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Dr John Corboy Forecasts Promising Developments in Multiple Sclerosis


Rebooting the immune system is an exciting approach, noted John Corboy, MD, professor of neurology, University of Colorado Denver, School of Medicine, and co-director of the Rocky Mountain MS Center at Anschutz Medical Campus.

Investigating rebooting the immune system by using highly effective therapies is a novel approach currently under investigation for patients with multiple sclerosis (MS) with aggressive disease, noted John Corboy, MD, professor of neurology, University of Colorado Denver, School of Medicine, and co-director of the Rocky Mountain MS Center at Anschutz Medical Campus.


What exciting developments are on the horizon in multiple sclerosis research that can benefit older patients?

There are a number of studies that are presently underway, which are directly assessing the potential impact of either medications or supplements, antioxidants, and other things in progressive MS patients. One recently reported study not yet published is the biotin study, high-dose biotin and progressive MS. A preliminary study suggested that it may be beneficial, in fact even improve function in a small but significant minority of patients with MS. Unfortunately, a larger trial did not confirm that.

But there are other studies, as well. They’re studies alpha lipoic acid, and there's studies with simvastatin, one of the cholesterol agents. There have been studies with with ibudilast, a medication used to treat asthma in Japan. It's not clear if they'll be further studies with that.

There's also a population, or a type of agent, called BTK inhibitors (Bruton's tyrosine kinase inhibitors), that have the potential, especially as small molecules, to not only act in an anti-inflammatory component, similar to that which we see with some of the B-cell therapies—such as ocrelizumab, rituximab, or now ofatumumab—but [that] also may have potential effects separate from that that would have potential benefit for individuals with progressive MS. So maybe sort of dual actions that would be potentially beneficial.

And there are a number of others as well. So I'm excited for those because I think there are a number of things that are relatively close that potentially could be beneficial.

On the other end of spectrum, we're about to begin shortly—soon as everybody can get back to doing all their regular rounds of clinical research—a study at the other end of the spectrum for people with very aggressive and highly inflammatory disease, with relapses and scan changes in spite of the usual therapy. And that's the BMS [Bristol Myers Squibb] trial, the best-available-therapy trial, in which we'll look at high-dose immunotherapy with Cytoxan and others to ablate the immune system, followed by autologous hematopoietic stem cell transplant with the hopes of rebooting the immune system, if you will, for people who are primarily younger with highly aggressive disease. This is a relatively smaller population, overall, but for these individuals, MS is not just an irritation, it's devastating in very young people. And so the hope is that this will give us information as to the utility of this approach in comparison to best-available therapy, which is the highly effective monoclonal antibody therapies, which will be the control group for this outcome.

So I'm excited by that because I think it will be the greatest test today, if you will, of the concept of rebooting the immune system and using highly effective therapies as soon as it is noted that people have aggressive disease. And using the 2 primary approaches, one would be sort of this almost chemo-therapeutic approach followed by stem cell rescue compared to best available medical therapy that we have now. And I think for that small subset of patients that will be an incredibly important study. So that excites me as well.

And there are a number of other things that are really incredibly important. I'm interested to see—I have not seen the data and I'm not sure if it'll be at the meeting this year—data looking at neural progenitor cells infused into the spinal fluid. And there's a very small study that's underway—again, I don't know if they’re going to be reported here—looking at whether or not the proof of principle that the cells can actually be taken up and actually have a physiologic function, if that is the case, [or] the potential of neural progenitor cells infused directly into the spinal fluid, which has the potential of repair either directly or, more likely, indirectly by stimulating repair from cells already present inside the central nervous system.

There’s a proof-of-principle, very small study, to show that these cells can survive if infused and that they would potentially have a physiological effect that is measurable. If that is true, then the potential is there that a larger study could be done to show that they're efficacious and would offer the potential, again, potentially for progressive patients for repair, where individuals perhaps would have some fixed deficit or even worsening deficit that might be benefited in a positive sense by improvement. So I'm excited by that kind of approach, because I think it's novel.

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