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From bedside to bench to bedside: Derisking MS research


 

REPORTING FROM ACTRIMS FORUM 2019

– Rhonda Voskuhl, MD, delivered the Kenneth P. Johnson Memorial lecture at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. In an hour-long talk, Dr. Voskuhl outlined her research approach, which she terms the “bedside to bench to bedside” strategy.

“My view has been that, when we start out research based on a molecule, we don’t really know for sure its clinical relevance. It’s kind of high risk, because you could go through a lot of work, for many years,” she said in a video interview. When work begins in vitro, the researcher runs the risk of proceeding from test tubes, to animal experiments, and then to people, “and then ultimately finding out that it’s not relevant,” said Dr. Voskuhl, director of the multiple sclerosis (MS) program and Jack H. Skirball Chair of Multiple Sclerosis Research at the University of California, Los Angeles.

“And so I just thought, to derisk this whole thing, I think I want to start at the end and then work backwards,” by choosing a physiologically relevant manifestation of MS, she said. “We know that there’s something there. ... All we have to do is figure it out.”

In iterative fashion, Dr. Voskuhl proceeds from the clinical observation, “which we know is true, and then go to the laboratory bench and figure it out by doing a lot of manipulation and isolation of one thing versus another.”

This process allows researchers to narrow down fruitful pathways before returning to the patient to conduct clinical trials using the one or two promising avenues discovered with bench science and animal models, she said.

“When you put this in the context of cell-specific and region-specific gene expression, to find disability-specific treatments,” Dr. Voskuhl said, this targeted approach helps address the fact that MS patients differ so much in their presentations and disease course.

“We know that, for example, the neuronal cells differ, and some of the neurotrophic cells differ from pathway to pathway; furthermore, what’s important is that oligocytes and astrocytes and dendrocytes have been shown to differ from one region of the brain and spinal cord to another. So these clearly would have different gene expression signatures, potentially posing different targets for treatment,” Dr. Voskuhl said.

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