Ambitious new studies will give new insights into Parkinson’s, addiction and the immune system

Three ambitious new research programmes, which aim to deliver a step-change in our understanding of disease by using human volunteers in experimental studies, have been funded as part of a £60m investment from the Medical Research Council (MRC).

The latest phase of the MRC’s Experimental Medicine Challenge will provide new insights into the biological mechanisms of Parkinson’s disease, reduced immunity in the elderly and the way the gut and brain interact to influence addictive behaviour.

By studying these conditions in people, scientists will gain a detailed understanding of how disease takes hold and progresses within the body. This may help them to identify new opportunities to intervene with medical treatments and researchers can also use their findings from human studies to work backwards and design better experiments in the lab.

Commenting on the awards, Life Sciences Minister George Freeman said:

“Understanding how disease really works in humans is crucial in generating new treatments and medicines. The more we discover about disease the more we know how and why different patients respond in different ways to different diseases and drugs: unlocking a new age of preventative and personalised medicine. Through the NHS’s unique strengths as a national healthcare system, with 50 years of disease and drug data, we are leading the world in this exciting field. And attracting billions of investment in new treatments to benefit NHS patients.”

Professor Sir John Savill, Chief Executive of the MRC, added:

“While scientists learn a great deal from molecular, cellular and animal studies, often it’s only through in-depth human studies that we can effectively untangle complex diseases. There have been huge leaps in technologies such as high-speed genomic sequencing and lab-grown human tissue that enable us to carry out ever more sophisticated clinical studies. This will ultimately allow us to translate research into new treatments and diagnostics faster, cheaper and more safely.”

Details of the three projects, which represent a total investment of £6m, are outlined below:

• Why are we more susceptible to infections as we age?
  A project led by Professor Arne Akbar at UCL will investigate whether damping down the ‘background’ level of inflammation in older people could help their immune system fight off infections, and improve the effectiveness of vaccines in this population. As we get older, our immune system isn’t as good at combating viruses and bacteria and we become more susceptible to diseases as a result, even ones we’ve previously built up immunity to. Vaccines are also less effective in the elderly, but the reasons why are not fully understood. It is thought that a persistent low-level of inflammation in older people could play a role. In this study, young and old volunteers will be exposed to safe levels of a foreign pathogen so that scientists can study in detail the differences in how the immune system responds as we age. They will then use a drug to block the low-level inflammation that exists in the elderly participants to see if this helps to improve their immune response.
• Could drugs designed to suppress appetite also reduce the urge to smoke and drink?
  Professor David Nutt and Dr Tony Goldstone at Imperial College London will lead a series of experiments to see whether suppressing the appetite, using naturally-occurring gut hormones, could also reduce cravings for addictive substances such as cigarettes and alcohol. Studies in rodents have shown that increasing levels of hormones that normally make us feel full after eating not only reduce appetite for food, but also alcohol, nicotine and other drugs. It is thought that the effect comes about by interfering with the ‘reward’ mechanism in the brain that makes us derive pleasure from these behaviours. The ultimate aim is to develop new therapies to help people to tackle their addictions, which would have a hugely positive impact on their health and would reduce significantly the burden that these issues place on society.
• Slowing progression of Parkinson’s disease
  A third project led by Professor Anthony Schapira at UCL will investigate the role of a genetic mutation in the development and progression of Parkinson’s disease. Parkinson’s is the second most common form of neurodegeneration, after Alzheimer’s, yet there is still a lot we don’t understand about the disease and its causes. Mutations in a gene called GBA increase the risk of developing the disease by 20-30 times and are present in around one in 10 Parkinson’s patients. It’s therefore possible that a drug which replaces some of the function of this gene, by boosting activity of an enzyme, could slow progression of the disease in patients with this mutation. This project will follow 200 patients with the GBA mutation to see how their signs and symptoms can signal biological progression of the disease. They will also test an existing drug, which was developed originally to treat a different condition (Gaucher disease), on patient cells and in mice to lay the groundwork for human trials of a new therapy for Parkinson’s.

The MRC plans to commit a total of £60m to Experimental Medicine over three years.