver-BRain-EYe) genetic disorder caused by TRIM37 mutations. TRIM37 is characterized by the presence of a RING domain, B-box motifs, and a coiled-coil region, and its C-terminal part includes the MATH domain specific to TRIM37. MULIBREY nanism is a rare autosomal recessive caused by TRIM37 mutations and characterized by severe pre- and postnatal growth failure. Constrictive pericarditis is the most serious anomaly of the disease and is present in about 20% of patients. The patients have a deregulation of glucose and lipid metabolism, including type 2 diabetes, fatty liver, and hypertension. Puzzlingly, MULIBREY patients, deficient for TRIM37, are plagued with numerous tumors. Among non-MULIBREY patients affected by cancer, a wide variety of cancers are associated with an overexpression of TRIM37. This suggests that normal cells need an optimal equilibrium in TRIM37 expression. Finding a way to keep that balance could lead to potential innovative drugs for MULIBREY nanism, including heart condition and carcinogenesis treatment.
Wilms’ tumor and novel <i>TRIM37</i> mutations in an Australian patient with mulibrey nanism
AbstractMulibrey nanism is a rare autosomal recessive growth disorder with prenatal onset, including occasional progressive cardiopathy, characteristic facial features, failure of sexual maturation, insulin resistance with type 2 diabetes, and an increased risk for Wilms' tumor. Mulibrey nanism is prevalent in the Finnish population and appears extremely rare elsewhere. However, cases outside of Finland may be underdiagnosed or misdiagnosed as having the 3-M or Silver-Russell syndrome, two important differential diagnostic disorders. Here, we report the first Australian patient with mulibrey nanism, in whom the occurrence of Wilms' tumor suggested the correct diagnosis. This was confirmed by the identification of two novel mutations in tripartite motif protein 37 (TRIM37) encoding a RING finger ubiquitin E3 ligase. Both mutations, the p.Cys109Ser B-box missense mutation and the p.Glu271_Ser287del in-frame deletion in the tumor necrosis factor receptor associated factor (TRAF) domain alter the subcellular localization of TRIM37. As both the B-box and the TRAF domains are predicted to be important for mediating the protein-protein interactions, these mutations may help the understanding of the cellular interactions of TRIM37. Our findings imply the importance of early molecular diagnostics in cases of suspected mulibrey nanism and of identifying novel mutations with potential relevance for unraveling the underlying molecular pathology. Ultrasound surveillance for Wilms' tumor is recommended for children with mulibrey nanism.
A novel mutation in TRIM37 is associated with mulibrey nanism in a Turkish boy
AbstractMulibrey nanism is a rare autosomal-recessive disorder characterized by prenatal onset severe growth retardation and pericardial constriction associated with abnormalities of muscle, liver, brain and eye. More than 80% of previously reported patients are of Finnish origin in whom a founder mutation in the TRIM37 gene have been described. We report on a 7-year-old Turkish boy who presented with classical phenotypic features of mulibrey nanism. Mutation screening of the TRIM37 gene revealed that the proband had a homozygous two base pair deletion, c.1894_1895delGA, resulting in a frame-shift and a premature termination codon. Our proband is one of the rare examples of mulibrey nanism outside Finland and extends the mutation spectrum in this disorder.
Journal of Pediatric Endocrinology and Metabolism · 2010 · 1 citations
Mass Ascites in Mulibrey Nanism
AbstractMulibrey nanism is a rare inherited disease characterized by growth failure and multi-organ manifestations. Mulibrey nanism is extremely rare in the Czech Republic,only this one patient has been reported yet. Mass ascites was the main clinical finding in this 22-year-old male patient. Combined treatment with spironolactone and furosemide improved significantly the patients quality of life and allowed conservative treatment of ascites with no need of repeated punctures. Current clinical status of the patient was satisfactory but various complications in the future are very probable because this patient has multiple organs, especially cardial, impairment.
Oxford University Press eBooks · 2016 · 0 citations
TRIM37 and Mulibrey Nanism
AbstractAbstract Mulibrey nanism is an autosomal recessive inherited rare prenatal-onset growth restriction disorder with multiorgan manifestations. Main features include progressive cardiopathy, characteristic dysmorphic features, insulin resistance, metabolic syndrome, increased risk for tumors and infertility due to gonadal failure. The identification of mutations in the TRIM37 gene as the underlying primary defect has enabled molecular diagnostics of mulibrey nanism. The TRIM37 protein has been shown to localize, at least partially, to the peroxisomes and to possess E3 ubiquitine ligase activity, implying defective proteasomal degradation or regulatory ubiquitination as possible pathogenetic mechanisms for mulibrey nanism. However, the exact physiological function of TRIM37 and the molecular mechanisms underlying mulibrey nanism still remain unsolved.
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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