DeCure's autonomous Metabolic AI scientist is researching a drug-repurposing hypothesis for lysosomal acid lipase deficiency — 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 moduleLysosomal acid lipase deficiency 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 lysosomal acid lipase deficiency 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
Lysosomal acid lipase deficiency is a rare hereditary enzymopathy with two phenotypic forms: Wolman disease and cholesterol ester storage disease. The condition is characterised by an alteration of lipid metabolism that generates deposits of cholesterol and triglyceride esters in the body. Clinical presentation depends on the level of residual enzymatic activity. A 1998 case series of three unrelated patients reported that the deficiency can present with highly heterogeneous signs and symptoms, and it should be considered in children presenting with gastrointestinal symptoms associated with dyslipidemia. That series described a rare variant that may suggest a Brazilian genotype for the deficiency.
The 2019 review states that lysosomal acid lipase deficiency has low prevalence and high morbidity and mortality in both children and adults. It notes that a recombinant enzyme is available which can improve lipid and liver parameters as well as disease progression. The review emphasises that timely diagnosis is imperative for prevention of morbidity and mortality. The 2023 clinical guidelines provide evidence-based recommendations for management of children with the deficiency, focusing on differential diagnostic search and the two phenotypic forms.
The ARISE trial (NCT01757184) was a randomised, double-blind, placebo-controlled phase 3 study designed to evaluate sebelipase alfa in patients with lysosomal acid lipase deficiency. The article title reports that sebelipase alfa normalised ALT and multiple other disease-related abnormalities. No numerical data from the trial (such as sample size, survival, or response rates) are provided in the abstracts given.
What is still missing is the full numerical results from the phase 3 trial, including the number of patients enrolled, the magnitude of biochemical improvements, and any effect on clinical endpoints such as survival or progression to cirrhosis. The abstracts do not specify how patient stratification by phenotypic form (Wolman disease versus cholesterol ester storage disease) or by age affects treatment response. No cost or access data for the recombinant enzyme are mentioned.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Jornal de Pediatria · 1998 · 15 citations
Objectifs et paradigmes d'enseignement/apprentissage
AbstractThis case series supports that lysosomal acid lipase deficiency can present with highly heterogeneous signs and symptoms among patients, but it should be considered in children presenting with gastrointestinal symptoms associated with dyslipidemia. We describe a rare variant in three non-related patients that may suggest a Brazilian genotype for lysosomal acid lipase deficiency.
Gaceta Médica de México · 2019 · 1 citations · open access
Deficiencia de lipasa ácida lisosomal, una patología infrecuente
AbstractLysosomal acid lipase deficiency is a genetic disease with a low prevalence and high morbidity and mortality in children and adults. It is characterized by an alteration of lipid metabolism, which generates cholesterol and triglyceride esters deposits in the body. Its clinical presentation depends on enzymatic activity. This condition should be suspected in patients with lipid or liver alterations after ruling out other diagnoses. Currently, there is the option of using a recombinant enzyme, which can improve lipid and liver parameters, as well as disease progression. Establishing a timely diagnosis in order to initiate specific treatment early is imperative for the prevention of morbidity and mortality. The purpose of this work is to perform a review of the literature about lysosomal acid lipase deficiency and to guide about its pathophysiology, clinical manifestations, diagnosis and treatment.
Педиатрическая фармакология · 2023 · 1 citations · open access
Clinical guidelines for the management of children with lysosomal acid lipase deficiency
AbstractLysosomal acid lipase deficiency is s a rare hereditary enzymopathy. The article presents epidemiological data and features of etiopathogenesis of two phenotypic forms of lysosomal acid lipase deficiency — Wolman disease and cholesterol ester storage disease. Special attention has been given to the key issues of differential diagnostic search, clinical guidelines based on the principles of evidence-based medicine have been given.
Sebelipase Alfa Normalizes ALT and Multiple other Disease-Related Abnormalities in Patients with LAL-D
AbstractLysosomal acid lipase deficiency (LAL-D) is an autosomal genetic recessive disorder that leads to an inability to break down lipid particles in the lysosome, and it is associated with early-onset cirrhosis and cardiovascular disease. This article discusses the Acid Lipase Replacement Investigating Safety and Efficacy trial [ARISE; NCT01757184] was a randomized, double-blind, placebo-controlled phase 3 study designed to evaluate sebelipase alfa in patients with LAL-D.
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.
