VTC Professor Awarded NIH Grant to Study Potential Cure for DiGeorge Syndrome

The human brain begins to assemble itself shortly after conception as more and more brain cells connect to form circuits throughout the brain.

Genes provide the blueprint for construction, but sometimes the blueprint is incomplete, the connections are not made, and the circuit fails. In some cases, far from being fixed, problems occur long before they are even recognized.

DiGeorge syndrome, also known as 22q11.2 deletion syndrome, is a genetic disorder that affects 1 in 3,000 babies. It begins with the deletion of one of her two copies of a small number of genes on human chromosome 22, and the cascading effects include cardiovascular problems, craniofacial developmental problems, and child malnutrition. Includes Autism Spectrum Disorder and Schizophrenia as we age. By the time these symptoms are recognized, the opportunity for medical intervention is long past.

But now, Anthony-Samuel LaMantia, a professor at VTC’s Fralin Biomedical Research Institute, has identified a key factor in the chain of events. And within that timeline, the narrow window during which help might come.

Lamantia, director of the Institute’s Neurobiology Research Center and faculty member of the Faculty of Science, will take advantage of the window of opportunity with a $3.4 million grant over five years from the Eunice Kennedy Shriver National Institute of Child Health. research the possibilities. Human Development, part of the National Institutes of Health.

LaMantia’s research has the potential to inform new therapeutic strategies that do not currently exist for autism and schizophrenia associated with DiGeorge syndrome. DiGeorge syndrome is one of the few common genetic syndromes that puts people at increased risk of developing autism and schizophrenia. Moreover, understanding the underlying disruption of brain development by DiGeorge syndrome provides an opportunity to identify how these disorders arise due to defective genetic instructions for building the brain. Offers.

LaMantia’s lab, one of the few in the world addressing this question, has been studying DiGeorge syndrome for over 20 years. The lab is digging deep into how the brain’s circuits are constructed to understand exactly what causes the syndrome.

I think 20 years of research has provided a foundation for thinking differently about this disease in the clinic. It is a neurodevelopmental disorder that interferes with a very specific and identifiable stage in brain development. And as we now turn to one of the final stages of brain development, which we believe is most likely able to make adjustments without damaging others. .”

Anthony-Samuel LaMantia, Professor, VTC Furalin Biomedical Institute

LaMantia believes that mitochondria — the powerhouses of cells — are central to disrupting brain development in DiGeorge syndrome.

Typically in the developing brain, mitochondria in neurons in the cerebral cortex create long-distance connections to other parts of the brain, turning circuits on and off to make sure everything is functioning properly. I have enough energy to

In DiGeorge syndrome, the mitochondria are starved of oxygen and lack the energy to make the necessary connections. The reason for this disruption can be traced to several genes in the region of her chromosome 22 that is deleted in DiGeorge syndrome. The imbalance of having only half of these genes, the proteins they encode, and the mitochondrial support they provide, prevents the brain from making enough connections during development, leading to dysfunction. It is the basis of the system of

Although many of the effects of the syndrome occur prenatally, or before the disease is diagnosed, mitochondrial defects that disrupt these final connections are late enough in brain development to allow intervention. will occur.

“If you’re looking to fix it, that’s probably the only viable place to fix it, and it won’t cause other problems in the process.” We are lucky because we can support mitochondria through relatively simple and very safe means, such as nutritional supplements and more precisely targeted drugs.”

LaMantia is also Professor in the Department of Biological Sciences, Virginia Tech School of Science. Her collaborators include her Michael Fox of the Fralin Biomedical Research Institute and Professor and Director of the Virginia Tech Graduate School of Neuroscience. Fralin Biomedical Research Institute Assistant Professor Shannon Farris, Assistant Research Professor Daniel Meechan, Associate Research Professor Greg Crabtree, and Associate Research Professor Thomas Maynard of the Fralin Biomedical Research Institute. Alison Tege, Research Assistant Professor, Department of Statistics, University of Science, and Andrew Ottens, Associate Professor of Anatomy and Neurobiology, Virginia Commonwealth University.