DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for familial lipoprotein lipase deficiency — screening already-approved drugs against its 38-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleFamilial lipoprotein lipase deficiency maps to a 38-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 familial lipoprotein 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
ABO, alpha 1-3-N-acetylgalactosaminyltransferase and alpha 1-3-galactosyltransferase (ABO) — ABO 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 6-deoxy-alpha-l-galactopyranosyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4Y63 · 1.3 Å · ligand octyl 2-O-(6-deoxy-alpha-L-galactopyranosyl)-beta-D-galactopyranoside (BHE). Experimental structure, not a prediction.
What the evidence adds up to
Familial lipoprotein lipase deficiency, also called familial chylomicronemia syndrome, is an autosomal recessive disorder caused by loss-of-function mutations in the lipoprotein lipase gene. Patients have severe hypertriglyceridaemia above 2000 mg/dL. A 2024 report describes a 15-month-old boy with repeated pancreatitis episodes caused by this condition; genetic analysis found a novel homozygous mutation, c.626T>G; p.(Leu209*), classified as type 4 and likely pathogenic. A 2017 qualitative study of three patients with lipoprotein lipase deficiency found that health-related quality of life, measured by the EQ-5D-3L, was poor during acute attacks of pancreatitis but minimally impacted at interview. Patients reported fear, anxiety, depression, and frustration during and after hospitalisations, and the disease affected diet, socialising, relationships, college, work, and finances.
Treatment aims to lower triglycerides through a low-fat diet of less than 20 grams per day, supplemented with medium chain triglyceride fat to maintain caloric intake. In 2019, volanesorsen was approved by the European Medicines Agency as an adjunct treatment for adult patients with genetically proven familial chylomicronemia syndrome who have persisting episodes of pancreatitis despite diet. Alipogen tiparvovec, a gene therapy containing genetic material for lipoprotein lipase deficiency, showed efficacy in clinical trials, but the period during which the drug proved effective was rather short. The European Medicines Agency still permitted its clinical use.
One abstract discusses lysosomal acid lipase deficiency, a different disease that can mimic familial hypercholesterolemia, not familial lipoprotein lipase deficiency. Another abstract reviews familial hypercholesterolemia generally and does not address lipoprotein lipase deficiency. What remains missing is long-term data on volanesorsen and alipogen tiparvovec, including how well they prevent pancreatitis over years, and whether the short duration of effect for the gene therapy can be overcome. No trial has adequately stratified patients by mutation type or age of onset to guide treatment timing.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Педиатрическая фармакология · 2016 · 20 citations · open access
Deficiency of Lysosomic Acid Lipase: Clinical Recommendations for Child Health Care Delivery
AbstractThe deficiency of lysosomic acid lipase is a rare hereditary enzymopathy. The focus of this article is the present condition of this issue. The authors demonstrate epidemiological data and etiopathogenetic features of two phenotypic forms of lysosomic acid lipase deficiency -Wolman disease and cholesterol ester storage disease. Clinical features of both -the rapidly progressing form and the slowly developing cholesterol ester storage disease -are described in detail in this article. The algorithm and crucial steps of differential diagnosis are described in detail. Also, indications to pathogenetic therapy are carefully formulated, and the tactic of enzyme replacing therapy is given. The modern approaches to the management of child patients are described.
JACC Case Reports · 2023 · 5 citations · open access
Distinguishing Lysosomal Acid Lipase Deficiency From Familial Hypercholesterolemia
AbstractLysosomal acid lipase deficiency (LAL-D) is underrecognized because it manifests clinically with lipid and lipoprotein values similar to those observed in heterozygous familial hypercholesterolemia (FH). Although LAL-D is uncommon, understanding the differences between the 2 diseases has significant management implications. We present a case of LAL-D that masqueraded as FH. (Level of Difficulty: Advanced.)
