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‘Magic bullet’ offers hope to patients with rare genetic disease

10 November 2010 Sunderland, University of

A ‘magic bullet’ designed by pharmaceutical scientists at an English university could eradicate the side effects of a drug used to treat a rare genetic disease. Researchers at the University of Sunderland have chemically modified a drug used to treat cystinosis - a disease which occurs when the body’s mechanism to remove excess cystine (an amino acid) breaks down, leading to kidney problems and eventually affecting other organs - to remove unpleasant side effects such as nausea, vomiting, severe halitosis, body odour and a noxious taste.

The unpleasant side effects of a life-saving drug used to treat patients with a rare genetic disease could be eradicated thanks to a ‘magic bullet’ designed by pharmaceutical scientists at a North East university.

Professor Roz Anderson and PhD student Lisa Frost, at the University of Sunderland, have chemically modified a drug used to treat cystinosis - a disease which occurs when the body’s mechanism to remove excess cystine (an amino acid) breaks down, leading to kidney problems and eventually affecting other organs.
There is still no cure, and if left untreated cystinosis can result in kidney failure before a child reaches the age of 10; it’s rare for patients to live beyond the age of 40.
Drugs used successfully to treat patients with the disease contain the active ingredient cysteamine; however, this produces side effects such as nausea, vomiting, severe halitosis, body odour and a noxious taste. A large dose of the drug four times a day is also required to treat the disease, as 70 per cent is wasted through the body’s metabolism during digestion, with no therapeutic benefit.
However, Prof Anderson and Lisa have modified the drug which targets cysteamine directly into the cells, aiming to improve its absorption into the body, reduce the amount needed to be taken and lower the adverse side effects.
Prof Anderson said: “You can imagine how difficult it is for a child to cope, not only with the disease itself, but also with these unpleasant side effects; in some cases by the time a patient has reached their teenage years they’ve become so self conscious they’ve stopped taking their medication, even though they know it will speed up kidney failure and could result in their death.
“To approach this we’ve chemically modified the drug to target gamma-glutamyl transpeptidase, an enzyme on the surface of most cells that will carry the modified drug into the cell, so it becomes more like a magic bullet; directly getting inside those cells where it needs to be before the drug is released, increasing the therapeutic benefit.
“This means patients need less of the drug, as the dose is not being wasted through metabolism, and this also reduces the side effects.”

The research is being supported by national charity, the Cystinosis Foundation UK, who are funding Lisa’s PhD, and raised £14,000 to buy the university a piece of equipment which will drastically improve the effectiveness of her work.
Chairman of the foundation Roy Forsyth, whose 10-year-old daughter Lena has the disease, says: “We are committed to funding Lisa’s work and research on the drug. We realised she needed the HPLC (High-Performance Liquid Chromatography) equipment to make her work more effective and efficient. It’s crucial the research happens as quickly and effectively as possible; it will change lives.”

He added: “It’s outstanding for us to be involved in this quality of project and witness the results. If we can deliver a drug in the next 10 or 15 years then that will be fantastic. We are realistic and know these things take time, but we’re committed to the university’s research for the long term.”

Prof Anderson, who has been involved in the university’s cystinosis research for almost 12 years, said: “We are delighted with the help the foundation has given us, the HPLC equipment will improve the work we are doing.”
She added: “Initial work has shown that our prodrug approach can produce the required medicinal action; further experiments are ongoing to move from proof of concept to scientific evidence.

“In order to move these promising molecules forward towards clinical use, a systematic investigation of their mechanism of action, efficacy, formulation, pharmacokinetics and toxicity will be required before Phase I clinical trials can begin.”
Prof Anderson believes this can be done through a global collaborative group she is in the process of bringing together, initially made up of experts in the field of cystinosis from the UK, Belgium, France and Italy,
There is also evidence that cysteamine can be used in the treatment of other diseases, an area where Prof Anderson is encouraging further development.

 “Cysteamine is known to have therapeutic potential in the treatment of Huntington’s and Parkinson’s diseases, but is limited by its adverse properties and side effects. It also shows activity against the bacteria that causes malaria,” explained Prof Anderson.
She added: “Cystinosis patients also suffer from eye problems, for which the treatment is not ideal. We have designed another range of prodrugs specifically for ocular use and are evaluating their ability to treat this particular organ. Some of our pharmacy students are helping us with this research.”

Prof Anderson and Lisa recently travelled to the International Cystinosis Conference in Italy to present their findings before an audience of clinical experts and people whose lives are affected by the disease.
 “Meeting the families and children affected by this disease really pushed home how vital the work we are doing here is and made me even more determined to get results,” says Lisa, who graduated from Sunderland with a degree in Chemical and Pharmaceutical Science.

“The HPLC equipment will certainly help with the project; it’s new, reliable and dedicated to my work. Previously I had to share equipment, which was slowing the process down.
“It is challenging and hugely exciting being part of a project that could have a worldwide impact on people with all sorts of diseases.”

Attached files

  • Cystinosis sufferer Lena Forsyth, now aged 10

  • Professor Roz Anderson and PhD student Lisa Frost

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