UWM brain research supports drug development from jellyfish protein

With the research support from the University of Wisconsin-Milwaukee, a Wisconsin biotech company has found that a compound from a protein found in jellyfish is neuro-protective and may be effective in treating neurodegenerative diseases.

Testing of aequorin has yielded promising results, said Mark Y. Underwood of Quincy Bioscience located in Madison. Researcher James Moyer, Jr., an assistant professor at UW-Milwaukee, subjected brain cells to the "lab" equivalent of a stroke, and more than half treated with aequorin survived without residual toxicity.

Why does it work? Diseases like Alzheimer's are associated with a loss of "calcium-binding" proteins that protect nerve cells, said Moyer. Calcium is necessary for communication between neurons in the brain, and learning and memory are not possible without it. But too much of it leads to neuron death, interfering with memory and contributing to neurodegenerative diseases.

"There are ways in which cells control the influx of calcium, such as sequestering it by binding it with certain proteins," said Moyer. "If it weren't for these proteins, the high level of calcium would overwhelm the neuron and trigger a cascade of events ultimately leading to cell death."

Calcium-binding proteins decline with age, however, limiting the brain's ability to control or handle the amount of calcium "allowed in."

Aequorin, the jellyfish protein, appears to be a viable substitute.

Moyer, like Underwood, is interested in the "calcium hypothesis of aging and dementia," which is just one of many theories that attempts to explain what is going on in neuron degeneration.

He became interested in aequorin as an undergraduate at UW-Milwaukee, after reading an article that linked the stings of jellyfish with the symptoms of multiple sclerosis, a disease of the central nervous system that his mother has.

Aequorin was discovered in the 1960s and has been used in research for a long time as an indicator of calcium. But the protein has never been tried as a treatment to control calcium levels. Underwood believes his company is at about the 12-year mark in the typical 15-year cycle for a new drug to be developed.

Moyer's research centers on brain changes that occur as a result of aging. Specifically, he is interested in the part of the brain called the hippocampus, which is responsible for forming new memories. These capabilities not only deteriorate in neurodegenerative disorders such as Alzheimer's disease, but they also become impaired simply by aging.

Aging increases the number of "doors" that allow calcium ions to enter the cells, he said.

Moyer, who came to UW-Milwaukee from a post-doctoral position at Yale University, performs Pavlovian trace conditioning experiments to evaluate aging-related learning and memory deficits. These tasks first teach rodents to associate one stimulus with another and then test their memory of the association. During training, the stimuli are separated by a brief period of time, which requires the animal to maintain a memory of the first stimulus. The "stimulus free" period makes the task more difficult, especially for older animals.

Moyer's work also has implications outside of disease. He is able to show that at middle age, when the animal's learning ability or memory is not yet impaired, it already shows a drop in the number of neurons that contain an important calcium-binding protein.

"That cellular changes precede memory deficits indicates there is a window of opportunity for intervention before it's too late," he says. "Once the cells are lost, there is little chance of regaining normal brain function."

Source : University of Wisconsin - Milwaukee