Berge Minassian, MD, is a Professor in the Departments of Pediatrics and Neurology at UT Southwestern Medical Center. Dr. Minassian is a pediatric neurologist whose clinical specialties are epilepsy, neurodegenerative diseases, and neurogenetic conditions. The Chief of Child Neurology at UT Southwestern, he also leads the Neurosciences Center at Children’s Health in Dallas. He serves on the faculty of the Children’s Medical Center Research Institute at UT Southwestern, as well. Dr. Minassian has been active in neurogenetics research for his entire career. Two of his primary interests have been Lafora disease, for which his lab discovered the genes, and APBD. In 2022, Dr. Minassian received a Million Dollar Bike Ride research grant to support the translation of glucan biomarkers that he and his team have found in animal models of APBD into biomarkers for patients with APBD.
We interviewed Dr. Minassian recently to give you a chance to get to know him and the innovative APBD research being done at UTSW Medical Center.
Dr. Minassian and his team
Q. What inspired you to get into research?
Dr. Minassian: A true understanding of disease requires uncovering root causes. That, in a word, is neurogenetics!
Q. Your work focuses on the translation of glucan biomarkers that you and your team have found in animal models of APBD into biomarkers for patients with APBD. Tell us about this.
Dr. Minassian: My lab works on polyglucosan bodies, which are insoluble glycogen molecules that are the hallmark of APBD. We and other researchers have shown that the size of the glycogen chains in APBD is longer than normal glycogen. Glycogen, which can be thought of as a long chain of sugars, is broken down into smaller chain links. Using mass spectroscopy, we were able to detect the distribution of the chain links from the breakdown of glycogen. We found that this distribution was abnormal in urine from mice that resemble APBD. We are now collecting urine from patients with APBD to see if we can find the same difference in patients that we see in the mice.
Q. How is this work progressing?
Dr. Minassian: So far, we have characterized the biomarker in the mice and characterized its response after treating the mice with gene therapy. We had to make changes to how we look at the biomarkers due to the biochemical differences in the mouse and human urine. We are now getting ready to receive urine from patients from across the USA and to see if we can differentiate the biomarkers in these patients from family members or caretakers and if these biomarkers are worsened in patients with a higher disease burden.
Q. Have there been challenges?
Dr. Minassian: Because the patients with APBD are so rare and spread out across the USA and the world, no one center has a lot of patients who can easily collect samples to perform studies. We are working on establishing a way to get samples from around the country and figure out how to make sure the lab tests are accurate with different conditions.
Q. What has surprised you about the discoveries from your lab and their impact?
Dr. Minassian: Because what we don’t know is so much vaster than what we do, often our hypotheses do not prove correct. Notwithstanding, the results of experiments raise new questions, afford new insights, and guide us step by step to uncovering the hidden mysteries of biology and the brain!
Q. Your research has implications for clinical trials for APBD. Tell us about this.
Dr. Minassian: Due to the large cost associated with running a clinical trial, most clinical trials are done on a time frame of 6 months to two years. This is really a tremendous bar in the case of APBD because of its protracted disease course. A drug would have to show a change in a functional outcome in just 2 years.
The medical community and the FDA understand this challenge and so there exists alternative approval processes for drugs that are based off of biomarkers. In simple terms, if you can show that a biologically sound biomarker can prognosticate disease severity or outcome, and you have a reasonable expectation that this would be improve with treatment, you may be able to tool for signals of treatment response in a short amount of time. There are a lot of things that happen before and after, but that’s the gist. This mechanism was recently used to gain approval for a drug called Tofersen for ALS. If we can validate our biomarker in patients with APBD, we can incentivize companies to do a clinical trial based on the biomarker.
Thank you, Dr. Minassian. We wish you much success on behalf of our community!
