Managing Alkaptonuria: 2 mg Nitisinone can restrict ochronosis
M3 India Newsdesk Sep 22, 2018
A first of its kind observational study conducted by a Liverpool based research collaboration has reported that nitisinone can treat the extremely rare genetic disease alkaptonuria (AKU) by restricting disease progression.
Recently results of a prospective observational study were published which had sought to find out if Nitisinone prevents the clinical progression of the Alkaptonuria.
A quick look at Alkaptonuria (AKU)
AKU is also called a black bone disease, which is a genetic condition, in which the enzyme called homogentisate dioxygenase is deficient. Deficiency of this enzyme causes accretion of homogentisic acid (HGA), which is deposited as a black pigment in tissues, as part of a process known, as ochronosis. Over a period of time, this results in progressive damage if no treatment is offered. The progressive damage can involve joints and spine, which may necessitate repeat joint surgeries. Patients can also develop stones involving kidney, prostate, gallbladder, salivary, osteoporosis, and rupture of tendons, ligament, and muscle. It can also affect the heart valves.
This particular observational study concluded that 2 mg of daily nitisinone inhibited ochronosis and significantly slowed the progression of AKU over a three-year period.
It is known that nitisinone reduces homogentisic acid (HGA), but there is a lack of data on whether nitisinone can amend the progression of Alkaptonuria (AKU).
Hence, this study was sought and it evaluated 39 AKU patients, who received 2 mg of nitisinone every day for a period of 3 years. The severity was assessed by calculating the AKU Severity Score Index (AKUSSI) so as to enable comparison between nitisinone and pre-nitisinone phases.
Key findings
- During the study period the ALL (sum of clinical, joint and spine AKUSSI features) AKUSSI rate of change of scores/patient/month, was significantly lesser at two and three years post-nitisinone compared to pre-nitisinone (p <.01).
- Ear and ocular ochronosis rate of change of scores/patient/month were also significantly lesser at all three years.
The result of the study implied that nitisinone prevents the progression of the disease, by reducing HGA (homogentisic acid). Moreover, nitisinone therapy also to some extent reversed ochronosis.
This study is the first of its kind suggesting that a 2 mg dose of nitisinone prevents clinical progression of AKU. Results also showed that the drug can decrease the impact of ochronosis, particularly in joints and the intensity of osteoarthritis was much lesser and risk of heart disease was lesser during the study.
Source: Ranganath LR, et al. Nitisinone arrests ochronosis and decreases rate of progression of Alkaptonuria: Evaluation of the effect of nitisinone in the United Kingdom National Alkaptonuria Centre. Mol Genet Metab. 2018 Jul 24. pii: S1096-7192(18)30177-X.
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