Oct 4, 2013

New Results In Alzheimer Reported At Alzheimer's Association International Conference

"Even negative trials provide critical information to the research community for application in future studies to help us find better treatments, which are so desperately needed,” said Maria Carrillo, Ph.D., Alzheimer's Association vice president of Medical and Scientific Relations

In May 2013, the Gammaglobulin Alzheimer's Partnership (GAP) study researchers reported that the results were negative on the main outcome measures, two well-established tests of cognition and daily functioning. At the same time, they reported favorable cognitive changes in two pre-specified subgroups. According to the data presentation, the study was not powered to show statistical significance in the subgroups.

For Norman Relkin, lead investigator of the GAP study, the results do not provide grounds for prescribing IVIG in Alzheimer's disease but, although primary clinical outcomes are unequivocally negative, there are signals in the clinical and biological markers in some subgroups: "With the understanding that we cannot draw conclusions about IGIV's effectiveness in these subgroups from these results alone, results support that IVIG can target beta amyloid and that the antibodies it contains can reach the brains of people with Alzheimer's when administered through the bloodstream."

The successes of IVIG in animal models of Alzheimer's and early stage trials in people make researchers continue to pursue how IVIG may work in the brain, despite the negative results of the Phase 3 IVIG trial.

Three month old mice were treated intravenously with either IVIG or saline and their brains were examined. They found that the IVIG-treated mice experienced a small but statistically significant decrease of tangle pathology in brain cells of the hippocampus, a brain area that controls memory, compared to saline-treated mice. They found also that IVIG treatment resulted in a 40 to 50% increase in plasma levels of several genes that are involved in maintaining proper neuronal function.

IVIG may make neurons less vulnerable to damage from reactive oxygen species

Lahiri and colleagues recently showed that treatment of degenerating rat brain cells with IVIG protected the structure of the cells and enabled them to survive longer. They hypothesized that IVIG treatment might also preserve and protect human brain cells. They created primary human fetal brain neuron (HFN) cultures and treated them with several different doses of IVIG. The cell cultures were then exposed to reactive oxygen species (ROS), molecules that have important roles in communication between cells and keeping the body's internal environment stable, causing significant damage to cells (oxidative stress).

They observed that IVIG pre-treatment provided significant protection to brain cells that were subsequently exposed to ROS, making neurons less vulnerable to damage from reactive oxygen species.

"This is particularly important because we know that beta amyloid deposits in the Alzheimer's brain indirectly lead to the generation of ROS, including free radicals, that damage and destroy brain cells," Lahiri added.

Written by Dr. BelĂ©n Suarez  for The All Results Journals

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