RARE DISEASE
Tangier disease
Tangier disease
Tangier disease
Synonyms: ATP-binding cassette transporter A1 deficiency, Analphalipoproteinemia
Synonyms: ATP-binding cassette transporter A1 deficiency, Analphalipoproteinemia
Synonyms: ATP-binding cassette transporter A1 deficiency, Analphalipoproteinemia
Drug discovery
1
drug
With orphan designation
Overview
Tangier Disease Overview
Tangier disease is a rare autosomal recessive disorder caused by ABCA1 gene mutations, leading to near-absent HDL cholesterol (<5 mg/dL) and impaired cellular cholesterol efflux. Key clinical features include hepatosplenomegaly, orange-yellow tonsils, peripheral neuropathy (relapsing-remitting or syringomyelia-like), corneal opacities, and premature cardiovascular disease. Diagnosis involves lipid profiling (low HDL, apolipoprotein A-I) and genetic testing. Multisystem cholesterol deposition drives variable organ dysfunction, necessitating tailored monitoring [1][2][6][12].
Burden
Neuropathy: Present in >50% of cases, with progressive disability impacting quality of life [1][6][13].
Cardiovascular: Accelerated atherosclerosis despite low LDL-C; 30% develop coronary artery disease [3][7][10].
Systemic: Chronic organomegaly, thrombocytopenia, and diabetes risk due to pancreatic cholesterol deposition [6][12][18].
Therapies
Diet: Low-fat diet to reduce hepatic steatosis and atherosclerosis risk [1][14].
Symptomatic Management: Statins for elevated LDL-C; surgery (tonsillectomy) for obstructive symptoms [1][7].
Experimental: Gene therapy and HDL-enhancing agents under investigation; no curative therapies available [3][7][10].
Categories: rare endocrine diseases, rare genetic diseases, rare inborn errors of metabolism, rare neurological diseases
Research Papers
301 drug discovery papers about Tangier disease, with 3 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
301 drug discovery papers about Tangier disease, with 3 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-02-27 | ABCA1: A Therapeutic Target for Improving Cholesterol Homeostasis in Peripheral Neuropathies.
ATP-binding cassette A1 (ABCA1) is a critical molecule in facilitating cholesterol transport in a variety of organs. In the nervous system, cholesterol supply is essential and rate-limiting for myelin biogenesis, which underlies efficient conduction of nerve impulses. When myelin is damaged or improperly formed due to genetic defects, a host of neurological symptoms may arise. A rare form of peripheral neuropathy in Tangier disease (TD) patients is associated with autosomal recessive mutations in ABCA1. Accordingly, when ABCA1 loses its function due to misexpression, the neuropathic phenotype is over-represented. Independently, studies have revealed the altered expression of ABCA1 and dysregulation of cholesterol metabolism in a host of inherited peripheral neuropathies engaging the Peripheral Myelin Protein 22 (PMP22), suggesting shared pathophysiology. While the role of ABCA1 has not been investigated broadly in peripheral nerves, the transporter molecule is a therapeutic target for human disorders, including multiple sclerosis and Alzheimer's disease. Investigations in rodent models of type 1 Charcot-Marie-Tooth (CMT) neuropathies support the candidacy of this cholesterol transporter as a therapeutic target in efforts of peripheral myelin repair. Ongoing preclinical studies in central and peripheral nervous system disease models will provide critical information on the importance of ABCA1 as a target for disease modifying intervention.
2025-11-27 | From HDL Deficiency to Neuropathy: Insights into Tangier Disease
Introduction: 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.
2025-11-10 | Miglustat as a Treatment for Adults with Tangier Disease Neuropathy: The MUSTANG N-of-1 Trial with 21 months Clinical Observation.
