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From Heredity to Remedy
UND and the Lieber Institute for Brain Development partner to expand the world’s
largest brain repository for the study of brain disorders affecting the genomes
unique to North Dakota
Decades ago, more than a few physicians were convinced their African American patients were less compliant, relative to their Caucasian counterparts, with taking the medications they had been prescribed. Analyses of blood draws from patients of all backgrounds consistently showed that the level of medication present in patients’ bodies was typically lower in African Americans than other groups; researchers simply assumed that this patient cohort was less diligent in keeping up their drug regimen and, by extension, their overall health.
Shaking his head at this idea today, Thomas M. Hyde, MD, PhD, recalls with frustration how such predispositions made their way into several peer-reviewed studies of medication compliance in persons of different backgrounds.
“But as it turns out, these folks weren’t less compliant—they had a much higher incidence of a particular variant of one of the enzymes that degrades this or that drug,” explains Hyde. “They had lower levels of the drug in their system because they metabolized it faster for genetic reasons.”
Indeed, says Hyde, sometimes societal presumptions “serve us poorly when we’re trying to understand the success or failure of treatments among different ethnicities.”
Studying genetic differences in the brain
As Chief Medical Officer of the Lieber Institute for Brain Development (LIBD), a not-for-profit institution affiliated with the Johns Hopkins University in Baltimore, Hyde (foreground right) sees it as his mission to combat such prejudices with science. This is part of the reason why LIBD began collecting brain tissue samples in 2011 with the intent of studying how genetic differences between populations affect the development and treatment of mental illness.
Beginning with a focus on schizophrenia, and expanding to conditions like depression and PTSD, for the past seven years LIBD has dedicated itself to finding new targets for the treatment of complex behavioral disorders, which are often connected to genetics in one or more ways.
But because Hyde can’t fight the good fight alone, he has been tireless in working to develop partnerships with research institutions across the country that also focus on such conditions.
One such institution is the University of North Dakota School of Medicine and Health Sciences (SMHS).
Late last year LIBD, which manages the largest Human Brain Repository in the world, and the UND SMHS announced a partnership—the fourth of its kind—to enlarge the repository, allowing researchers to accelerate the rate and volume of brain tissue collection.
“We’re thrilled to embark on this partnership with the LIBD, which will give persons from North Dakota and the upper-Midwest a chance to participate in the exciting research of brain development and function already ongoing elsewhere in the country,” noted Mary Ann Sens, MD, PhD, professor and chair of the SMHS Department of Pathology, who is spearheading the tissue collection effort at UND. “Many local families are concerned with a wide variety of mental disorders in loved ones and within this community, including things like post-traumatic stress disorder and depression. By collaborating directly with world leaders in neuroscience through the Lieber Institute, we can expand greatly our clinical translational research programs and bring a new level of excellence and opportunity to the region.”
This new collaboration will increase the diversity of brain samples collected nationally, says Dr. Sens (right), offering researchers the opportunity to expand the study of neurological and cognitive disorders across the unique genomes that make up the population in North Dakota and the surrounding region.
“We were attracted to North Dakota because you have a large Scandinavian population and a large Native American population, both of which have dealt with a lot of things like addiction and depression,” Hyde told North Dakota Medicine in a sit-down interview at the School. “And you have a large veteran and active-duty military population in North Dakota. We’re heavily invested in PTSD research as well, so we’re in desperate need of tissues to help us understand the biology of this illness. We’re already working with the Department of Defense and the VA to develop new drug targets for the more effective treatment of this disorder.”
So how does the tissue acquisition process work? According to Hyde, establishing a relationship with a regional Medical Examiner (ME) is a vital first step.
“When someone arrives at the ME’s office for an autopsy, if the deceased person’s brain is in good condition and fits one of our diagnostic criteria—he or she was either a relatively healthy individual or someone with a major psychiatric disease or addiction—we contact next of kin. We talk to them about the donation process and get their informed consent.”
If consent is confirmed, LIBD works with the partner institution and county Medical Examiner—Dr. Sens in UND’s case—to perform an autopsy on the deceased person, gathering brain biopsy material for preservation and study.
“We are on the leading edge of applying advanced population genetics to human brain tissue for the advancement of medical science,” concluded Hyde, who hopes LIBD might further partner with the SMHS to provide graduate and medical students opportunities to conduct research at the LIBD facility in Baltimore. “Together, researchers across the country are utilizing this tremendous network of institutions to discover novel drug treatments and prevention strategies for neurological disease for persons of different backgrounds.”
Since opening in 2011, the LIBD has acquired over 2,200 brain samples for conducting research critical to understanding brain pathology. With collection sites in Maryland, Michigan, and California, the repository continues to grow at a rate upwards of 500 new cases per year.
“Our values of service and respect for families are paramount with this collaboration, which assures that our state is represented in vital neuroscience research into the complex areas of mental health, post-traumatic stress, autism, and a host of other complex diseases,” Dr. Sens concluded. “We’re honored to participate.”