When dramatic advances in gene technology emerged, notably in the ability to sequence the genetic make-up of humans, there was "a great wave of enthusiasm". With it came belief new forms of treatment for diseases would quickly follow, Prof Stephen Sawcer recalls.
That equally applied to “autoimmune diseases”, conditions such as Multiple Sclerosis (MS) in which the immune system mistakenly attacks the body. Much progress has been made in identifying genetic factors linked to MS since, “but it hasn’t translated into an obvious treatment”, the Cambridge University-based researcher accepts.
People said “the problem is still there”, and as a consequence there was a loss of interest among research funding agencies, he notes, though an enormous amount of samples were provided by patients willing to participate in genetic studies.
Through a new alliance with Genomics Medicine Ireland (GMI), which uses that genetic sequencing technology in big research projects, he believes the necessary breakthrough is now realisable.
This will be greatly assisted by further improvement to gene sequencing technology, which is also rapid and deployable at little cost. When Prof Sawcer started out, it took him one year to process three small pieces of genetic material, known as “snips”, in 400 individuals.
“Now you can do 800,000 snips in an individual in 24 hours for $40. There has been a ridiculous change in the technology and it continues to get better and better.”
Immense resource
Critically, however, no one seemed to be interested in using "fantastic technology" and that immense resource provided by patients. That was until he got a call out of the blue from Dr David Kavanagh of GMI. "I was actually lying in the garden reading on a nice summer's day when he rang."
It became clear, he says, that someone in Ireland had realised there was unfinished research to be done and much to be gained by such work.
Sawcer brings a unique combination to the table in the form of more than 25 years’ research on genetic factors related to MS; a proven research track record and a large clinical practice as one the UK’s foremost neurologists – not to mention that large “biobank” of samples about to be added to by Irish patients.
As part of international collaborative efforts, his team has been very successful at identifying common genetic variants that influence the risk of MS, and is now trying to understand what those variants do.
“We have some good drugs but they are toxic and don’t work for everybody. With this research, GMI has hit the nail on the head in terms of working on a relevant population to a relevant depth,” he believes.
The critical factor in this case is “N”, the sample size in the research. The number of patients involved – in excess of 15,000 people with MS – “will enable transformational knowledge to emerge that will permit the development of rational therapies”, he predicts.
Correcting
When the new technology was emerging, researchers mistakenly believed it was simply a matter of identifying a gene involved in MS and correcting it. “It became clear it was not about changes in individual genes. It was about changes in the regulation of genes.”
It was about parts of the cell that decide which genes to use and how much genes are used. So MS, he explains, is not about “mutated genes”, more to do with an altered balance in normal genes that affects the immune system.
It is another indication of the complexity of the disease. People used to talk of “progressive MS” and “relapsing MS” as if they were different diseases. Sawcer does not agree with that distinction, though the disease has different dimensions and frequency varies in different countries.
Patients affected with the illness have episodes of “neurological upset” called relapses; such as blurred vision when the disease affects the optic nerve, or a weak leg or bladder if the spinal cord is attacked.
But there is a common “core issue” to the disease, though its effects can be variable, he says. Likewise, there aren’t particular forms prevalent in Ireland or Britain. “So it’s very likely that discoveries made here in Ireland will be translatable across the globe.”
