Researchers awarded vital funding to explore treatment to slow rare liver disease

LifeArc and PSC Support have jointly awarded £948,774 for new research into primary sclerosing cholangitis (PSC) – a rare disease where the body attacks its own liver, causing inflammation and scarring of the bile ducts.

The national study, led by Dr Palak Trivedi at BHP founder-member the University of Birmingham, is called FAecal microbiota transplantation in primaRy sclerosinG chOlangitis: The FARGO trial. The aim of the study is to explore the potential of a new treatment to slow the progression of PSC and improve the quality of life for patients.

PSC is a rare liver disease where the body attacks itself, causing inflammation and scarring of the bile ducts and liver. This causes bile to stop flowing properly, leading to repeated infections, liver failure and, in some cases, cancer. In 80% of people with PSC the body will also attack the bowel, which can lead to inflammatory bowel disease (IBD).

The combination of the two conditions results in a 15-30% lifetime risk of bowel cancer, and patients require a colonoscopy every year to look for this complication. PSC affects approximately 3,600 people in the UK. The condition can develop at any age, but has a particular impact in people under 40 years.

At present, the treatment of PSC is focused on managing the symptoms, not treating the cause. Unfortunately, there is no cure, nor any medication that has been shown to improve survival. Liver transplantation is the only lifesaving treatment. Although a very rare disease, PSC accounts for 10-15% of all liver transplants performed in the UK and is now the leading reason for transplantation in several European countries.

Transplantation is risky and costs around £1m per patient (including aftercare). Moreover, PSC returns in around 30% of people who have had a liver transplant.

The team, led by researchers at the University of Birmingham, has one of the largest PSC research programmes globally, with a dedicated PSC-IBD clinic as part of the Centre for Rare Diseases. The research team is partnering with PSC Support, the leading patient organisation for people living with primary sclerosing cholangitis, which has a wealth of experience working with medicines’ regulators on drug development for this condition.

Through this partnership the team aims to explore the potential of a new treatment to slow the progression of PSC and improve the quality of life for patients.

It has been shown that the makeup of gut microorganisms in PSC are different to that found in people without liver and bowel inflammation, and that this is associated with many abnormal immune functions, which may be a driver of disease development. The Birmingham research team will trial a novel treatment called faecal microbiota transplantation (FMT), which involves taking stool from the gut of healthy donors, refining it in a laboratory, and transferring contents to the bowel of people with PSC to reverse the imbalance of gut microorganisms.

Early research has shown that FMT is effective and safe in treating IBD. This grant, which is jointly awarded by the LifeArc philanthropic fund and PSC Support, will enable the team to accelerate and scale up their research to answer the key questions that will allow them to translate this experimental treatment, from idea to direct patient benefit across the UK PSC population.

Dr Trivedi, Associate Professor and Consultant Hepatologist at the NIHR Birmingham BRC said: “LifeArc is a self-financing charity that advances promising life science ideas into life-changing solutions for patients, particularly those living with a rare disease. I am delighted that they have chosen to support such a novel, bespoke and distinctive clinical trial, alongside the necessary translational work needed to better understand how PSC develops and progresses.

“We will test the safety and long-term effects of FMT to treat people with PSC. In parallel, this study will really help us to understand which specific consortia of gut microbes are most important, and how this information can be used to enhance the product for large scale rollout.”

Researchers will randomly allocate individuals with PSC to receive either FMT once a week for 8 weeks (group 1), or placebo (an inactive FMT equivalent; group 2). Each group will continue to receive routine standard of care for symptoms and treatment for their IBD.

Both groups will be observed for another 40 weeks, meaning the trial will run for 48 weeks. The team will then measure how successful the treatment has been in improving liver blood test results, the burden of scarring in the liver, activity of IBD and quality of life.

“Our study will lay the foundation for future work on a larger scale, with a view to making FMT available on a more global scale,” added Dr Trivedi. “In parallel, PSC Support will work with the wider study team, to support delivery of FMT as a treatment after the trial has finished.

“This will include writing and submitting the necessary trial documents to the UK medicines’ regulatory agency (the MHRA), which is a necessary step to broaden access to new treatments for people living with the disease.

“Should our trial deliver a positive efficacy signal, then PSC Support are ready to lead the conversation and advocate for patients to access FMT as early as possible. We expect patient benefit within 5-7 years after completion of this work and are working with the University of Birmingham Enterprise and Drug Discovery teams to achieve this goal.”