DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for abetalipoproteinemia — 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 moduleAbetalipoproteinemia 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 abetalipoproteinemia 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
microsomal triglyceride transfer protein (MTTP) — MTTP 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 pgedrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6I7S · 2.5 Å · ligand TRIETHYLENE GLYCOL (PGE). Experimental structure, not a prediction.
What the evidence adds up to
Abetalipoproteinemia is caused by biallelic pathogenic mutations in the MTTP gene, which stops the assembly of apolipoprotein B-containing lipoproteins in the intestine and liver. This leads to fat and fat-soluble vitamin malabsorption and severe hypolipidemia. Infants typically present with steatorrhea, vomiting, and failure to thrive. Later, deficiency of fat-soluble vitamins produces haematological problems (acanthocytosis, anaemia, bleeding tendency), neuromuscular disease (spinocerebellar ataxia, peripheral neuropathy, myopathy), and ophthalmological symptoms such as retinitis pigmentosa. Untreated, the disease can be debilitating and lethal by the third decade from blindness, neuromyopathy, or respiratory failure.
High-dose vitamin supplementation is the mainstay of treatment and may prevent, delay, or alleviate complications, allowing some patients to live into the eighth decade. However, it cannot fully prevent or restore impaired function. A 1967 study found that a lipid-free protein immunologically identical to the apoprotein of beta-lipoprotein (B protein) is present in plasma from patients with abetalipoproteinemia, suggesting the disease is not caused by an inability to synthesise B protein but possibly by a defect in assembling the complete beta-lipoprotein macromolecule.
A 2021 review proposes diagnostic criteria for Japanese government financial support, using low-density lipoprotein cholesterol below 15 mg/dL and apolipoprotein B below 15 mg/dL as entry criteria for screening. Registry research is ongoing to understand the disease burden and unmet needs of this life-threatening condition with few therapeutic options. What remains missing is a therapy that addresses the underlying MTTP defect rather than only supplementing vitamins, along with the funding and trial design needed to test such an approach in a very small patient population that would require careful stratification by age and existing complications.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Atherosclerosis and Thrombosis · 2021 · 52 citations · open access
Current Diagnosis and Management of Abetalipoproteinemia
AbstractAbetalipoproteinemia (ABL) is a rare autosomal recessive disorder caused by biallelic pathogenic mutations in the MTTP gene. Deficiency of microsomal triglyceride transfer protein (MTTP) abrogates the assembly of apolipoprotein (apo) B-containing lipoprotein in the intestine and liver, resulting in malabsorption of fat and fat-soluble vitamins and severe hypolipidemia. Patients with ABL typically manifest steatorrhea, vomiting, and failure to thrive in infancy. The deficiency of fat-soluble vitamins progressively develops into a variety of symptoms later in life, including hematological (acanthocytosis, anemia, bleeding tendency, etc.), neuromuscular (spinocerebellar ataxia, peripheral neuropathy, myopathy, etc.), and ophthalmological symptoms (e.g., retinitis pigmentosa). If left untreated, the disease can be debilitating and even lethal by the third decade of life due to the development of severe complications, such as blindness, neuromyopathy, and respiratory failure. High dose vitamin supplementation is the mainstay for treatment and may prevent, delay, or alleviate the complications and improve the prognosis, enabling some patients to live to the eighth decade of life. However, it cannot fully prevent or restore impaired function. Novel therapeutic modalities that improve quality of life and prognosis are awaited. The aim of this review is to 1) summarize the pathogenesis, clinical signs and symptoms, diagnosis, and management of ABL, and 2) propose diagnostic criteria that define eligibility to receive financial support from the Japanese government for patients with ABL as a rare and intractable disease. In addition, our diagnostic criteria and the entry criterion of low-density lipoprotein cholesterol (LDL-C) ＜15 mg/dL and apoB ＜15 mg/dL can be useful in universal or opportunistic screening for the disease. Registry research on ABL is currently ongoing to better understand the disease burden and unmet needs of this life-threatening disease with few therapeutic options.
Journal of Lipid Research · 1967 · 45 citations · open access
Immunological evidence for the presence of B protein (apoprotein of Β-lipoprotein) in normal and abetalipoproteinemic plasma
AbstractThe antigenicity of -lipoprotein that had been chemically altered by acetylation or arsanilation was compared with that of native beta-lipoprotein, of lymph chylomicrons, of plasma proteins with d > 1.21, and of plasma from patients with abetalipoproteinemia. Chemical alteration causes structural changes in beta-lipoprotein which render it immunologically identical with a protein that is present both in normal plasma and in plasma from patients with abetalipoproteinemia. This protein has been identified by immunoelectrophoresis as abeta -globulin which does not stain for lipid. It is presumed to be the lipid-free apoprotein of beta-lipoprotein (B protein). The findings suggest that abetalipoproteinemia is not due to inability to synthesize B protein, but might instead be due to a defect in the formation of the complete beta-lipoprotein macro-molecule.
Oxford University Press eBooks · 2016 · 0 citations
Abetalipoproteinemia and Hypobetalipoproteinemia
AbstractAbetalipoproteinemia and hypobetalipoproteinemia are characterized by marked hypocholesterolemia and are classified depending on the lipid biochemical phenotype, gene involved, and mode of inheritance of the condition together with the severity of the mutation or mutations present. These disorders may or may not be associated with clinical manifestations such as fat malabsorption, growth failure, fat-soluble vitamin deficiency, fatty liver disease, and neuro-ophthalmological dysfunction. Early diagnosis and treatment with dietary modification and replacement of fat-soluble vitamins can prevent the clinical complications.
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.
