Development of the first effective therapy for the rare disease Alkaptonuria

Alkaptonuria is a rare, hereditary metabolic disease, affecting 1 in every 250,000 – 1,000,000 people, that causes severe early-onset osteoarthritis. Starting from mid to late 20s, multiple joint replacements and medication for chronic pain are typical in patients. Researchers at the University of Liverpool developed the first effective pharmacological treatment option for the disease which transforms management and experience of the disease. Young people with alkaptonuria can now expect to live free of its debilitating symptoms whilst existing older patients are seeing symptoms arrested and some reversed.

The challenge

Alkaptonuria is a rare, hereditary metabolic disease that causes severe early-onset osteoarthritis, from bone and cartilage becoming black and brittle. Manifesting from mid to late 20s, multiple joint replacements and medication for chronic pain are typical in patients. Scope and quality of life are gradually reduced for patients e.g. mobility loss and dependence on carers, whilst high-risk surgeries are sometimes needed (heart valves). Alkaptonuria is the oldest known genetic disease; there has been no effective treatment until now. 

Our research

Professor Gallagher (expertise in bone and cartilage) was approached by the alkaptonuria patient group and a consultant at Royal Liverpool University Hospital, to explore how the bone and cartilage deterioration, characteristic of alkaptonuria, could be blocked.

During a ten-year period (2009-2019), the Liverpool team worked with nitisinone, eventually proving its efficacy as a therapy for alkaptonuria, through completing an observational study and clinical trials of the therapy. Findings included that at 12 months, homogentisic acid (HGA), the cause of alkaptonuria, was decreased by 99.7%.

Disease prevention

Based on Liverpool’s trial results, pharmaceutical company Swedish Orphan Biovitrum applied to the European Medicine Agency (EMA) to license the treatment, as Orfadin. EMA granted the license with the EU market size estimated as 2,275 patients, with 30-50 new patients identified each year.

In the UK uptake has been close to 100 per cent of known England and Scotland cases. Several patients from Wales, Northern Ireland, and internationally self-fund for the treatment.

The NHS England Highly Specialised Service for alkaptonuria patients, the National Alkaptonuria Service (where all UK patients are referred) found that of all patients who had been seen for over a year, improvements were present in all domains of the SF36 quality of life scale except energy/fatigue.

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