Spit It Out! How saliva may provide the key to sports-related concussion

concussionSRxA’s Word on Health has reported several times on the problems of concussion among football players and cheerleaders. So we couldn’t help but sit up and take notice of an article in our local newspaper about some cutting edge research taking place yards from our front door.

The third floor of Bull Run Hall on George Mason University’s Prince William campus plays host to plenty of mind-bending science projects – laser capture microdissection, protein electronics and high-resolution mass spectrometry to name but a few.

Yet the most complex and potentially influential findings to emerge from the school’s College of Science might come down to a kid spitting in a cup after football practice.

Once a week athletic trainers collect saliva samples from the 12- and 13-year-old kids playing for the Jets, an A-League football team in the Central Loudoun Youth Football League. Then they send them to Dr. Shane Caswell, a George Mason professor and pioneer of the world’s first salivary biobank designed for concussion research in athletes.

Caswell stores the saliva in a freezer he dubs the “spit repository.” He eventually extracts the samples and runs them through sophisticated machinery to determine changes in protein variance. By comparing each kid’s spit samples to previous submissions, he hopes to uncover a handful of proteins that can detect concussions.

George Mason scientistsWorking alongside Caswell is Dr. Chip Petricoin. Long accustomed to studying protein biomarkers for cancer research, Petricoin never imagined he’d wind up plying his trade for studies on traumatic brain injury and concussions.  But the seed was planted six years ago, when he was called up to Fort Detrick to conduct a site review for a company that had been given a grant from the army to do concussion research. Petricoin admired their efforts, but he realized that his own work with cancer biomarkers could reap significant benefits for the concussion research that remained in its nascent stages.

A year later he found himself working in the same building as Caswell, whose extensive background in athletic training was getting him increasingly involved with concussion research. The two discussed their respective endeavors and quickly realized they could join forces.

The university’s College of Science and College of Education and Human Development began funding their efforts last year. Since then, Caswell and Petricoin have begun to explore the vast quantities of information stored in athletes’ salivary biomarkers.

Think about the biomarker content of a sample like an iceberg,” said Petricoin, co-director of the university’s Center for Applied Proteomics and Molecular Medicine. “The concept of what you see is only the tip of the iceberg? That’s kind of like biomarker research. Things that have been seen before are just the tip of what really is there. If we could go all the way down and see everything, you’d see a whole new iceberg. So we’re kind of going a mile deep now in the iceberg biomarker research.”

athlete spittingIndeed, the depth of these largely uncharted waters became apparent when the duo began their work with the Jets this fall using eight saliva samples. A few weeks after collecting those baseline samples, they used the nanotechnology at their disposal to examine new samples from four of the same kids who had recently suffered concussions. After compiling a list of proteins, they found that 60% of their list featured proteins that had never been described.

The process generates an information archive that’s larger than anyone’s ever seen before in saliva,” Petricoin said.

Caswell and Petricoin are currently working on 37 concussion cases, a total that increases every week with new samples arriving from different sources. They’re collaborating with Prince William County Public Schools, as well as intercollegiate athletics at Marymount University and George Mason.

The Jets’ head coach, Rob Scola, says his team has so far adapted nicely to the study. George Mason sends a certified athletic trainer to the field to provide care and to collect data on hits the players endure. The trainer tapes every game and practice, something that allows coaches to see what they’re doing right and wrong in their efforts to teach proper heads-up tackling techniques. Players also wear helmets with sensors that detect the force and location of impacts sustained in practices and games.

It’s all part of an effort to determine what measures coaches should take to minimize players’ risk of head trauma on the football field, where the rate of brain injuries is higher than in any other youth sport.

It’s very hard to get information from a very small team in a very small league and then extrapolate that,” Scola said. “I think that as Mason starts to expand the study, I think there will be some really interesting pieces of information that come from that, which I believe can be helpful to the league and football as a whole. I think it’s a phenomenal first step.”

Part of the project’s appeal lies in its lack of hassle. Biomarker work has traditionally come from blood and spinal fluid samples, which are rooted in far more invasive processes than simply spitting in a cup.

If I were to go out on the field and say, ‘Hold on a second. I want to take your child’s blood or their cerebral spinal fluid.’ That’s game over. We can’t move forward,” Caswell said. “This is a non-invasive tool that is rapidly deployable. There’s no threat of infection, it’s easily done and it provides a great deal of information.”

Caswell and Petricoin’s work with the Jets has opened the door to broader studies that extend to the entire lifespan of an athlete’s career. The hope is that parents will have their children give samples when they begin participating in youth football, ice hockey, soccer, or whatever sport they choose to play. They can then follow that up by giving more samples as they pursue the sport in high school, college and beyond.

“You are then able to track at various time points throughout someone’s career and identify how their marker is changing and then maybe one day compare it to a database that could help inform decisions about whether or not that individual should retire from play, whether that individual is suffering any adverse consequences from their participation,” Caswell said.

blue mouthgardEven more ambitious is their ultimate goal of implementing the biomarkers into a clinical diagnostic device. Petricoin envisions a mouthguard that turns from clear to blue when a concussion is detected. The technology, he says, is there – impregnating the nanoparticles into the mouth guard, binding the biomarkers and producing a color shift are concepts that have already been engineered.