Tangier disease (TD) is an ultra-rare disease, characterised by progressive peripheral neuropathy with no established treatment. To determine whether miglustat improved the clinical status of a single patient with TD, and to investigate the possible mechanisms of miglustat in this patient. An n-of-1 ABAB study, alternating on and off treatment for 6-month periods, total study duration of 2 years with an additional compassionate-access period of 21 months. Miglustat, an orphan drug licenced to treat Gaucher disease and Niemann-Pick disease, was repurposed. The study was designed with two co-primary endpoints: (a) time taken to complete the nine-hole peg test (fine motor control and finger dexterity), and (b) hand strength: grip and three-point pinch strength tests. Secondary endpoints were quality-of-life measures and biomarkers. A 21-year-old (at baseline) left-handed male patient with TD, diagnosed at the age of 6 months, and disabling neuropathy was included in the study. Over 2 years, there was a small signal in our clinical measures that the drug may be beneficial. Compared with the 2 years prior to treatment, the patient had no relapse of neuropathy during his study period and further extension. During the 21-month treatment extension, he showed considerable improvement on primary endpoints. Biomarkers changed as expected based on the mechanism of action of miglustat. Nerve conduction studies showed a mild benefit. Importantly, the patient's reported experience suggested a meaningful benefit from miglustat. Miglustat may be used to treat neurological complications of TD. This study showed that an n-of-1 study to inform a policy decision is practical and may offer hope to patients with rare diseases. ClinicalTrials.gov Identifier: ISRCTN17945917. Registration date: 07/06/2021; 'retrospectively registered'.
2026-02-27 | ABCA1: A Therapeutic Target for Improving Cholesterol Homeostasis in Peripheral Neuropathies.
ATP-binding cassette A1 (ABCA1) is a critical molecule in facilitating cholesterol transport in a variety of organs. In the nervous system, cholesterol supply is essential and rate-limiting for myelin biogenesis, which underlies efficient conduction of nerve impulses. When myelin is damaged or improperly formed due to genetic defects, a host of neurological symptoms may arise. A rare form of peripheral neuropathy in Tangier disease (TD) patients is associated with autosomal recessive mutations in ABCA1. Accordingly, when ABCA1 loses its function due to misexpression, the neuropathic phenotype is over-represented. Independently, studies have revealed the altered expression of ABCA1 and dysregulation of cholesterol metabolism in a host of inherited peripheral neuropathies engaging the Peripheral Myelin Protein 22 (PMP22), suggesting shared pathophysiology. While the role of ABCA1 has not been investigated broadly in peripheral nerves, the transporter molecule is a therapeutic target for human disorders, including multiple sclerosis and Alzheimer's disease. Investigations in rodent models of type 1 Charcot-Marie-Tooth (CMT) neuropathies support the candidacy of this cholesterol transporter as a therapeutic target in efforts of peripheral myelin repair. Ongoing preclinical studies in central and peripheral nervous system disease models will provide critical information on the importance of ABCA1 as a target for disease modifying intervention.
2025-11-27 | From HDL Deficiency to Neuropathy: Insights into Tangier Disease
Introduction: 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.
2025-11-10 | Miglustat as a Treatment for Adults with Tangier Disease Neuropathy: The MUSTANG N-of-1 Trial with 21 months Clinical Observation.
Tangier disease (TD) is an ultra-rare disease, characterised by progressive peripheral neuropathy with no established treatment. To determine whether miglustat improved the clinical status of a single patient with TD, and to investigate the possible mechanisms of miglustat in this patient. An n-of-1 ABAB study, alternating on and off treatment for 6-month periods, total study duration of 2 years with an additional compassionate-access period of 21 months. Miglustat, an orphan drug licenced to treat Gaucher disease and Niemann-Pick disease, was repurposed. The study was designed with two co-primary endpoints: (a) time taken to complete the nine-hole peg test (fine motor control and finger dexterity), and (b) hand strength: grip and three-point pinch strength tests. Secondary endpoints were quality-of-life measures and biomarkers. A 21-year-old (at baseline) left-handed male patient with TD, diagnosed at the age of 6 months, and disabling neuropathy was included in the study. Over 2 years, there was a small signal in our clinical measures that the drug may be beneficial. Compared with the 2 years prior to treatment, the patient had no relapse of neuropathy during his study period and further extension. During the 21-month treatment extension, he showed considerable improvement on primary endpoints. Biomarkers changed as expected based on the mechanism of action of miglustat. Nerve conduction studies showed a mild benefit. Importantly, the patient's reported experience suggested a meaningful benefit from miglustat. Miglustat may be used to treat neurological complications of TD. This study showed that an n-of-1 study to inform a policy decision is practical and may offer hope to patients with rare diseases. ClinicalTrials.gov Identifier: ISRCTN17945917. Registration date: 07/06/2021; 'retrospectively registered'.
Access all drug discovery articles and probability of success in trials forecasts:
Access all drug discovery articles and probability of success in trials forecasts:
Drug Discovery Landscape
1 orphan drug designation for Tangier disease.
1 orphan drug designation for Tangier disease.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Recombinant human apolipoprotein A-I in a complex with phospholipids | proteins | EMA | 2014-08-22 | — | Cerenis Therapeutics Holding SA |
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