Posted by Sheila Silvas on Jun 17, 2016
Interview with Research Dr. Daniel Miller on June 2 2016
Sheila had the pleasure of meeting with Daniel G. Miller, Geneticist at Seattle Children’s Hospital, and Associate Professor at the University of Washington. Dr. Miller and colleagues from the University of Rochester, the University of Washington, and Seattle Children’s Hospital recently published a cross sectional study of two independent groups of people with FSHD, and identified serum biomarkers. The landmark study was published in the journal Neuromuscular Disorders.
See resulting paper published in Neuromuscular Disorders.
Silvas: What was your intended purpose for doing this study?
Miller: More than ten years ago I encountered a patient with FSHD and found that there was very little research, few ideas for treatment, and most importantly, no cure for this devastating disease. About the same time, Terry Colella, president of Friends of FSH Research, began raising money for FSH research. Her organization which has now funded many FSHD studies, seeded the necessary funds to get FSHD research off the ground in the Seattle area. These funds have allowed Seattle researchers to leverage projects for funding from the National Institutes of Health (NIH) and have resulted in important discoveries about how FSHD mutations cause muscles to be sick.
We now need practical, quantitative methods to measure disease progression and or regression so that the effectiveness of a particular treatment can be measured in a clinical trial. This study was designed to find proteins in the blood that correlate with disease status so the effect of possible FSHD treatments could begin to be evaluated.
Silvas: Was the goal of the research to look into the pathology of FSHD or more for measuring the burden of FSH disease?
Miller: The goal was to find a way to measure and quantify the rate of disease progression. We need a way to test whether therapies are working by first creating a start point or baseline level of FSHD severity. Then we can determine if proposed therapies make a significant difference to the severity level of the disease. Without biomarkers, FSHD severity is measured by testing the strength of the individual muscles which can be a fairly insensitive measure of disease progression. Strength changes are sporadic in some individuals with periods of time with no perceptible difference in strength, and periods where complete loss of mobility in one arm can occur over a short period of time. A future therapy may appear to be working because the individual hasn’t lost muscle strength but we wouldn’t know if it was because of the treatment or simply the variable nature of the disease without a true quantifiable measurement of disease burden before and after the start of the treatment.
Silvas: What role will these biomarkers play in future research? What do they reveal?
Miller: Generally speaking the biomarkers turned out to be the products of muscle breakdown. In combination with MR imaging, and assessments of strength and movement the biomarkers will allow for quantification of the disease severity. These biomarkers should allow for a close up, numerical, view of an individual’s disease progression. Further validation is needed but I think they will be useful in clinical trials that test the efficacy of future therapies.
Silvas: What does this information mean to a person with FSHD?
Miller: It means we have one more tool in the toolbox for testing logical treatments that we hope will halt or reverse the disease process. Levels of these proteins may also be helpful for disease prognosis in the near term. For example, with further study we may be able to determine if someone with FSHD is likely to have a period of significant strength decline or whether they are in a period where the disease is relatively inactive. I think these biomarkers will be most important for testing therapies which hopefully will affect everyone with FSHD.
Silvas: How does this study contribute to the future studies surrounding FSHD?
Miller: This study provides another analysis tool for people with FSHD. As researchers, we need sensitive techniques to measure the small differences in muscle destruction that occur over relatively short periods of time. The shorter the time that it takes to perceive a difference in disease severity, the more treatments that can be tested quickly to find the ones that will make a difference in the lives of people with FSHD. Time is very important here because people are getting weaker with each passing day. We don’t want to waste one second on treatments that may seem promising at first but don’t ultimately change the outcome.
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