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DeCure for Familial hypobetalipoproteinemia 1

DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for familial hypobetalipoproteinemia 1 — 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 module1 genesLead labRare & Orphan
All cures
Rare & OrphanDOID:0111062$DeCureRare

The disease map

Disease moduleFamilial hypobetalipoproteinemia 1 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 familial hypobetalipoproteinemia 1 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.

What the evidence adds up to

A 2008 report described a family in which two counteracting mutations in the APOB gene were transmitted. A 38-year-old man and two of his children had elevated LDL cholesterol and apolipoprotein B100 caused by the R3500Q mutation underlying familial defective apolipoprotein B. His spouse and a third child had substantially reduced levels. The two mutations neutralised each other, producing a clinically normolipidemic phenotype. No treatment was administered or tested in this family study.

A 1976 report described a family with hypobetalipoproteinaemia containing 10 affected members. In six patients, LDL cholesterol concentrations were about 10% of normal. In four patients, LDL cholesterol was reduced to about 50% of normal; these four were thought to represent an intermediate form. The variation in total cholesterol and LDL cholesterol among affected individuals in the same family could reflect differences in expression of a single gene or additive expression of a gene at a second locus.

A 1993 case report described a 37-year-old asymptomatic Lebanese woman with a serum total cholesterol of 1.1 mmol/L, HDL cholesterol of 1.0 mmol/L, and triglycerides of 0.28 mmol/L. Her apolipoprotein B level was markedly reduced at 0.07 g/L. All family members except one daughter had apo B levels about 25% of normal; that daughter had undetectable apo B levels. The pattern of inheritance was autosomal dominant. No treatment was given.

No drug has been tested in any of these reports. What is missing is any clinical trial of a drug intended to raise LDL or apo B in these patients, any systematic natural history study with hard endpoints such as hepatic steatosis progression or cardiovascular events, and any stratification by the specific APOB mutation or by the degree of LDL reduction.

Evidence

Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.

Annals of Internal Medicine · 2008 · 15 citations

Familial Defective Apolipoprotein B and Familial Hypobetalipoproteinemia in One Family: Two Neutralizing Mutations

