Does multiple sclerosis consist of several different diseases? Dr. Anton Titov, MD. What do advanced MRI clinical trials show? You conduct MRI clinical trials in your multiple sclerosis research. I think all of the neurology listeners are well aware of this fact. Dr. Paul M. Matthews, MD. Several discoveries happened within the last decade. Work in multiple sclerosis at the Mayo Clinic was supported by additional work in Oxford and other institutions. It demonstrated that a specific multiple sclerosis syndrome was specifically associated with presence of an antibody. Dr. Paul M. Matthews, MD. This aspect of the MS syndrome was very distinct. Antibody was directed against Aquaporin 4. It is a protein that was found in the serum (blood). Moreover, it was found that this Aquaporin 4 antibody was responsible for the Oriental form of Neuromyelitis optica. There is a specific oriental form of the Neuromyelitis optica [NMO]. There is also the Caucasian form of Neuromyelitis optica. This antibody provides a unifying biomarker for this syndrome [NMO]. Much has been learned since then. Because it also has been possible to make animal models of Neuromyelitis optica. We really started to understand the pathophysiology of NMO relatively precisely. Dr. Paul M. Matthews, MD. I think this is the most prominent success for a precision medicine-based approach. Neuromyelitis optica is a subgroup of syndromes. They all had previously been considered to be multiple sclerosis. Now Neuromyelitis optica has been defined as a specific disease entity. It is now considered to be quite distinct. Neuromyelitis optica responds to multiple sclerosis medications differently. NMO has different prognosis. Dr. Anton Titov, MD. It occurs in different patient populations. Let’s look at what is left of the broader multiple sclerosis syndrome. This is also clear. The patients with different HLA genotypes are susceptible to multiple sclerosis severity at different levels. For example, the HLA 1501 haplotype is associated with a more malignant progression of the multiple sclerosis. Increasingly, we hope to find other strong genetic markers of multiple sclerosis. Dr. Anton Titov, MD. This may help us to stratify patients with multiple sclerosis. Then we can begin the path towards personalization of treatment. Dr. Paul M. Matthews, MD. Finally, I would note that the path to personalization of multiple sclerosis treatment is likely not simple. Precision medicine treatment of multiple sclerosis is not going to depend on a single biomarker. I believe that the NMO case was very fortunate. But it probably is going to be less usual. Multiple risk factors will likely need to be taken into account for personalization of MS therapy. Dr. Paul M. Matthews, MD. There are genetic, environmental, lifestyle factors that affect multiple sclerosis. We have to recognize the influence of latitude, vitamin D levels, smoking, and other high-risk behaviors. Genetic susceptibility factors for multiple sclerosis are also important. All of this, will help us better assess multiple sclerosis patients on first visit to doctor. Then we can begin to provide patients with information about prognosis. Dr. Paul M. Matthews, MD. Finally, I think that this personalization can be enhanced substantially by the use of special MRI. MRI imaging provides us a direct view of the pathology as it evolves. Serial imaging clinical trials are able to document the rate of change of T2 lesion load in the brain. MRI allows us to observe the accompanying damage. Damage occurs with T2 lesions expressed in terms of measures of demyelination and axon loss. MRI also measures brain atrophy. Dr. Anton Titov, MD. Altogether serial MRIs give us a sense for the severity of the pathology in multiple sclerosis. I hope we will use it for precision medicine treatment. MRI will lead us to algorithms to allow to stratify patients much more precisely within the first year o multiple sclerosis appearance. Dr. Paul M. Matthews, MD. We can separate patients into those who really need very highly effective therapies. We can also identify patients with multiple sclerosis. They may benefit equally well from therapies with the lower anti-inflammatory efficacy in the group overall. But potentially such medications can have better safety profiles. Clearly this is one part of the precision medicine. It is the predictive abilities at the early stages of multiple sclerosis to stratify patients. Some patients would need more aggressive multiple sclerosis therapy. Dr. Paul M. Matthews, MD. Other patients will require less aggressive therapy. Yes, I think that’s true. In precision medicine we want to have a better explanation to an individual patient what is a likely prognosis. Then the patient has to decide what is the best benefit-risk profile of multiple sclerosis treatment. Dr. Anton Titov, MD. Patient with multiple sclerosis can choose from the broad range of medicines that we now have. Because we are in the fortunate position now. We have many medications against multiple sclerosis. They really do have such a broad range of efficacy and safety characteristics.
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