Tuesday, August 12, 2014

CAMBRIDGE, UK – 12/08/14: A new mechanism of joint destruction has been discovered for the first time during research in to the rare disease, alkaptonuria. The research was conducted by University of Liverpool scientists, supported by the AKU Society. A natural material that grinds away healthy cartilage and worsens osteoarthritis has been identified in human hip joints.

The scientists, alongside Prof Alan Boyde and colleagues from Queen Mary University of London, were studying the hip of a man with alkaptonuria (AKU). Alkaptonuria patients produce excess homogentisic acid (HGA) because the enzyme which usually breaks down HGA is faulty. In adult patients the build-up of HGA causes cartilage to breakdown and become black and brittle.

The study revealed the presence of high density mineralised protrusions (HDMP), which have only been seen before in horses. These protrusions are caused as the body acts to fill in cracks in joint cartilage and can snap off, leading to sharp, dense particles in the joint which grind against healthy tissue.

Professor Jim Gallagher led the study in Liverpool. He said: “There is no cure for osteoarthritis, but it is one of the leading causes of disability, causing immense pain and difficulty of movement to sufferers.

“The discovery of HDMP in humans means that for the first time we are seeing an important mechanism in the process which causes the disease. In effect these small, sharp particles could act like an abrasive powder scouring the surfaces of the joint.”

To confirm the findings, the team studied eight hips donated for research by people with osteoarthritis and found the same results as in the alkaptonuria patient.

The team studied the joint without using the decalcification method, which is typically used to make bones softer and easier to study. This process, which involves using acid, would normally destroy the HDMPs.

Professor Gallagher, from the University’s Institute of Ageing and Chronic Disease concluded: “Studying a rare illness like alkaptonuria is a worthwhile project in itself, but it can also help with new insights into much more common diseases.

“This is a case in point, and because of our work on alkaptonuria, we are now able to add a new piece to the puzzle of an illness that affects millions.”

The study, published in the Journal of Anatomy, recommends that searching for these HDMPs should now be included in the study of patients with osteoarthritis.

The study was supported by the AKU Society and the Rosetrees Trust. The AKU Society helped fund initial research and has continued to support funding applications made by the University of Liverpool.

Read the full paperhere


Notes to editors: A copy of the paper is available on request to the University of Liverpool Press Office.

1. Photographs and the full paper are available on request.

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About alkaptonuria Alkaptonuria or AKU was the first genetic disease to be identified 110 years ago[i]. It is caused by a recessive gene on chromosome three leading to a deficiency of a key enzyme (HGD) that activates one of the steps in the breakdown of the amino acid tyrosine[ii]. The deficiency means that patients are unable to break down protein correctly. Homogentisic acid accumulates in body tissue, leading to the breakdown of cartilage, which becomes black and brittle[iii]. It affects one in every 250,000 people.

Damaged cartilage breaks away; causing early-onset osteoarthritis and joint destruction, which often leads to joint replacement surgery in middle age[iv].

The debilitating nature of the disease means that many patients are unable to work. Currently, there is no approved treatment for AKU, apart from painkillers and physiotherapy offered to combat pain. Many patients go on to need joint replacements for their damaged knees, hips and shoulders[v].

About the AKU Society The AKU Society was founded in 2003 in Liverpool by AKU sufferer Bob Gregory and his doctor, Dr Lakshminarayan Ranganath of the Royal Liverpool and Broadgreen University Hospitals. It was the first AKU charity in the world. It is patient-led and includes patients, relatives, medical experts and friends and carers among its supporters. The society offers people with AKU help and support, raises awareness of AKU and supports research into its treatment. Its vision is to find a cure for AKU within the next decade.

The AKU Society has established an influential multidisciplinary network, including representatives from numerous universities and hospitals, pharmaceutical companies and national AKU patient groups in Europe, the Middle East, Asia and North America. The society has also funded two research programmes into AKU and the first AKU information centre.

[i] Introne, W, L. et al. 2011. A 3-year randomised therapeutic trial of nitisinone in alkaptonuria. Molecular Genetics and Metabolism, 103, 207-314.[ii] Zatkova, A. 2011. An update on molecular genetics of alkaptonuria AKU. Journal of Inherited Metabolic Disorders, published online.[iii] Phornphutkul, C. et al. 2002. Natural history of alkaptonuria. The New England Journal of Medicine, 347(26), 2111- 2121.[iv] Ranganath, L., & Cox, T. 2011. Natural history of AKU revisited: analyses based on scoring systems. Journal of Inherited Metabolic Disorders, published online.[v] Suwannarat, P. 2005. Use of nitisinone in patients with alkaptonuria. Metabolism: Clinical and Experimental, 54, 719-728.