AbstractLetters6 May 2008Familial Defective Apolipoprotein B and Familial Hypobetalipoproteinemia in One Family: Two Neutralizing MutationsAnouk van der Graaf, MD, Sigrid W. Fouchier, PhD, Maud N. Vissers, PhD, Joep C. Defesche, PhD, Albert Wiegman, MD, PhD, Raaj R. Sankatsing, MD, Barbara A. Hutten, PhD, Mieke D. Trip, MD, PhD, and John J.P. Kastelein, MD, PhDAnouk van der Graaf, MDFrom Academic Medical Centre, University of Amsterdam, Amsterdam 1105 AZ, Netherlands., Sigrid W. Fouchier, PhDFrom Academic Medical Centre, University of Amsterdam, Amsterdam 1105 AZ, Netherlands., Maud N. Vissers, PhDFrom Academic Medical Centre, University of Amsterdam, Amsterdam 1105 AZ, Netherlands., Joep C. Defesche, PhDFrom Academic Medical Centre, University of Amsterdam, Amsterdam 1105 AZ, Netherlands., Albert Wiegman, MD, PhDFrom Academic Medical Centre, University of Amsterdam, Amsterdam 1105 AZ, Netherlands., Raaj R. Sankatsing, MDFrom Academic Medical Centre, University of Amsterdam, Amsterdam 1105 AZ, Netherlands., Barbara A. Hutten, PhDFrom Academic Medical Centre, University of Amsterdam, Amsterdam 1105 AZ, Netherlands., Mieke D. Trip, MD, PhDFrom Academic Medical Centre, University of Amsterdam, Amsterdam 1105 AZ, Netherlands., and John J.P. Kastelein, MD, PhDFrom Academic Medical Centre, University of Amsterdam, Amsterdam 1105 AZ, Netherlands.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-148-9-200805060-00022 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Background: Some hereditary disorders of lipoprotein metabolism can be characterized by hyper- as well as hypocholesterolemia. We describe a family in which 2 counteracting mutations in the apolipoprotein B gene (APOB) were transmitted and resulted in a clinically normolipidemic phenotype.Case Report: A 38-year-old man (index patient [patient II-4 in Figure]) and 2 of his children (patients III-1 and III-3) had elevated levels of low-density lipoprotein (LDL) cholesterol and apolipoprotein B100 (apoB) caused by a point mutation (R3500Q) in APOB, underlying familial defective apolipoprotein B (FDB). In contrast, his spouse (patient II-3) and a third child (patient III-4) had substantially ...References1. Fouchier SW, Sankatsing RR, Peter J, Castillo S, Pocovi M, Alonso R, et al. High frequency of APOB gene mutations causing familial hypobetalipoproteinaemia in patients of Dutch and Spanish descent. J Med Genet. 2005;42:23. [PMID: 15805152] CrossrefMedlineGoogle Scholar2. Schonfeld G, Patterson BW, Yablonskiy DA, Tanoli TS, Averna M, Elias N, et al. Fatty liver in familial hypobetalipoproteinemia: triglyceride assembly into VLDL particles is affected by the extent of hepatic steatosis. J Lipid Res. 2003;44:470-8. [PMID: 12562873] CrossrefMedlineGoogle Scholar3. Tanoli T, Yue P, Yablonskiy D, Schonfeld G. Fatty liver in familial hypobetalipoproteinemia: roles of the APOB defects, intra-abdominal adipose tissue, and insulin sensitivity. J Lipid Res. 2004;45:941-7. [PMID: 14967820] CrossrefMedlineGoogle Scholar4. Sankatsing RR, Fouchier SW, de Haan S, Hutten BA, de Groot E, Kastelein JJ, et al. Hepatic and cardiovascular consequences of familial hypobetalipoproteinemia. Arterioscler Thromb Vasc Biol. 2005;25:1979-84. [PMID: 16002743] CrossrefMedlineGoogle Scholar5. Kastelein JJ, Wedel MK, Baker BF, Su J, Bradley JD, Yu RZ, et al. Potent reduction of apolipoprotein B and low-density lipoprotein cholesterol by short-term administration of an antisense inhibitor of apolipoprotein B. Circulation. 2006;114:1729-35. [PMID: 17030687] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Academic Medical Centre, University of Amsterdam, Amsterdam 1105 AZ, Netherlands.Disclosures: None disclosed. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited BySuccessful Genetic Screening and Creating Awareness of Familial Hypercholesterolemia and Other Heritable Dyslipidemias in the NetherlandsCan one overcome "unhealthy genes"?The complex molecular genetics of familial hypercholesterolaemiaFamilial hypercholesterolaemiaGenotype-guided diagnosis in familial hypercholesterolemiaCardiovascular risk in relation to functionality of sequence variants in the gene coding for the low-density lipoprotein receptor: a study among 29 365 individuals tested for 64 specific low-density lipoprotein-receptor sequence variantsGenetic variation in APOB , PCSK9 , and ANGPTL3 in carriers of pathogenic autosomal dominant hypercholesterolemic mutations with unexpected low LDL-Cl LevelsLiteraturAssessment of Carotid Atherosclerosis in Normocholesterolemic Individuals With Proven Mutations in the Low-Density Lipoprotein Receptor or Apolipoprotein B GenesFunctionality of sequence variants in the genes coding for the low-density lipoprotein receptor and apolipoprotein B in individuals with inherited hypercholesterolemiaTwo Years after Molecular Diagnosis of Familial Hypercholesterolemia: Majority on Cholesterol-Lowering Treatment but a Minority Reaches Treatment GoalHipobetalipoproteinemia familiar: caracterización clínica de una nueva mutación en el gen de la apolipoproteína B 6 May 2008Volume 148, Issue 9Page: 712-714KeywordsApolipoproteinsCholesterolHypercholesterolemiaLipoprotein metabolismLipoproteinsLiverMutationStable coronary artery diseaseVitamins ePublished: 6 May 2008 Issue Published: 6 May 2008 CopyrightCopyright © 2008 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...

https://doi.org/10.7326/0003-4819-148-9-200805060-00022
Clinical Genetics · 1976 · 12 citations

Further observations on familial hypobetaliproteinaemia

AbstractA family with hypobetalipoproteinaemia with 10 affected members is described. In six patients low density lipoprotein cholesterol (LDL-c) concentrations were about 10 % of normal. In four LDL-c was reduced to about 50 % of normal; these four patients probably represent the "intermediate" form of hypobetalipoproteinaemia. This variation in total cholesterol concentration and LDL-c among the affected individuals of the same family could reflect differences of expression in a single aberrant gene or additive expression of a gene at a second locus.

https://doi.org/10.1111/j.1399-0004.1976.tb01561.x
The Medical Journal of Australia · 1993 · 7 citations

Familial hypobetalipoproteinaemia: a rare presentation to the lipid clinic

AbstractOBJECTIVE: To report a case of familial hypobetalipoproteinaemia in a woman who presented after the incidental finding of marked hypocholesterolaemia during laboratory tests. CLINICAL FEATURES: An asymptomatic 37-year-old Lebanese woman presented to the lipid clinic with a serum total cholesterol concentration of 1.1 mmol/L, high density lipoprotein (HDL) cholesterol of 1.0 mmol/L, and triglycerides of 0.28 mmol/L. No secondary cause for the hypocholesterolaemia was established. INVESTIGATION AND OUTCOME: Her serum apolipoprotein B (apo B) levels were markedly reduced at 0.07 g/L. Except for one daughter (IV-4), all other family members including her husband (her first cousin) had apo B levels about 25% of normal. Daughter IV-4 had undetectable apo B levels. Family studies confirmed an autosomal dominant pattern of inheritance consistent with familial hypobetalipoproteinaemia. CONCLUSION: Familial hypobetalipoproteinaemia is a rare condition that should be considered in the differential diagnosis of hypocholesterolaemia. Absence of clinical features, autosomal dominant pattern of inheritance, and reduced apo B levels suggest the diagnosis.

https://doi.org/10.5694/j.1326-5377.1993.tb137834.x

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.