ArticleJIMD reports2015
Nitisinone Arrests but Does Not Reverse Ochronosis in Alkaptonuric Mice.
Article in JIMD reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 50 citations in OpenAlex.
- Nitisinone Treatment Affects Biomarkers of Bone and Cartilage Remodelling in Alkaptonuria Patients.International journal of molecular sciences · 2023Trial
- Quantification of the flux of tyrosine pathway metabolites during nitisinone treatment of Alkaptonuria.Scientific reports · 2019Trial
- Article
- An anatomical investigation of alkaptonuria: Novel insights into ochronosis of cartilage and bone.Journal of anatomy · 2025Article
- Article
- Revisiting Quantification of Phenylalanine/Tyrosine Flux in the Ochronotic Pathway during Long-Term Nitisinone Treatment of Alkaptonuria.Metabolites · 2022Article
- Metabolomic studies in the inborn error of metabolism alkaptonuria reveal new biotransformations in tyrosine metabolism.Genes & diseases · 2022Article
- "Lessons from Rare Forms of Osteoarthritis".Calcified tissue international · 2021Review
- Development of an Effective Therapy for Alkaptonuria - Lessons for Osteoarthritis.Rheumatology and immunology research · 2021Review
- Alkaptonuria with extensive ochronotic degeneration of the Achilles tendon and its surgical treatment: a case report and literature review.Asian biomedicine : research, reviews and news · 2021Article
- A Mimic of Ankylosing Spondylitis, Ochronosis: Case Report and Review of the Literature.Current allergy and asthma reports · 2021Review
- Article
- Reversal of ochronotic pigmentation in alkaptonuria following nitisinone therapy: Analysis of data from the United Kingdom National Alkaptonuria Centre.JIMD reports · 2020Article
- Pigmentation Chemistry and Radical-Based Collagen Degradation in Alkaptonuria and Osteoarthritic Cartilage.Angewandte Chemie (International ed. in English) · 2020Article
- Dietary restriction of tyrosine and phenylalanine lowers tyrosinemia associated with nitisinone therapy of alkaptonuria.Journal of inherited metabolic disease · 2020Observational
- Alkaptonuria: Current Perspectives.The application of clinical genetics · 2020Review
- A robust bacterial assay for high-throughput screening of human 4-hydroxyphenylpyruvate dioxygenase inhibitors.Scientific reports · 2019Article
- Concentric lamellae - novel microanatomical structures in the articular calcified cartilage of mice.Scientific reports · 2019Article
- Musculoskeletal manifestations of alkaptonuria: A case report and literature review.European journal of rheumatology · 2019Review
- Asymptomatic Corneal Keratopathy Secondary to Hypertyrosinaemia Following Low Dose Nitisinone and a Literature Review of Tyrosine Keratopathy in Alkaptonuria.JIMD reports · 2018Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alkaptonuria (AKU) is an ultrarare autosomal recessive disorder resulting from a deficiency of homogentisate 1,2 dioxygenase (HGD), an enzyme involved in the catabolism of phenylalanine and tyrosine. Loss of HGD function prevents metabolism of homogentisic acid (HGA), leading to increased levels of plasma HGA and urinary excretion. Excess HGA becomes deposited in collagenous tissues and subsequently undergoes polymerisation, principally in the cartilages of loaded joints, in a process known as ochronosis. This results in an early-onset, devastating osteoarthropathy for which there is currently no effective treatment. We recently described the natural history of ochronosis in a murine model of AKU, demonstrating that deposition of ochronotic pigment begins very early in life and accumulates with age. Using this model, we were able to show that lifetime treatment with nitisinone, a potential therapy for AKU, was able to completely prevent deposition of ochronotic pigment. However, although nitisinone has been shown to inhibit ochronotic deposition, whether it can also facilitate removal of existing pigment has not yet been examined. We describe here that midlife administration of nitisinone to AKU mice arrests further deposition of ochronotic pigment in the tibiofemoral joint, but does not result in the clearance of existing pigment. We also demonstrate the dose-dependent response of plasma HGA to nitisinone, highlighting its efficacy for personalised medicine, where dosage can be tailored to the individual AKU patient.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.