The impact of lipoprotein lipase deficiency on health-related quality of life: a detailed, structured, qualitative study
AbstractAbstract Background Lipoprotein lipase deficiency (LPLD) is an autosomal recessive inherited disorder caused by loss-of-function mutations in genes involved in the lipoprotein lipase pathway. It is characterised by chylomicronaemia, severe hypertriglyceridaemia and an increased risk of recurrent pancreatitis that often requires hospitalisation. This research aimed to improve our understanding of the debilitating impact that LPLD has on the daily lives of patients and their families. Methods The research comprised a 2-h interview with the patient and, where possible, a 1-h interview with a family member; a 1-week pre- and post-interview task (written and/or video diary); and a 30â 45-min follow-up telephone interview. Feelings and thoughts at each stage of the disease journey were captured on a 0â 10 rating scale, while the impact of disease on overall health status was measured via the EuroQoL 5 domains, 3 levels (EQ-5D-3L) questionnaire (descriptive and visual analogue scale). Results Of four patients identified, three (two female, one male) were recruited to participate in the study; the male patient did not complete the pre-interview task or consent to a family member interview. Demographics and medical history differed among patients in terms of age at symptom onset, their journey to LPLD diagnosis, treatments, the number of attacks of pancreatitis and lengths of hospitalisations. Health-related quality of life, assessed by the EQ-5D-3L, was poor during acute attacks of pancreatitis but was minimally impacted by their condition at interview. Patients described feeling apprehensive, frightened, anxious, depressed or frustrated during and after hospitalisations; spouses of the two female patients also reported being worried or afraid. LPLD affected many aspects of daily living, including diet; socialising and building relationships; state of mind (fear of another attack of pancreatitis or lack of disease control); college and working life (through absenteeism and consequent financial implications); and being reliant on family and friends for support. Conclusions The interviews of the three patients with LPLD highlighted several concerns and emphasised the need for improved education, support, dietary advice and appropriate disease management. Additional support services would ease the fear and uncertainty surrounding attacks of pancreatitis, and would allow for improved treatment during hospitalisations.
Ведомости Научного центра экспертизы средств медицинского применения · 2015 · 0 citations
Алипоген типарвовек: долгая дорога к оценке отношения пользы и риска генотерапевтического препарата
AbstractAccording to EMA, advanced therapy medicinal products include, inter alia, therapeutic systems containing nucleic acids used for replacement or repair of genetic defects. Alipogen tiparvovec, a medicine containing genetic material for treatment of hereditary deficiency of lipoprotein lipase, meets these criteria. The article summarizes pathophysiological principles of this medicine action in subjects with lipoprotein lipase deficiency. The article describes the results of preclinical research conducted in mice and cats. Clinical trials revealed its efficiency in patients with hereditary lipoprotein lipase deficiency, however the period during which the drug proved efficient was rather short. Nevertheless the data obtained from alipogen tiparvovec clinical trials were convincing enough for EMA to permit its application in clinical practice.
DOAJ (DOAJ: Directory of Open Access Journals) · 2023 · 0 citations · open access
Familial Hypercholesterolemia
AbstractFamilial hypercholesterolemia (FH) is a group of autosomal co-dominant genetic diseases mainly characterized by abnormal low-density lipoprotein related metabolism. It is one of the most common inherited diseases in children and one of the most serious lipid metabolism diseases which results in various life-threatening cardiovascular diseases and the complications. In recent years, the treatment protocols for FH have diversified thanks to the deeper understanding of the disease in China and abroad and the development of new lipid-lowering drugs. However, the current awareness and diagnosis rate of FH are very low. The treatment of the disease is much inadequate. This paper summarizes the clinical characteristics, diagnosis, screening strategy, and treatment of FH hoping to enhance the understanding and awareness of the disease in the society.
Familial chylomicronemia syndrome: a novel mutation in the lipoprotein lipase gene
AbstractFamilial chylomicronemia syndrome (FCS) (OMIM: 238600) is a rare autosomal recessive disease caused by a biallelic loss-of-function mutation in the lipoprotein lipase (LPL) complex which includes LPL and its co-factors. Patients with FCS have severe hypertiglyceridemia (> 2000 mg/dL). We describe a 15-month-old boy with repeated pancreatitis episodes caused by severe hypertriglyceridemia. Genetic analysis revealed a novel homozygous mutation in the LPL gene, i.e. c.626T>G; p.(Leu209*). The mutation, carried by both parents, has been classified as a type 4 mutation which is likely pathogenic. Treatment aims at decreasing hypertriglyceridaemia by a low-fat diet (< 20g/day) eventually supplemented with medium chain triglyceride (MCT) fat to ensure caloric intake. In 2019, volanesorsen was approved by the European Medicines Agency (EMA) as adjunct treatment for adult patients with genetically proven FCS and persisting episodes of pancreatitis despite the diet.
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.
