DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Tangier disease — screening already-approved drugs against its 6-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleTangier disease maps to a 6-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 tangier 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
bestrophin 1 (BEST1) — BEST1 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 mc3drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8D1I · 1.82 Å · ligand 1,2-DIMYRISTOYL-RAC-GLYCERO-3-PHOSPHOCHOLINE (MC3). Experimental structure, not a prediction.
What the evidence adds up to
Tangier disease is an autosomal recessive disorder caused by mutations in the ABCA1 gene, which impairs cellular cholesterol export. Fewer than 100 cases have been described, though an estimated global prevalence of 1:640,000 suggests significant underdiagnosis. The disease results in very low levels of high-density lipoprotein (HDL) and apolipoprotein A-I, and cholesterol esters accumulate in peripheral tissues including the tonsils, spleen, lymph nodes, and nerves. Clinical hallmarks are orange-coloured enlarged tonsils, splenomegaly, peripheral neuropathy, and an increased risk of atherosclerotic cardiovascular disease. Diagnosis is confirmed by low HDL and apoA-I levels together with genetic testing for ABCA1 mutations.
A 2023 case report describes a 16-year-old girl with a novel phenotype involving predominant anterior horn cell damage. She had hip girdle weakness, waddling gait, progressive right leg atrophy, orange tonsils, soft skin, distal joint laxity, diffuse hypotonia, asymmetric leg wasting, moderate lower limb weakness, and hypoactive tendon reflexes. Creatine kinase was 70 U/L. Serum HDL and low-density lipoprotein were abnormally low. Whole-exome sequencing identified a novel homozygous splice site mutation c.2542+1G>A in ABCA1. The authors note that a high index of suspicion and search for peripheral markers is needed in patients with unusual anterior horn cell syndromes.
No cure exists. Management focuses on symptom control, cardiovascular risk reduction, and lifestyle and dietary changes intended to improve HDL function. A 2025 review states that ongoing research into gene therapies and new treatments offers hope for future breakthroughs, but no specific therapeutic agent is described as effective in any of the abstracts. What remains missing are well-designed clinical trials, patient stratification strategies, and dedicated funding to test any potential intervention in this ultra-rare population.
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 Indian Academy of Neurology · 2015 · 2 citations · open access
An uncommon cause of bifacial weakness and non-length-dependent demyelinating neuropathy
AbstractTangier disease is a rare metabolic disorder that causes neuropathy in half of the affected individuals. We present the clinical, electrophysiological, and histopathological findings in a middle-aged gentleman of Tangier disease who was initially diagnosed as leprosy and treated with antileprosy drugs. The presence of a demyelinating electrophysiology in a patient with predominant upper limb involvement and facial diplegia should raise the suspicion of Tangier disease. Estimation of serum lipids should form a part of routine evaluation in order to avoid misdiagnosis.
Zeitschrift für Gastroenterologie · 2022 · 0 citations
Unusual diagnosis of Tangier disease during screeningcolonoscopy
AbstractBackground Tangier disease is a rare, autosomal recessive genetic disorder associated with a deficiency in cellular cholesterol export leading to cholesterol accumulation in peripheral tissues (mainly in reticuloendothelial cells such as macrophages). While only ~100 cases have been described so far, the estimated global prevalence of 1:640.000 suggests significant underdiagnosis.
Journal of Education Health and Sport · 2025 · 0 citations · open access
From HDL Deficiency to Neuropathy: Insights into Tangier Disease
AbstractIntroduction: This review aims to provide a comprehensive examination of Tangier disease, focusing on its clinical manifestations, pathophysiology, and diagnostic methods. The article also delves into the available management strategies, the challenges in treating this rare condition, and the ongoing research into potential therapeutic interventions. Materials and Methods: A comprehensive review of the literature was conducted using the PubMed and Google Scholar databases with the following keywords: "Tangier disease", "HDL deficiency", "ABCA1", "neuropathy", "high-density lipoprotein ", "HDL", "apoA-I", "CETP", "atherosclerosis", "splenomegaly". Summary: Tangier disease is a rare autosomal recessive genetic disorder caused by mutations in the ABCA1 gene, which impairs cholesterol transport and results in low levels of HDL. This leads to the accumulation of cholesterol esters in various tissues, including the tonsils, spleen, lymph nodes, and nerves. The disease is characterized by orange-colored, enlarged tonsils, splenomegaly, peripheral neuropathy, and a heightened risk for atherosclerotic cardiovascular disease. Diagnosis is confirmed through low HDL and apoA-I levels, along with genetic testing for ABCA1 mutations. While no cure exists, treatment focuses on symptom management, controlling cardiovascular risks, and improving HDL function through lifestyle and dietary changes. Conclusions: Tangier disease, a rare genetic disorder caused by mutations in the ABCA1 gene, leads to severe lipid imbalances and various systemic complications. Although there is no cure, managing symptoms, controlling cardiovascular risks, and adopting lifestyle changes are essential for improving outcomes. Ongoing research into gene therapies and new treatments offers hope for future breakthroughs.
Journal of Clinical Neuromuscular Disease · 2023 · 0 citations
Atypical Presentation of Tangier Disease—Expanding the Clinical Spectrum
AbstractABSTRACT: Tangier disease is an autosomal recessive multisystem metabolic disorder with neuromuscular manifestations including peripheral neuropathy such as multifocal mononeuropathy or pseudosyringomyelia patterns. We report a novel phenotype of Tangier disease with predominant anterior horn cell involvement. A 16-year-old adolescent girl born to consanguineous parents had a 1-year history of hip girdle weakness with waddling gait and progressive atrophy of the right leg. She had orange tonsils, prominent lingual tonsils, soft skin, distal joint laxity, diffuse hypotonia with asymmetric wasting of legs, proximodistal moderate weakness in lower limbs, and tendon reflexes were hypoactive. The creatine kinase level was 70 U/L. Serum showed an abnormally low level of high- and low-density lipoprotein. Whole-exome sequencing showed a novel likely pathogenic splice site homozygous mutation c.2542+1G > A in the ABCA1 gene at intron 17. Hence, a high degree of suspicion and search for peripheral clinical markers is needed in patients with unusual anterior horn cell syndromes.
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.
