Nitisinone: A Promising Treatment for Black Bone Disease?

Author: AKU Society
Published: 14 Sep 2013 - Updated: 1 Dec 2025
Publication Type: Informative

Contents: Synopsis - Definition - Introduction - Main - Insights, Updates - Related Publications

Synopsis: This information provides a detailed overview of Alkaptonuria (AKU), commonly known as Black Bone Disease, a rare genetic disorder that causes the accumulation of homogentisic acid, leading to darkened, brittle bones, severe osteoarthritis, and other health complications. It highlights the promising potential of nitisinone as an effective treatment if administered early, emphasizing the urgent need for clinical trials to validate its efficacy. The article is authoritative as it is quality-reviewed and prepared by the AKU Society, offering practical insights for patients, caregivers, and medical professionals. It is particularly useful for those with disabilities or seniors managing degenerative conditions, as it explains symptoms, treatment challenges, and the importance of organized support for clinical participation.*

Topic Definition: Nitisinone

Nitisinone is a pharmaceutical compound originally developed to treat hereditary tyrosinemia type 1, a rare metabolic disorder, by inhibiting the enzyme 4-hydroxyphenylpyruvate dioxygenase. This inhibition prevents the accumulation of toxic metabolites that can damage the liver and kidneys. Beyond its initial use, nitisinone has shown potential in treating other metabolic conditions, most notably Alkaptonuria (Black Bone Disease), by reducing the buildup of homogentisic acid that leads to darkened connective tissues and progressive joint degeneration. Its precise mechanism and targeted action make it a significant advancement in managing rare metabolic disorders, offering patients an option to slow disease progression and improve quality of life.

Introduction

Alkaptonuria, or AKU for short, was the first genetic disease to be discovered more than 110 years ago. Despite this, it still has no cure, and the medical world remains largely unaware of its existence and impact on everyday life.

Main Content

Alkaptonuria (AKU) is a rare condition that may first be identified when a baby's urine turns dark brown or black when exposed to oxygen. The disease is also known as "AKU," "Alcaptonuria," "homogentisic acid oxidase deficiency," "Black Bone Disease", and "homogentisic acidura." It affects one out of 250,000 to 1 million people (especially in Slovakia and Dominican Republic) and can cause severe osteoarthritis in those affected. The buildup of acid in the body creates black pigment that attaches to cartilage surrounding the joints. This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Symptoms of Alkaptonuria

Alkaptonuria is often asymptomatic, but the sclera of the eyes may be pigmented (often only at a later age), and the skin may be darkened in sun-exposed areas and around sweat glands; sweat may be colored brown. Urine may turn brown or even inky black if collected and left exposed to open air, especially when left standing for a period of time. Kidney stones and stone formation in the prostate (in men) are common and may occur in more than a quarter of cases.

Three years ago, our CEO and Chairman, Nick Sireau, gave up his job in order to devote his time to finding a cure for AKU after his two kids were diagnosed. During these three years, he has worked tirelessly with teams in Liverpool, the United States and across Europe to plan a clinical trial. Now a very promising treatment called nitisinone has been found. When taken early enough in life, it's effectively a cure. The real challenge is proving that this drug works in a clinical trial, in order to license nitisinone for use in AKU. The cure will then become a reality.

AKU patients are scattered around the world, often faced with misdiagnosis, a lack of efficient care and a lack of awareness. This means patients from across Europe and beyond are needed to run a good clinical trial. They need assistance to:

• Support sister societies across the world.
• Help care for them properly while they are on the trial.
• Bring patients from across the world to their clinical trial centers.
• Support the work of the AKU Society, the patient group for people with Black Bone Disease.
• Organize events across Europe for patients with Black Bone Disease, in order to give patients everywhere access to information about the disease and the trials.
• Allow patients to bring carers with them when they attend the trial. As some of the patients are extremely disabled, traveling long distances by themselves can be extremely daunting.

Nick's vision is for children to never suffer the pain of Black Bone Disease.

Insights, Analysis, and Developments

Attribution/Source(s): This quality-reviewed publication was selected for publishing by the editors of Disabled World (DW) due to its relevance to the disability community. Originally authored by AKU Society and published on 14 Sep 2013, this content may have been edited for style, clarity, or brevity.

* Editorial additions by Ian C. Langtree.