David Auerbach, PhD, is applying a unique approach to study how genetic diseases impact multiple systems in the body. This has led his lab to study multiple rare diseases, with the hope that results from their studies will lead to discoveries that can be applied to more common conditions.

“People might say ‘Only one in 2000 people have this disease, why are we going to invest this time and effort into studying this rare disease?’’ says Auerbach. “The thing is these rare diseases provide a great model and tool to understand what are the substrates and triggers for these events.”

Now, his lab is at the forefront of investigating how rare genetic epilepsies—like Dravet Syndrome, Lennox-Gastaut Syndrome—impact multiple organs, particularly the heart. Their research aims to uncover why patients with these conditions face a high risk of sudden unexpected death in epilepsy (SUDEP), a devastating and poorly understood consequence of severe epilepsy.

It takes a lot of work to study rare diseases. Justin Ryan, PhD, brings his background as an applied mathematician to the Auerbach lab, compiling and analyzing data.

“Dravet syndrome is extremely rare which poses a huge problem when trying to build large datasets for research studies” says Ryan. One in 20,000-40,000 people have Dravet Syndrome. “Over six years Dr. Auerbach has acquired data from multiple institutions across multiple countries and even continents.”

PhD candidate Veronica Singh has been exploring the heart-brain genetic connection from the other direction. Long QT Syndrome (LQTS) is typically thought of as a heart abnormality; a genetic mutation causes electrical disturbances in the heart, which can lead to lethal arrhythmias. Only 0.05% of the population have LQTS.

“The same genetic variant that alters ion channel function in the heart, is also expressed in the brain,” Singh explains. “If it’s causing electrical abnormalities in the heart, it's probably doing that in the brain.”

Singh recently published a study that investigates the heart-brain connection in LQTS; they developed an animal model that closely reproduces the brain and heart conditions seen in people with LQTS.

“We study this disease at the molecular, cellular, whole animal, and clinical levels,” Singh says. The goal of this multi-level approach is to better understand the underlying causes for the disease, and ultimately to identify treatments.

"Dr. Auerbach showed a few years ago that people with LQTS not only experience cardiac arrhythmias, but also seizures. Additionally, other groups have shown that genetic variants that cause LQTS are detected when doing genetic analysis of SUDEP cases,” explains Singh.

“SUDEP is a horrible, tragic event,” Auerbach adds. "It’s very similar to Sudden Infant Death Syndrome (SIDS); we don't understand the cause of it. If we can identify some genetic variants that we know lead to, for example, cardiac abnormalities, we can develop therapies.”

While challenging, all agree that it’s rewarding and worthwhile to work towards understanding these rare genetic diseases.

“Building on my background in mathematics, I joined this research team to apply my skills in a new way to better investigate biomedical questions. The biology and biomedical aspects really speak to me,” explains Ryan.

“We’ve been able to travel to conferences where we can meet with people who have lost someone due to SUDEP or cardiac death, and clinicians that are treating people with these rare diseases,” says Singh. “It's easy to read about these things at your desk in the lab, but it is very powerful to see what kind of an impact you can have and how our research studies may have a future impact on the lives of people with rare diseases. That's probably what really sealed the deal for me to join the lab.”

You can read more about the Auerbach Lab’s work on genetic diseases here-

https://www.upstate.edu/pharm/research/labs/auerbach/index.php

For more on Rare Disease Day, visit rarediseaseday.org

Caption: Members of Dr David Auerbach's lab are, from left, Justin M Ryan, PhD, Veronica Singh, Laura Wengert, David Auerbach, PhD, Kyle Wagner and Laura Williams.

 

Upstate is holding a rare disease lunch and learn panel Feb. 28, to mark Rare Diseases Day at noon in 9295 Weiskotten Hall. Panelists are from Upstate Frank Middleton, PhD; Joan Pellegrino, MD; Violeta Yu, Dewpoint Therapeutics; Sharon Forbes, Central New York for Parents Project Muscular Dystrophy (PPMD); Alison Dwyer Hoke, MD, president of Two Smiles One Hope Foundation, Inc.; and Thomas W Parry Jr, rare disease patient and advocate. The event is hosted by Upstate Student Government and the GENEius Club. R.S.V.P. here: https://campuslife.upstate.edu/event/10993429. Questions? Email [email protected].