Interview with CMSC Research Lecturer, Dr. Richard Rudick
By Kristin Jenkins

In an exclusive interview, Physician’s Forum spoke to the Consortium of Multiple Sclerosis Centers Research Lecturer, Dr. Richard Rudick, about achievements in MS and the future of clinical research. Dr. Rudick is Chairman of the Division of Clinical Research of the Cleveland Clinic Foundation, Cleveland, OH, and Director of the Mellen Center for Multiple Sclerosis Treatment and Research.

Physician’s Forum (PF): Where do we now stand in terms of understanding the cause of multiple sclerosis?

Richard Rudick MD: We are just beginning to unravel the underlying biological basis for multiple sclerosis. Some autopsy studies suggest there are different types of MS based on pathology in the brain and there’s even one study that suggests that how a patient responds to a specific MS therapy such as plasma exchange can be predicted by the type of MS the patient has. So at the moment, the classification of four MS subtypes is in the early stages of development.

 

PF: Might there be other subtypes of MS?

Dr. Rudick: I don’t really think we know how many underlying types of MS there could possibly be. One thing is for sure: MS is probably not the same entity biologically in one person as it is in another. This probably applies to a lot of the chronic conditions such as arthritis, diabetes and so on. At the end of the day, the affected target organs – the brain and spinal cord in MS, joint tissue in arthritis, the pancreas in diabetes – can only manifest failure in so many ways but there’s probably multiple different ways to get to that end stage.

 

PF: Why is the clinical course of MS so variable, patient to patient?

Dr. Rudick: I’ve seen identical twins with MS and one twin had a very mild form of the disease while the other had very severe MS. There are complex gene environment interactions, which determine not just the presence or absence of MS but the nature of MS, and how it affects the brain and spinal cord, how severe it is and probably how it responds to different therapies.

 

PF: Is neuromyelitis optica (NMO) considered a form of MS and if so, what significance does it have for better understanding of MS?

Dr. Rudick:  Neuromyelitis optica has been considered by many to be a form of MS but it’s different from regular MS because it tends to spare the brain and affect only the optic nerves and spinal cord. There’s a specific type of serum autoantibody in NMO which may attack the spinal cord and the optic nerves and which can be measured very specifically with a simple blood test. The serum autoantibody marker NMO-IgG appears to be the first biomarker of relevance to the MS world and it was discovered less than two years ago. A clinical assay that appears to be about 70% sensitive and 90% specific has been developed and you can send blood to The Mayo Clinic and request an NMO-IgG.

 

PF: What percentage of MS patients has this form of the disease?

Dr. Rudick: It’s a very small group that could be classified as NMO-MS, probably less than 5% or maybe even 2%. However, this form of MS represents the beginning of biologic classification and it’s the only real biologic classification that we currently have.

 

PF: What impact have advances in the field of genetics had on our understanding of MS?

Dr. Rudick: This is a whole new world that is moving ahead rapidly. It’s now possible to sequence 85% of the variability of the entire human genome in a single person for about $1,000. That’s amazing. How we handle that data and use it is another matter.

We’re learning how these genes go together and how they work and we’re finding that in complex diseases, they’re connected not to a specific gene or genes but to patterns of genes that have been inherited together as a chunk. So it turns out that genes aren’t randomly distributed through the generations; instead, there are chunks of genes, called haplotypes that tend to go together. We thought once we sequenced the [human] genome, we’d have the cure but it turns out that it’s not that easy. We now understand the process is much more complex.

The expectation is that over the next 10 years, we will classify the MS susceptibility and the MS variability based on our ability now to measure gene variability across the human genome. Then we may be able to predict individual variability including response to therapies. But I think that that’s really only the beginning because those susceptibility genes, whether there are five or eight—and the estimates are that there are a handful of genes responsible for susceptibility to MS—probably work by interacting with each other and with some exposure in the environment that we don’t understand yet, possibly viruses, which trigger the onset of MS.

 

PF: Do you think that there’s an infectious agent that triggers MS?

Dr. Rudick: I really think that we will have to [wait and] see. MS, in spite of all the progress we’ve made, is still a mysterious disease.  I’m not optimistic that we’re going to cure MS, but I’m optimistic that advances in biomedical sciences and in neuroimaging will soon make it possible to measure the pathology much more directly. Then, I believe we will be able to develop imaging biomarkers, which we can more specifically target with our therapies.

 

PF: How effective are current therapies?

Dr. Rudick: I think the drugs that we have are effective. When they’re used early in the course of disease, I think they slow and even stop the disease in some cases.

 

PF: What about the future of treatment, including TYSABRI (natalizumab)?

Dr. Rudick: The monoclonal antibody, TYSABRI, is an interesting new development in MS treatment because it’s a very highly-targeted therapy that has a profound effect on the inflammation that’s part of MS. Two patients out of roughly 2,000 MS patients treated with this drug developed PML, a normally innocuous brain infection that we’ve never before seen in MS patients. There are a lot of things we don’t know about TYSABRI, including how safe it is. The general expert opinion, however, is that this drug is a significant advance over existing treatment, that we need better treatment options and that TYSABRI will have a place in the therapy of MS.

So I think that there’s been real progress but we need to make more progress in the areas of primary and secondary progressive disease. For this, we need entirely new therapeutic approaches that are neuroprotective.

 

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