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Clearing the 'fog'

Many of the side effects from chemotherapy are well documented: Fatigue, nausea and hair and weight loss. But there is another one that has split the medical community about whether is even exists. It's called chemotherapy-induced cognitive deficits or "chemo fog" and pharmacologist Ellen Walker hopes her research not only proves its real, but finds the cause.

Walker, a PhD and associate professor of pharmacodynamics at the School of Pharmacy, received a $1.5 million dollar National Institutes of Health grant at the beginning of this year to study the possible effects of drugs used during chemotherapy on cognitive impairment. It's a big grant, with perhaps even bigger implications for how researchers and patients deal with chemotherapy-induced cognitive deficits, which chemotherapy patients liken to being in a fog, as if they're brain isn't working right. Misplaced items, inability to multi-task, short-term memory loss are hallmarks of the condition. And while there is clinical evidence to support its existence, research studies on the topic are scant.

"My colleague Bob Raffa and I were stunned at the lack of published literature, considering cancer patients have been getting chemotherapy for nearly 50 years," said Walker. "Most studies have looked at how well chemotherapeutic agents kill the tumor, not if they cause a cognitive deficiency, like memory loss."

Walker and Raffa decided to fill that void. Two years ago, Walker and PharmD student John Foley, set out to see if certain chemotherapeutic agents caused memory and learning deficits in mice. They tested two older drugs commonly used to treat breast cancer, a cancer with recently higher survival rates whose survivors have dominated the limited clinical research on chemotherapy-induced cognitive deficits. They suspected the drugs, methotrexate and 5-fluorouracil, weren't toxic alone, but when given together, could cause deficits. Six months into their research, their hunch proved right.

"Alone, methotrexate didn't cause learning or recall deficits in mice when given once. Mice given 5-flurouracil once showed some deficits in recall, but when we gave the mice both drugs, it had a synergistically worse effect on their ability to learn and remember."

In other words, the mice forgot what they learned a day after being given the chemotherapeutic agents. And as Walker expanded their research, giving the drugs once a week for three weeks, they saw even more deficits than just giving it acutely. Armed with their results, this one-time side project became a priority. What followed were months of research and the involvement of more colleagues to help define better dose combinations and regimens. But there was also the ping-pong of NIH reviews and revisions to endure and Walker and her research team had run out of money. In March, 2008, a $50,000 bridge grant through the Office of Research and Strategic Initiatives allowed her research to continue.

Eight months later, the NIH sent word that they were not only funding Walker's research with a five year, $1.5 million dollar grant, but she received a priority percentile ranking of 0.8, placing it at or very near the top of all peer applications.

"I had to look at the score twice because I couldn't believe it," said Walker.

It wasn't just Walker who was impressed by the score.

"I was delighted to learn about the grant and its truly outstanding ranking," said Larry F. Lemanski, Ph.D., Senior Vice President for Research and Strategic Initiatives at Temple. "This major grant from the National Institutes of Health will allow Dr. Walker to significantly expand her research programs. At the same time, the award will increase Temple's reputation as a major player in this very important field of biomedical research."

Indeed the funding will allow Walker to triple her efforts. She can put someone full-time on the project and study four more chemotherapeutic agents. And down the road, she would like to figure out how to protect the brain before chemotherapy to prevent chemo fog.

For now, there is still controversy surrounding chemo fog, as clinicians and scientists debate if the disease itself or the drugs to fight cancer cause it. Other culprits could include genetics, hormone inhibitors, anemia and early-onset menopause. Instead of a natural onset, chemotherapy often catapults women into menopause, potentially leaving them fuzzy-minded. And there are those who doubt chemo fog is real. Walker believes it is. She recalls how during her mother's battle with breast cancer, she put a chicken still covered in plastic wrapping in the oven for dinner.

"It seemed like she wasn't always thinking clearly even after her chemotherapy was over. I always wondered was it the psychological stress of cancer, the chemotherapy, or some other side effect of the many medications she received."

Ellen Walker may well be on her way to finding the answer.


Contact: Megan Chiplock
Temple University

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