Quick Questions with Chief Scientific Advisor Dr. Jan Teller

This article originally appeared in the Dystonia Dialogue.

The DMRF leads a global research effort, grounded in the belief that the best service the Foundation can provide the dystonia community is to work every day toward improved therapies and a cure. Jan Teller, MA, PhD, DMRF’s Chief Scientific Advisor since 2006, recently commented on a handful of areas in which DMRF-funded investigators have made critical discoveries and progress.

DD: How would you summarize DMRF’s contributions to dystonia research over 40+ years?

JT: Almost half a century ago, DMRF spearheaded dystonia research as we know it today. DMRF initiated, supported, stimulated, and catalyzed essential scientific and medical efforts that created the modern dystonia field and gradually engaged critical institutions and participants in the process. Passion and unwavering commitment on the part of the Board of Directors have driven the Foundation over the years to stay the course.

DD: How have DMRF’s efforts clarified how dystonia affects the brain?

JT: Work by DMRF Scientific Director Emeritus Dr. Mahlon DeLong was groundbreaking and clearly pointed to the brain circuit abnormalities in dystonia. The basal ganglia, structures deep in the brain, have since been a focus of dystonia research for decades now. Scores of DMRF-funded investigators have collectively helped further clarify the underlying neurology of the dystonia brain. What is emerging is a very complex picture of dystonia as a disorder involving brain pathways where interactions among specific neurons impact movement. Central to these problems are neurotransmitters, chemicals that direct body movement. These neurotransmitters are produced and influenced by processes at the microscopic cell level.

DD: How did the DYT1/TOR1A gene discovery mark an important new era in dystonia research? Why are genetic studies important?

JT: One of the major goals of modern medicine is to identify molecular causes of diseases. Genes are the windows into these molecular causes. Once gained, this knowledge helps in designing therapeutic strategies based on biological mechanisms. This is in contrast to current therapies, which suppress symptoms without correcting the underlying problem. Identifying the DYT1/TOR1A mutation as the cause of early onset isolated dystonia played such a role. It showed that this form of dystonia is firmly linked to a gene defect and cellular consequences of it.

This discovery opened a new chapter in dystonia research and prompted more, ultimately also successful, studies in dystonia genetics. DMRF-funded investigators have since identified numerous genes including DYT6/THAP1, DYT25/GNAL, DYT16/PRKRA, and others.

DD: Many investigations funded by DMRF have applied cutting edge techniques or technologies to learn about dystonia, often at critical times. how does the evolution of technology impact dystonia research progress?

JT: Technology drives medical and scientific progress. New tools extend our capability to explore biological mechanisms of disease. Undoubtedly, numerous new technologies, often enhanced by novel computational methods, tremendously help in basic and clinical dystonia research. Especially, modern engineering and material science dramatically improve medical diagnosis and treatment that is available to neurosurgeons and neurologists in the treatment of dystonia. Neuroimaging and deep brain stimulation come to mind as examples—the technologies are rapidly changing.

DD: What are we learning now that investigators are finding commonalities among different dystonia-causing genes?

JT: Clinically speaking, we have multiple forms of dystonia with different causes and different symptoms, yet, we categorize them together as ‘dystonias’ because they all originate in the brain affect movement control in a very specific way. Even though we discover more and more causative genes for various dystonias, we believe that some basic mechanisms, from molecular and cellular to those involving brain structures and networks, are responsible for dystonia in general.

We believe that understanding one form of a well-defined dystonia will help us understand other forms because of their ultimate functional overlap.

DD: Because science can be unpredictable, how important is it for DMRF research efforts to leave room to respond to new or unexpected opportunities?

JT: It is impossible to predict the future of dystonia research in the long run. We know that we have to continue what we started and push for more where knowledge gaps are evident. However, there is always something unknown or unpredictable that might be discovered serendipitously. There might be someone, somewhere, thinking differently, having an original, revolutionary idea or making an unexpected breakthrough observation. DMRF has always been ready for this, making quick assessments and seizing such opportunities because they may disappear and never come back. Our programs are deliberately open and customized to support bold ideas and unconventional, risky projects. Although always measured, these efforts are aimed at one goal: full understanding of dystonia to better treat, and possibly cure, all who suffer from it.

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The Dystonia Medical Research Foundation is a 501(c)(3) non-profit organization dedicated to advancing research for improved dystonia treatments and ultimately a cure, promoting awareness, and supporting the well-being of affected individuals and families.