Medical Research Council (MRC)/ MND Association Lady Edith Wolfson Senior Clinical Research fellow, Dr Martin Turner writes about recent developments in his BioMox study.
My first ever blog. I decided to share developments in ‘BioMOx’ – the Oxford Study for Biomarkers in MND, which has been funded through the MND Association’s pioneering Lady Edith Wolfson Fellowship scheme (in conjunction with the Medical Research Council).
Between 2009 and 2013, over 70 people living with MND (and some healthy people of similar age for comparison), took part in a new type of patient-based study. Men and women of all ages (from 28 to 86), some with primary lateral sclerosis (PLS) as well as a range of the more common amyotrophic lateral sclerosis (ALS) types, all gave up their time to attend for a day or two of tests in Oxford.
They underwent advanced MRI scanning of the brain, which provided detailed maps of structural changes not normally visible on standard hospital MRI scans, as well as information about how different networks of brain cells talk to each other. We also looked at how their eyes followed targets around on a screen using an infrared eye-tracking camera. They also provided a blood sample, and the majority of them even allowed me to take a sample of spinal fluid. Crucially the patients agreed to try to come back and have it all done again every six months. This type of natural history study had been lacking, yet is essential to tailoring future MND treatments to individual variation.
The scans and samples were studied for markers that might be used to speed up diagnosis, classify different types of MND and assess responses in future drug trials – a global quest for what are called biomarkers. And several candidate biomarkers have emerged. We have an MRI marker of loss of structural integrity of key motor system pathways (including the bridge between the two halves of the brain), and a chemical correlate of damage that we can measure in a blood test. The challenge now is to apply these findings to those who have the earliest symptoms of MND, perhaps in the process of undergoing tests requested by their neurologist.
Many patients know only too well that it currently takes several months, sometimes years, to make a firm diagnosis of MND. This is because there is no positive test for MND, only tests to rule other conditions. We envisage that perhaps a 20-minute advanced MRI scan of the brain, plus a blood test and simple eye-tracking measurements might form the basis of a panel of new tests that not only help to diagnose MND more quickly, but also provide a unique signature for an individual against which to test new treatments and decide sooner if they are working or not.
Working with colleagues in the USA
Another exciting aspect of BioMOx is that we are working in partnership with the University of Miami USA, where Dr Michael Benatar runs a ground-breaking project called ‘pre-FALS’. This project is studying the close relatives of rare patients with hereditary forms of MND (5-10% of total MND cases), to see if it possible to detect very early changes. Dr Benatar has gathered participants from all over the USA.
Every year they undergo muscle and blood tests, as well as some advanced MRI scans. We have started to fly some of them over to the UK for 5 days, to undergo parallel, additional studies in the UK. There are also efforts underway to establish a registry for UK relatives of those with inherited MND, so that we can start to study people closer to home. Find out more here.
Powerful brain scans
Our tests are going to involve an extremely powerful MRI scanner, one of only two such machines in the UK, which we hope will provide unrivalled detail of the structure and function of the brain and spinal cord. The magnetic field strength is extremely high (7 Tesla, which is 4 times as strong as typical hospital MRI scanners), and it requires a half-metre thick copper-shielded room to prevent the magnetic field reaching into neighbouring counties (yes, counties), as well as its own electrical sub-station to stop the lights dimming across Oxford every time we scan someone.
We are also using a very sensitive tool called magnetoencephalography (MEG) to measure brain waves at more than 300 points on the scalp surface to see how the motor system operates differently in those at risk of, as well as those living with MND. Exciting times indeed. The pace of scientific change in MND has never been greater, and so too the hope of a major breakthrough in treatment terms. Biomarkers will be an essential part of capitalising on the giant leaps being made by my scientist colleagues in laboratories around the globe as well as in Oxford, who are studying nerve cells in dishes, and genetic material in test tubes.
As our results help to move the prospect of new treatments for MND closer, I also see BioMOx as a demonstration of the power and unique value of patient-based research. There is no better model of this incredibly complex disease than the human, but it is only the courage and altruism of people living with MND, and their healthy volunteer friends, that can drive us towards the ultimate goal of improved therapy.