In the latest issue of the Lancet Neurology journal, Professor Alan Thompson, Consultant Neurologist at the National Hospital for Neurology and Neurosurgery and Dean of the UCL Faculty of Brain Sciences, highlighted some of 2016’s research discoveries in MS.
Radiologically isolated syndrome
He highlights research that followed people with “radiologically isolated syndrome” over many years. Radiologically isolated syndrome implies the presence of MRI brain abnormality (such as lesions similar to those seen in MS) without the presence of clinical symptoms typical of MS. This study was performed at 22 clinical sites in 5 countries and was led by investigators at Mayo Clinic in Rochester, Minnesota. The results showed that from 453 people who presented with radiologically isolated syndrome, 128 evolved to symptomatic MS over a follow up of approximately 6 years and 15 of those evolved to primary progressive MS. This is the same rate as the progression in general MS population and may suggest that, in future, radiologically isolated syndrome could be considered as another subtype of MS.
Another study in this report is the work by an MS group at Queen Square in University College London. Brain and spinal cord cells, which are affected by MS more than other cells in our bodies, are dependent on oxygen. In this study Prof Kenneth Smith and colleagues found that lesions in the spinal cord of an animal model of MS are seen in areas where there is a deficiency of oxygen, and that this can be delayed or reversed by delivering oxygen to the tissue. This has potential consequences for developing future drugs that can change the MS lesion environment in the brain or spinal cord by delivering oxygen.
Professor Thompson highlights another study, from the MS centre of Paris (Sorbonne University). Some MS lesions may be reversed over time in a process called remyelination. Remyelination, however, only happens in some people and doesn’t affect all lesions. People who have a higher potential of remyelination may have a better chance of benefitting from specific MS treatments. Advanced brain imaging by a technique called Positron Emission Tomography (or PET) may visualise this process. Dr Benedetta Bodini and colleagues found that this method of brain imaging can distinguish people with MS who have a higher remyelination potential. This advanced imaging method may in future be used to test drugs that have the potential to reverse brain lesions in people with MS and repair damage in the brain.
Elie Dolgin from the Nature journal emphasised important trial achievements in 2016. He discusses the success of the ocrelizumab trial and the expected regulatory approval in 2017. Ocrelizumab is an intravenous infusion treatment. It works by targeting B cells (a type of immune cell) which helps to reduce the immune response by stopping these cells from attacking and damaging myelin. It is expected to be approved by USA Food and Drug Administration in March 2017 for people with primary progressive MS.
The success of the ocrelizumab trial is, in part, due to the lessons investigators learned from the failure of previous trials of a similar drug called rituximab. In the rituximab trial, investigators realised that when looking at everyone together, the drug had no positive effect. However, they noticed a positive effect on people with primary progressive MS who were younger and more likely to have active disease. The ocrelizumab trial included this population and therefore it may only be effective for a subset of people with primary progressive MS.
Another successful drug trial for secondary progressive MS was for a drug similar to fingolimod, known as siponimod. Similar to ocrelizumab, the highest effect was observed in patients with early secondary progressive MS and those who were younger, with lower neurologic disability (assessed by a scale known as expanded disability status scale or EDSS), and lower MS duration.