The hard part is nailing down the biomarkers. For the moment, all Caswell and Petricoin are trying to do is identify what’s in the saliva. As the data mounts, they hope to reveal protein distribution patterns that coincide with repeated head trauma.

Caswell, a former hockey player who once returned to the ice minutes after suffering a concussion only to realize minutes later that he wasn’t carrying his stick, believes those patterns will come and that his team is well-positioned to make meaningful discoveries that could impact concussion policies on a greater scale.

If and when they do, we’ll be sure to let you know.

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Truth Test for Knees?

Orthopedic surgeons have identified a molecular biomarker that could potentially help people with knee injuries save time, and money and the risks of surgery.

According to a study just published in The Journal of Bone and Joint Surgery researchers from California, Florida, Pennsylvania and New York have identified a biomarker found exclusively in patients with  torn cartilage.  Potentially, this simple test could help patients avoid the time and cost of undergoing an MRI and identify those who are candidates for surgery rather than those who have less operable conditions.

By analyzing the synovial fluid surrounding the knee joints of 30 patients with meniscal tears, researchers found a protein complex called fibronectin-aggrecan that wasn’t present in 10 volunteers with normal, pain-free knees.  To date, fibronectin-aggrecan has not been found in patients with osteoarthritis.

An estimated 700,000 arthroscopic knee operations are performed each year in the U.S. based on the results of MRI scans, which can cost in the region of $2,500.

While surgeons can use MRIs to try to discern the root of a patient’s knee pain, MRIs often cannot differentiate between inflammations from natural degeneration and a full-fledged tear.

Traumatic and degenerative injuries look the same on MRI,” said Gaetano Scuderi, Professor of  orthopaedic surgery at Stanford School of Medicine. “In a 50-year-old, we can’t tell the difference.”

However, correctly identifying a cartilage tear is only one obstacle. Sometimes, patients sustain pain  after corrective surgery because the tear is not actually the root of pain.

Sometimes you would think you did a great job but the patient still had pain,” Scuderi said. “Why did this  person not get better when another person did?”

Previous studies have shown that surgery is only effective for a torn meniscus or cartilage. Knee pain caused by age-related osteoarthritis or injured hip ligaments can resemble a torn meniscus but isn’t helped by surgery. This distinction isn’t always clear on MRI scans.

In a clinical setting, this new biomarker could effectively differentiate knees with pain-inducing cartilage tears that are responsive to surgery from knees with only natural cartilage degradation.

This would be especially beneficial to older patient populations in whom MRIs always show degeneration. The biomarker test offers a cheaper and more specific identification of pathology. Better still, the researchers are hoping to image the molecule non-invasively as opposed to aspirating it for assay.

Differentiating Chronic Fatigue Syndrome and Lyme Disease

Both chronic fatigue syndrome (CFS) and Lyme disease can result in profound exhaustion that may be prolonged and debilitating. It can be accompanied by either excessive sleeping or insomnia. Yet oftentimes these diseases are dismissed by family, friends and physicians or attributed to simple tiredness from overwork or stress.

For such patients, hope may be in sight.  A new study reveals that researchers have discovered a test that can distinguish patients with Lyme disease from those with chronic fatigue syndrome, and also from people in normal health.

In the study, investigators analyzed spinal fluid from 43 patients with chronic fatigue syndrome, 25 people who had been diagnosed with and treated for Lyme disease, (neurologic post-treatment Lyme disease – nPTLS) and 11 healthy people.

Until now, there have been no known biomarkers to distinguish between Lyme disease and Chronic Fatigue Syndrome , nor strong evidence that the central nervous system was involved in the two conditions.

“Spinal fluid is like a liquid window to the brain,” says Steven E. Schutzer MD, of the University of Medicine and Dentistry of New Jersey.

The researchers identified 738 proteins present only in the spinal fluid of CFS patients and 692 proteins found only in the spinal fluid of nPTLS patients.

One next step will be to find the best biomarkers that will give conclusive diagnostic results,” said Dr. Schutzer. “In addition, if a protein pathway is found to influence either disease, scientists could then develop treatments to target that particular pathway.”

Have you been misdiagnosed, mistreated or accused of malingering?  SRxA’s Word on Health would love to hear from you.

Heightened Scrutiny of Food & Supplement Health Claims

Health claims made by food and nutritional supplement manufacturers should face the same level of regulatory scrutiny as those made by drug and medical device manufacturers, says a new report from the Institute of Medicine (IOM).

Food and nutritional supplement marketers often make health claims based on how individual ingredients in their products affect biomarkers (physiological characteristics that can be measured and evaluated objectively) such as cholesterol or glucose levels or tumor size. Thus, the manufacturer of a breakfast cereal that contains a cholesterol-lowering ingredient, such as fiber, might boast that its cereal has heart health benefits without clinical proof of improved outcomes.

Faced with a proliferation of health claims being made by food and supplement manufacturers, the FDA’s Center for Food Safety and Applied Nutrition asked the IOM in 2008 to recommend a framework for the evaluation of biomarkers.

Commenting on the report, IOM member Harlan Krumholz, MD said, “This is a groundbreaking report that tells us we should really think carefully about the use of biomarkers and surrogates.”

SRxA’s Word on Health is pleased to hear that the food we eat will be given as much attention as the drugs we take, but hopes that the process can be somewhat faster!