DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Wolman disease — 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 moduleWolman disease 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 wolman disease 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
lipase A, lysosomal acid type (LIPA) — LIPA 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 6V7N · 2.62 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Wolman disease is a rare autosomal recessive disorder caused by mutations in the LIPA gene, which encodes lysosomal acid lipase. In two unrelated Bulgarian families, Sanger sequencing identified two different homozygous mutations: a missense mutation c.260G > T (p.Gly87Val) affecting the enzyme active site, and a splice-site change c.822+1G > A that probably destroys the enzyme polypeptide chain. Both mutations produced a very similar phenotype involving liver, kidney, gastrointestinal, muscle and blood disturbances. Selective screening in two presumable endemic regions in Bulgaria found a carrier frequency of about 1% (1/100 newborns) for p.Gly87Val and 2% (2/100 newborns) for c.822+1G > A, indicating a recurrence risk of about 1:10000 in those regions.
A 2022 case report describes a 4.5-month-old boy with fever, icterus and hepatosplenomegaly who was treated for presumed hemophagocytic lymphohistiocytosis (HLH). Genetic analysis after his death revealed a novel LIPA gene mutation: exon 4 c.G353A (p.G118D), converting glycine to aspartic acid. The authors note that the presentations of Wolman disease and HLH can resemble each other, and that several case reports describe patients with Wolman disease initially diagnosed as HLH.
A separate report of two brothers with Wolman disease treated with hematopoietic stem cell transplantation (HSCT) states that both died from hepatic complications. The authors note that only three cases of successful treatment by HSCT had been reported at that time, and that the two brothers exemplify the obstacles to successful HSCT in this disease.
What is still missing is a reliably effective treatment. HSCT has failed in multiple cases, and no other therapy has shown consistent success in the published literature. The diagnosis itself remains difficult because Wolman disease can mimic HLH, and novel mutations continue to be identified only after death. No large, prospective trial of any intervention has been conducted, and patient numbers are extremely small.
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 Molecular Biology · 2017 · 2 citations · open access
Wolman Disease in Bulgarian Patients: Selective Genetic Screening in Two Presumable Endemic Regions
AbstractWolman disease is a rare autosomal recessive disorder caused by mutations in the LIPA gene (10q23.31). The LIPA gene encodes lysosomal acid lipase (LAL), which plays a key role in hydrolysis of the cholesteryl esters and triglycerides. Two unrelated families from Bulgaria were referred for genetic testing with clinical diagnosis Wolman disease. Sanger sequencing of all coding exons and exon-intron boundaries of the LIPA gene was performed. The index patients were found to be homozygous for two different mutations in the LIPA gene: a missense mutation, c.260G > T, p.Gly87Val, which affects the enzyme active site and a splice-site change, c.822+1G > A, which most probably destroys the enzyme polypeptide chain. These two completely different types of mutations along the LIPA gene resulted in a very similar phenotype involving liver, kidney, gastrointestinal, muscle and blood disturbances. As consanguinity is not typical for the Bulgarian population, a possible explanation of the homozygosity could be presence of endemic regions for given mutations. To check this hypothesis, selective screening for these mutations was performed in two presumable endemic regions in Bulgaria. Altogether, 100 newborns were screened for p.Gly87Val mutation and the detected carrier frequency was about 1% (1/100), while in the group of 100 newborns screened for the c.822 + 1G > A mutation the detected carrier frequency was 2% (2/100). The results indicate a high recurrence risk of Wolman disease in these particular Bulgarian regions of about 1:10000. These findings are from crucial importance for the inhabitants of the corresponding parts of Bulgaria. They may benefit from early genetic testing and adequate genetic counselling during family planning.
Al-Basit: Revista de estudios albacetenses · 1980 · 1 citations
In memoriam: Tomás Navarro Tomás
AbstractWolman disease (WD) is a fatal storage disease caused by the deficiency of the lysosomal enzyme acid lipase. Only 3 cases of successful treatment by hematopoietic stem cell transplantation (HSCT), are reported. We report a case of two brothers with WD who were treated with HSCT, but both died from hepatic complications. Together they exemplify the obstacles to successful HSCT in WD. We suggest that different strategies should be investigated in order to offer treatment for this disease.
Research Square · 2022 · 0 citations · open access
Wolman Disease Presenting With HLH Syndrome and a Novel LIPA Gene Variant: a Case-based Review
AbstractAbstract Introduction: Wolman Disease (WD) is a rare disease caused by the absence of functional liposomal acid lipase (LAL) due to mutations in LIPA gene. It presents with organomegaly, malabsorption and adrenal calcifications. The presentations can resemble Hemophagocytic lymphohistiocytosis (HLH), the life threatening hyper-inflammatory disorder. Method: We present a 4.5-month-old boy with fever, icterus and hepatosplenomegaly who was treated according to presumed HLH disease. There are some case reports in the literature presenting patients with WD primarily diagnosed as HLH, which we discussed in this review. Results: The genetic analysis revealed after his demise was compatible with WD, introducing a novel mutation in LIPA gene: exon 4: NM_001127605: c. G353A (p.G118D), which converts the Glycine amino acid to Aspartic acid. Conclusions: Considering the similarities in presentation of WD and HLH, the patient’s life can be saved if special attention is paid to presenting features of a patient with suspected HLH, i.e., symptoms, finding on physical exams, laboratory values and radiologic findings, and the proper treatment is urgently initiated. Reporting the novel mutations of WD can help geneticists interpret the results of their patients’ genetic studies appropriately, leading to correct diagnosis and treatment.
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.
