AKU Society

Liverpool, UK, 18 November 2011 - A campaigning patient group has today launched a five million-pound appeal to fund a ground-breaking clinical trial to test the drug nitisinone as a potential treatment for alkaptonuria (AKU), commonly known as black bone disease.

Although a rare disease, medical researchers at the AKU Society believe an effective treatment for the condition could also open new lines of inquiry into treating the millions of patients in the UK who suffer from osteoarthritis.

“Anything we can do to understand AKU, which is a severe form of arthritis, will undoubtedly help us to understand other forms of arthritis such as osteoarthritis” said Dr Lakshminarayan Ranganath, Medical Director for the AKU Society. “Osteoarthritis is a highly prevalent disease affecting at least eight million people in the UK."(i)

“Normally, clinical trials are designed and developed by pharmaceutical companies as it’s a complicated and expensive business,” said Nick Sireau, AKU Society Chairman, whose two young sons suffer from the rare genetic condition. “No pharmaceutical company as yet has committed to take on the Phase III trial. We hope they will, but if necessary we will take on both the development and the fundraising - and pay for it ourselves.”

The AKU Society will launch the campaign at the opening of its annual conference in Liverpool today, attended by more than 80 medical researchers from around the world. The society believes it could soon lead to the first treatment for AKU, with the potential to improve patients’ quality of life dramatically.

Nick’s hard work could mean his two young sons, diagnosed as babies with AKU, will not have to suffer the debilitating consequences of the disease, which typically leads to severe joint pain, early-onset osteoarthritis, an inability to work and the need for joint replacement surgery in middle age.

AKU sufferer, Simon Laxon from Coventry, aged 45, was a keen sportsman and black belt in Kung Fu before his AKU condition led to severe joint and back pain, putting a stop to his active lifestyle.

“I feel like a 45-year-old in a 90-year-old’s body,’’ he said. “As the condition has progressed, my mobility is so restricted that I’ve also lost my job as a result. It’s encouraging but also frustrating to know that a potential treatment exists that could help as we need more clinical evidence before doctors can prescribe it for AKU.”

Simon was offered the chance to take part in an earlier US study using the drug nitisinone. Simon recalls that while on nitisinone the pain seemed to completely disappear. “I was able to play with my children again – something I haven’t been able to do in years.” Simon describes this potential treatment as a glimmer of

hope. ‘’I tasted it and now it’s been taken away,’’ he added. He urges that the new trial should go forward so that future generations will not have to suffer the same ordeal as he has undergone.

Alkaptonuria or AKU was the first genetic disease ever discovered (ii). It is caused by a recessive gene on chromosome three leading to a deficiency of a key enzyme (HGD) which activates one of the steps in the breakdown of the amino acid tyrosine (iii). The deficiency means that patients are unable to break down protein correctly and homogentisic acid accumulates in body tissue, leading to the breakdown of cartilage, which becomes black and brittle. (iv)

Damaged cartilage breaks away, causing early-onset osteoarthritis and joint destruction which often leads to joint replacement surgery in middle age. (v) Also noticeable are black spots in the ears and eyes; kidney and prostate stones; tendon, ligament and muscle ruptures; and black urine. Calcification of blood vessels and heart valves also means that there is an increased likelihood of developing heart disease. (iv)

The debilitating nature of the disease means that many AKU patients are unable to work. Currently, there is no approved treatment for AKU, apart from painkillers and physiotherapy offered to combat the intense pain felt by patients. Despite such therapy, many go on to need joint replacement surgery to replace the function of their damaged knees, hips and shoulders. (vi)

Nitisinone has been found in early clinical trials to reduce homogentisic acid levels by 95%, resulting in patients reporting significantly reduced joint and back pain. (vii)

Researchers believe that if nitisinone is administered early enough it could prevent the toxic acid from building up (iv), allowing sufferers to lead a normal, pain-free life.

Nitisinone is licensed for the treatment of another metabolic disorder, tyrosinaemia type 1, and marketed as Ordafin® for tyrosinaemia type 1 by Swedish Orphan Biovitrum (www.sobi.com).

The AKU Society (www.alkaptonuria.info) 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 aims to locate AKU sufferers to offer them help and support, to raise awareness of AKU and to support 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 12 universities and hospitals, seven pharmaceutical companies and four national AKU patient groups in Europe and North America. The society has also funded two research programmes into AKU and the first AKU information centre

Lisa Stevens 

Tudor Reilly 

Phone: 020 7034 3210 

e-mail: lisa.stevens@tudor-reilly.com 

Nick Sireau

AKU Society Chairman

Phone: 0788 670 9633

e-mail: nick@akusociety.org

(i) http://www.arthritisresearchuk.org/arthritis_information/arthritis_types__symptoms/osteoarthritis.aspx

(ii) Introne, W, L. et al. 2011. A 3-year randomised therapeutic trial of nitisinone in alkaptonuria. Molecular Genetics and Metabolism, 103, 207-314.

(iii) Zatkova, A. 2011. An update on molecular genetics of alkaptonuria AKU. Journal of Inherited Metabolic Disorders, published online.

(iv) Phornphutkul, C. et al. 2002. Natural history of alkaptonuria. The New England Journal of Medicine, 347(26), 2111-2121.

(v) Ranganath, L., & Cox, T. 2011. Natural history of AKU revisited: analyses based on scoring systems. Journal of Inherited Metabolic Disorders, published online.

(vi) Suwannarat, P. 2005. Use of nitisinone in patients with alkaptonuria. Metabolism: Clinical and Experimental, 54, 719-728.

(vii) Laxon, S., Ranganath, L., & Timmis O. 2011. A patients journey: Living with alkaptonuria. British Medical Journey, 343.