The Scoop: Tracking MicroRNAs to Study Brain Dysfunction

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July 1, 2018 (Vol. 38, No. 13)

John Sterling Editor in Chief Genetic Engineering & Biotechnology News

Quadrant Biosciences Believes Human Saliva Holds Key to Better Neuro Disorder Therapies

Richard Uhlig was a retired Wall Street executive when his life changed six years ago.

“My youngest son, a youth hockey player, suffered a significant concussion during a game. It occurred at roughly the same time that NHL hockey star Sydney Crosby was misdiagnosed with a neck injury in addition to a concussion,” says Uhlig. “Watching the way doctors tried to diagnose my son struck me as guesswork and archaic. So I decided to do something about it.”

In 2015, he founded Syracuse, NY-based Motion Intelligence (now known as Quadrant Biosciences) to develop better functional assessment tools and epigenetic biomarkers to diagnose and monitor brain diseases and injuries, including concussion, autism spectrum disorder (ASD), early-stage dementia, Parkinson’s disease, and attention deficit hyperactivity disorder (ADHD).

“We’ve built a world-class bioinformatics platform,” Uhlig tells GEN. “We’ve got thousands of patients and healthy controls all deeply phenotyped. We have access to rich epigenetic and genetic data. We use artificial intelligence and machine learning to look for signatures for different disease states.”

Quadrant Biosciences recently partnered with ChoiceOne/MedSpring to offer the ClearEdge Brain Health Toolkit at select ChoiceOne/MedSpring centers in the Baltimore and Dallas-Fort Worth areas. ClearEdge, developed in cooperation with researchers and clinicians at State University New York (SUNY) Upstate Medical University, is a collection of functional assessments designed to monitor and track subtle changes in cognitive function, balance, and patient symptoms over time.


Brain Health

ChoiceOne/MedSpring will offer ClearEdge assessments for patients who wish to establish baseline measures of their brain health, or who have just experienced a head injury, according to Uhlig, who adds that the initial ClearEdge assessment will be useful as a comparative point to both track patients’ brain health over time and, in the event of an injury such as a concussion, also help assess recovery.

In March, the Hall of Fame (HOF) Players Foundation, established by the Pro Football Hall of Fame, and Quadrant Biosciences agreed to monitor the brain health of retired NFL athletes, using the company’s assessment tools. HOF Players Foundation is a Georgia-based nonprofit organization dedicated to assisting legendary NFL players who are now facing personal difficulties and health challenges.

In addition to participating in the ClearEdge testing, Quadrant Biosciences is collecting saliva samples as part of its research into epigenetic biomarkers for brain health disorders.

Last November, in a paper published in JAMA titled, “Association of Salivary MicroRNA Changes with Prolonged Concussion Symptoms,” researchers from Penn State Medical Center described microRNAs as potential biomarkers for predicting the duration and nature of concussion symptoms in children. Quadrant Biosciences funded part of the research with the goal of bringing a saliva test to market later this year or next.

Human spit may hold the key to better understanding concussions in sports.

Researchers are trying to figure out if a football player’s saliva can tell team doctors something about his brain.

Following a concussion, injured brains release micro-RNAs, which can appear in blood and saliva. When compared to baseline results collected from healthy athletes, the data collected from human spit may be able to tell doctors if an athlete has suffered a concussion or not.

“This will have a profound effect on the way clinicians approach concussion management and treatment, and positively change the trajectory of recovery for so many kids,” Uhlig says. “We fully expect that this line of inquiry will lead to similar applications in adults.”

In April, Quadrant Biosciences signed three licensing agreements with SUNY Upstate Medical University and Penn State University for the global commercialization of epigenetic biomarkers for ASD, Parkinson’s disease, and concussion.


Novel Approach

According to Frank Middleton, Ph.D., an associate professor at SUNY Upstate Medical University and one of the researchers behind the licensed biomarkers, “There have been many attempts to develop biologic tests to help diagnose neurological or neurodevelopmental disorders, primarily using genetic and blood-based assays. Our epigenetic approach, which looks at RNAs in saliva, is highly novel and provides a more robust method of distinguishing affected from unaffected subjects.”

“This epigenetic platform provides an opportunity for clinicians to quickly and objectively assess medical conditions that have historically relied on expert medical opinions. This represents an important step in the development of clinical tools that will revolutionize the way we diagnose and treat our patients,” adds Steve Hicks, M.D., Ph.D., a pediatrician at the Penn State College of Medicine and the site’s lead investigator. “These biomarkers will significantly change the way clinicians treat patients.”

Being able to use saliva and accurately measure these microRNAs is an effective way of looking at injury or disease states, stresses Uhlig. “That’s what we’re using as differentiators for diagnosing not only concussion but also Parkinson’s, ASD, and ADHD, for example,” he continues.

These are products the company is currently researching, and it expects to have the saliva microRNA test for ASD on the market later this year, according to Uhlig.

In characterizing his company, Uhlig explains that it is at the intersection of three trends for which the company positioned itself.

The first is the democratization of big data. “Everything we’ve built has been done in the cloud in Amazon Web Services. So we’ve got the ability to have computer capacity as big as anyone in the world.”

The second trend revolves around the incredible advances in artificial intelligence and machine learning, and the third is the rapidly declining cost in genetic sequencing.

“The combination of these three factors forms the core of our company,” says Uhlig





























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