10:24pm Friday 10 July 2020

Work begins to develop life-saving liver treatment

Primary Biliary Cirrhosis (PBC) is thought to affect 20,000 people in the UK – currently, around 30% of patients with this condition do not respond to the only drug treatments available and their only option is a transplant. The new study led by Newcastle University and funded by the Medical Research Council (MRC), will recruit half of those affected in the UK, 10,000, at sites around the country.

Early studies from the research group have already shown that people with PBC are less likely to respond to treatment if they are younger – under 50 – and male.

This new collaboration, between scientists, doctors and patient groups, will provide a better understanding of why some patients respond to treatment and some don’t; work with pharmaceutical companies to develop new drugs; and design a national protocol to streamline treatment across the UK. This will help ensure that, in future, patients receive the right type and level of treatment depending on the severity of their disease and individual biological make-up, and determine whether that should be at their GP or in a specialist centre. This approach is known as “stratified medicine”.

Announced today by David Willetts, Minister for Universities and Science, and receiving around £5 million from the MRC, the research involves the universities of Birmingham, Cambridge, Newcastle and Imperial College London. It also involves all NHS hospital Trusts and 11 companies including Intercept Pharmaceuticals, Inc, INOVA Diagnostics Inc and Lumena Pharmaceuticals.

David Willetts (pictured above with PBC patient Fiona Hale) said:”This study has enormous potential for sufferers of this life-threatening liver disease. By bringing researchers and industry together, we can get a clearer picture of why people respond differently to treatment and develop more effective, targeted drugs. This will dramatically improve quality of life for patients, reduce the number liver transplants and drive growth in the pharmaceutical sector, supporting the Government’s life sciences strategy.”

Leading the collaboration Professor Dave Jones, a world-recognised expert in chronic liver disease from Newcastle University said: “Patients diagnosed with the condition over the age of 70 have a 95% chance of responding positively to treatment. However, if they are under 50, then there is only a 50% chance of the medication working. For these younger patients who it does not work for, they are likely to need a transplant or may die which is why this collaboration is so important.

“Working with internationally established pharmaceutical companies and researchers around the UK we will be able to study the differences between the groups of patients and develop new drug treatments which work for them.”

Dr. David Shapiro, Chief Medical Officer at Intercept Pharmaceuticals and Chairman of the collaborative bio-pharmaceutical group in the consortium noted: “The UK-PBC consortium is unique; there are no other nationwide PBC research groups in the world that can conduct clinical research and develop improved care pathways for patients across a whole country.  This is a significant advantage when trying to develop new therapies for a rare disease and, accordingly, many researchers across the world will wish to collaborate with the consortium. This should speed the time that better therapies can become available to UK patients.  Already significant additional grant money has been committed by companies to provide more support to the group.”

In PBC, for reasons not yet fully understood, the immune system turns upon itself and gradually damages the bile ducts in the liver. Eventually this damage leads to a blockage that obstructs the flow of bile which builds up to a dangerous level, causing liver scarring known as cirrhosis.

If not treated or patients do not respond to treatment, the liver can become damaged to such an extent that it no longer works which can lead to liver failure and can be fatal. Liver transplantation is then the only option.

Currently there is no cure but it can be treated by a medicine called ursodeoxycholic acid which is known as “urso”. One of the areas of research for this collaboration will be why some patients respond well to this treatment but others do not. With the help of patient groups, 6,000 people have already been recruited for the study.

The MRC has invested £5 million in the collaboration investigating why different patients with the same diagnosis respond differently to treatments. The collaboration will deliver a better understanding of the mechanisms behind the diseases which will one day enable doctors to prescribe drugs and therapies that are tailored to an individual’s biological make-up, vastly improving their chances of getting better and reducing their risk of experiencing serious side-effects. Stratified medicine is a completely new approach to scientific research and medical care. Grouping patients into ‘strata’ based on differences in the way they experience a particular disease and how that affects their response to treatment.

Dr Des Walsh, Head of the MRC’s Infections and Immunity Board and the lead of their Stratified Medicine Initiative, said: “Medical treatment has always been targeted to individual patients based on their symptoms and diagnostic tests. However, not all patients respond to treatments. Huge advances in human biology in recent years mean we can now go even further in identifying differences between individuals with the same diagnosis and begin to understand the reasons why. This has the potential to transform the way we diagnose and treat PBC and a wide range of common diseases, ensuring that patients receive the drugs that will work best for them.”

Before this can happen, groups of patients must be studied to understand what it is about their genetic and physical make-up that determines these differences.

The patient’s perspective: Fiona Hale from Whitley Bay

Fiona (pictured above with Minister, David Willetts) began noticing the symptoms when she was 38. She was already on the alert because she had been found to have the antibody for the disease when she was 28, although at that point it was hoped it would not progress. And despite PBC not being an inherited condition, her mother had been diagnosed with the condition and had a liver transplant.

Fiona describes the condition as affecting every aspect of her life: “PBC means I have fatigue and memory and concentration problems. It’s hard to describe how the fatigue feels, it is like walking through treacle, or as if my batteries are flat – I can’t gear up for things, and I can’t keep going for long. I really have to pace myself. If I am busy one day, it will take me a couple of days to recover. I do have good days, but it’s unpredictable, and on a bad day I really can’t do anything much. I don’t look ill, so that can be hard for people to understand.

“Until now, PBC has been seen as something mainly affecting older women. But now there is a better understanding that people like me who are diagnosed younger often do worse. The current treatment for PBC is urso, but it only slows down the process. It’s not a cure. Not everyone responds to urso – particularly those of us diagnosed at a younger age. At the moment there is no other treatment. And even if urso controls your liver function, there is nothing available for the fatigue. This new initiative is really exciting, especially if it can find new treatments for PBC and its symptoms.

“PBC has a massive impact on my family life – my 7-year-old daughter and my partner. I used to be very active. Now I do my best, but I struggle to feel that I’m playing a full part in family life. I worry about how my fatigue impacts on my daughter. I’m lucky to have a very supportive partner.

“It has also changed my career, I used to run an operation in nine countries, but I couldn’t keep it up once I started getting symptoms. Now I’m self-employed and work from home, which gives me a bit more flexibility to rest when I need to. I’ve had to completely change my working life to adapt to the fact I have PBC. That has been really hard.”

FACT BOX:

Primary Biliary Cirrhosis is an autoimmune disease of the liver. It is not connected with drinking.

It affects one in 3,000 people

It mainly affects women – with nine women affected for every man. The condition usually occurs in people ages 30 – 65.

Symptoms include; chronic fatigue, itching of the skin, sore joints, easy bruising, dry mouth and eyes and jaundice (which is a sign of the disease progressing.)

It is thought to be more common in North East England, Scandinavia and Scotland though it occurs worldwide.

Key Facts:

  • Newcastle University is a Russell Group University
  • We rank in the top 20 of UK universities in The Sunday Times 2013 University Guide
  • Amongst our peers Newcastle is:
    • 10th in the UK for student satisfaction
    • Ranked 8th in the UK for Medical research power
    • In the UK’s top 12 for research power in Science and Engineering
  • 95% of our students are in a job or further training within six months of graduating
  • We have a world-class reputation for research excellence and are spearheading three major societal challenges that have a significant impact on global society. These themes are: Ageing and Health, Sustainability, and Social Renewal
  • Newcastle University is the first UK university to establish a fully owned international branch campus for medicine at its NUMed Campus in Malaysia which opened in 2011
  • Our International students put Newcastle University in world’s top 12 (ISB 2011)

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