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Weinberg Researchers Fight Cancer, Cerebral Palsy, Obesity

Research Roundup

A New Preventative Measure for Cerebral Palsy 

Cerebral palsy is a neurodegenerative condition caused by brain damage before, during, or shortly after birth. It affects 750,000 children and adults in this country. Too much nitric oxide in the brain, caused by hypoxia, or oxygen deprivation, leads to the fetal neurodegeneration. This year, Northwestern University chemists developed two compounds that selectively inhibit a brain cell enzyme responsible for the production of nitric oxide. In pre-clinical trials, Richard B. Silverman, John Evans Professor of Chemistry and Sidhartha Tan, neonatologist from North Shore University Health System, found that 83 percent of animals treated with the compounds prior to hypoxia were born without any symptoms of cerebral palsy. 

Silverman says the next step is applying for NIH funds to collect pharmacokinetic and toxicological data in animals under conditions that are recognized by the FDA as standard in the industry. 

Nanoparticles Boost Arsenic as Cancer-Fighter 

Despite its reputation as a lethal poison, arsenic trioxide has its share of beneficial properties for humans. Clinical trials have demonstrated arsenic’s anticancer agents as a potential primary treatment for acute promyelocytic leukemia. However, the toxicity of arsenic trioxide and its ability to rapidly leak out of the nanoparticles which enclose it has until now hindered its use as a cancer treatment. Thomas O’Halloran, chemistry professor and a scientist at Northwestern’s Center of Cancer Nanotechnology Excellence, appears to have an answer to the problem. By encapsulating arsenic trioxide within a lipid-based nanoparticle coated by polyethylene glycol and folic acid, the arsenic payload can be delivered to the site of the tumor without affecting other types of cells. The composition of the nanoparticles makes them unstable when subjected to the slightly acidic conditions found inside tumor cells, so they disintegrate and release arsenic trioxide only after being taken up by malignant cells. O’Halloran and his team of researchers also found that nanoparticle-encapulated arsenic trioxide is even more potent than the drug by itself. 

For Weight Control, Avoid Late-Night Snacks 

We are beginning to understand why midnight snacks are such a bad idea in a nation battling an obesity epidemic. A new study spearheaded by Fred Turek, director of Northwestern’s Center for Sleep and Circadian Biology, shows for the first time the causal relationship between meal timing and weight gain. “How or why a person gains weight is very complicated, but it clearly is not just calories in and calories out,” says Turek, also professor of neurobiology and physiology, “We think some factors are under circadian control.” Our circadian clock regulates our daily cycles of feeding, activity, and sleep with respect to external dark and light cycles. Recent studies have found the body’s internal clock also controls energy use. 

Researchers in Turek’s lab observed that late-shift workers tended to gain weight and that their jobs forced them to eat at times when they would normally be sleeping. To examine the reasons for this, they divided lab mice into active-period eaters and rest-period eaters. The mice that were fed a high-fat diet during their normal sleeping time increased in weight by 48 percent, while those who ate during their natural waking hours increased by only 20 percent. “Better timing of meals, which would require a change in behavior, could be a critical element in slowing the ever-increasing incidence of obesity,” says Turek. 

Next, the group will study the molecular mechanisms behind their observation that timing of meals can lead to weight gain. 

Detecting Low-Level  Prostate Cancer 

Prostate cancer is second only to lung cancer as the leading cause of cancer death for men in the United States. Now a nanotechnology tool developed by Northwestern University researchers is offering new hope for earlier detection. Led by Chad Mirkin, George B. Rathmann Professor of Chemistry, and William J. Catalone, M.D., professor of urology, the researchers have detected previously undetectable levels of prostate-specific antigen in post-prostatectomy patients using a nanoparticle-based bio-barcode assay 300 times more sensitive than commercially available PSA tests. This means that doctors will be able to diagnose men with prostate cancer recurrence years earlier than is currently possible. Mirkin said, “This level of sensitivity in detecting low concentrations of PSA will take the blinders off the medical community, especially when it comes to tracking residual disease.”