Decoding our system to fight disease

In the age of genomics and big data, our systems could hold the key to fighting disease.

Multiple sclerosis (MS) is the second biggest cause of disability in young people in the EU. It is a chronic disorder of the central nervous system where the immune system attacks the cells that protect nerves.

At the moment, there is no cure. However, a new way of understanding disease called systems medicine could provide answers where traditional drug discovery has failed.

The problem is that researchers are running out of easy-to-access new molecules to test against diseases, meaning that there are fewer and fewer potential drugs in development.

‘We have a technical crisis in the pharmaceutical industry because the model that produces drugs is more or less exhausted,’ said Dr Pablo Villoslada, a researcher at the August Pi i Sunyer Biomedical Research Institute (IDIBAPS) in Barcelona, Spain, and founder of Bionure, a biotech company developing drugs for MS.

‘It is a high priority to find new ways to identify new therapeutic processes and new drugs.’

Normally, drug discovery involves picking out a molecule in the body that could have an impact on a disease, and then trying out hundreds of potential drugs on it to see what happens using computerised machines.

However, Dr Villoslada and his team have turned the whole process on its head. Instead they take blood samples from MS patients and healthy people. Then they provoke the white blood cells of each group, and see what differences there are between the way they behave.

Data

They feed the data into computer systems which measure it against what is already known.

‘We can run a model to see which proteins we can target in order to restore the system to a healthier state,’ said Dr Villoslada. ‘This is our approach to drug discovery.’

By identifying target proteins early on and allowing researchers to check the effect that any drug is likely to have on the immune system as a whole, this approach has the potential to make drug discovery more efficient.

The work was done as part of an EU-funded research project, known as CombiMS, which finished at the end of last year. Now they are looking for additional funding to continue the work. The researchers hope to extend the model to help improve predictions of disease progression in patients.

Systems medicine is also being used to tackle diseases such as ulcerative colitis and Crohn’s disease, which are commonly known as inflammatory bowel disease (IBD). IBD affects more than 2.2 million people in Europe.

Using similar methods to the CombiMS project, researchers on an EU-funded project known as SysmedIBD are developing complex models by combining data from laboratory work – on human samples and animal models – with mathematical models based on current knowledge of the inflammatory process.

A key part of the SysmedIBD project is analysing existing patient data to create the different patient groups. The researchers are relying on a long-running group of almost 3 000 patients from the Netherlands, many of whom were first registered in 1991.

They are using computer programmes to classify and group anonymised patients from the Netherlands data based on factors related to their IBD.

Tell-tale molecules

They hope to predict tell-tale molecules – known as biomarkers – that could classify IBD patients. New patients will then be compared with the classified patient groups, and assigned to one of the groups.

‘The aim is to get the patient in the right group early and then suggest the best treatment for them,’ said Professor Werner Müller, from the University of Manchester, who coordinates the research.

The patient data also includes information on the effectiveness of treatment strategies, which can be used to suggest the best course of action for each group.

Prof. Müller hopes that the techniques and the model they are developing will also apply to other diseases that involve chronic inflammation, such as certain types of arthritis, psoriasis, various liver diseases and MS.

The CombiMS project has the same potential. ‘We are studying the immune system, which means (our research) can be readily translated to all immunological and autoimmune diseases,’ Bionure’s Dr Villoslada said.

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