Conference Coverage

Conference News Update—Federation of American Societies for Experimental Biology


 

References

Antioxidant Therapy May Have Promising Potential in Concussion Treatment
A study conducted by investigators at West Virginia University suggests that antioxidants may play a key role in reducing the long-term effects of concussions and could potentially offer a unique new approach for treatment.

It is estimated that 3.4 million concussions occur each year in the United States, and concussions are common among athletes and soldiers. The development of a readily available oral supplement would have the potential to improve brain function in a percentage of individuals with concussion.

The study adds to recent findings that concussions can lead to chronic traumatic encephalopathy. Head injuries often result in chronic traumatic encephalopathy, a disease associated with long-term brain damage and behavioral symptoms including memory loss, impulsive behavior, depression, and aggression. The number of retired athletes and veterans diagnosed with chronic traumatic encephalopathy has climbed in recent years.

“Concussions can contribute to long-term changes within the brain, and these changes are the result of cell death, which may be caused by oxidative stress,” said Brandon Lucke-Wold, an MD and PhD student at West Virginia University’s Medical School in Morgantown. “This study shows that antioxidants such as lipoic acid can reduce the long-term deficits when given after a concussion.”

In Mr. Lucke-Wold’s research, rats were separated into three groups: a nonconcussed control group, a group that experienced concussive injury, and another concussed group that received lipoic acid supplementation. Seven days after the concussion, the rats were tested for seemingly impulsive behavior through an elevated maze. The rats exposed to concussion without lipoic acid had increased impulsive behavior and spent more time exploring open spaces, which indicates risk-taking behavior.

“This increase in impulsive behavior was an indication of underlying brain damage,” said Mr. Lucke-Wold. Analysis of the brains of the group receiving supplementation showed markedly decreased impulsive behavior. “These findings make sense because lipoic acid works to help reduce toxic free radicals that can damage cells.

“By understanding the mechanisms behind brain injury following concussion, we can more effectively target treatment interventions to reduce these damaging effects,” Mr. Lucke-Wold concluded.

New Compounds Could Offer Therapy for Various Diseases
Newly developed compounds safely prevented harmful protein aggregation in preliminary tests using animals, according to an international team of more than 18 research groups. The research findings suggest that a new class of drugs may be on the horizon for the more than 30 diseases and conditions that involve protein aggregation, including spinal cord injury, Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, diabetes, and cancer.

“Diseases caused by protein aggregation affect millions of people around the world,” said Gal Bitan, PhD, Associate Professor of Neurology at the David Geffen School of Medicine at the University of California, Los Angeles. “We hope that the new compounds will provide therapy for diseases caused by protein aggregation, many of which have no treatment at all.”

The researchers call the compounds that they developed molecular tweezers because of the way they wrap around the lysine amino acid chains that make up most proteins. The compounds are unique in their ability to attack only aggregated proteins, leaving healthy proteins alone.

To develop a new drug, researchers typically screen large libraries of compounds to find ones that affect a protein involved in a disease. Dr. Bitan’s team used a fundamentally different approach to develop the molecular tweezers.

“We looked at the molecular and atomic interactions of proteins to understand what leads to their abnormal clumping,” Dr. Bitan said. “Then we developed a tailored solution. So, unlike many other drugs, we understand how and why our drug works.”

The team is in the process of testing multiple versions of the tweezers, each with a slightly different molecular makeup. For CLR01, one of the most promising versions, the researchers have demonstrated therapeutic benefits in two rodent models of Alzheimer’s disease, two fish and one mouse model of Parkinson’s disease, a fish model of spinal cord injury, and a mouse model of familial amyloidotic polyneuropathy, a rare disease in which protein aggregation affects the nervous system, heart, and kidneys.

“Our data suggest that CLR01 or a derivative thereof may become a drug for a number of diseases that involve protein aggregation,” Dr. Bitan said. “We also found a high safety window for CLR01.”

In one of the safety tests, mice receiving a daily dose of CLR01 that was 250 times higher than the therapeutic dose for one month showed no behavioral or physiologic signs of distress or damage. In fact, blood cholesterol in the mice decreased by 40%, a possible positive side effect of CLR01.

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