BIO publishes quarterly newsletters for its members which focus on the therapeutic areas of member companies. The newsletters include updates from biotech stakeholders around Washington, including Congress, FDA, NIH, and patient organizations. The following is an excerpt from the "Focus on Neurology/CNS" newsletter. To find funding opportunities and learn about what Congress and the federal agencies are doing for biotechnology, please click here to read the “Focus on on Neurology/CNS" newsletter.
A repression of gene activity in the brain appears to be an early event affecting people with Alzheimer's disease, researchers funded by NIH have found. In mouse models of Alzheimer’s disease, this epigenetic blockade and its effects on memory were treatable.
“These findings provide a glimpse of the brain shutting down the ability to form new memories gene by gene in Alzheimer’s disease, and offer hope that we may be able to counteract this process,” said Dr. Roderick Corriveau.
Dr. Li-Huei Tsai and her team found that a protein called histone deacetylase 2 (HDAC2) accumulates in the brain early in the course of Alzheimer’s disease in mouse models and in people with the disease. HDAC2 is known to tighten up spools of DNA, effectively locking down the genes within and reducing their activity, or expression. In the mice, the increase in HDAC2 appears to produce a blockade of genes involved in learning and memory. Preventing the build-up of HDAC2 protected the mice from memory loss.
Dr. Tsai and her team examined two mouse models of Alzheimer's around the time that the mice begin to show signs of brain cell degeneration. They found that the mice had higher levels of HDAC2, but not other related HDAC proteins, specifically in the parts of the brain involved in learning and memory. This increase in HDAC2 was associated with a decrease in the expression of neuronal genes that HDAC2 regulates.
Use of a gene therapy approach to reduce the levels of HDAC2 prevented the blockade of gene expression. The treatment also prevented learning and memory impairments in the mice. It did not prevent neuronal death, but it did enhance neuroplasticity.
Dr. Tsai and her team also examined HDAC2 levels in autopsied brain tissue from 19 people with Alzheimer’s at different stages of the disease, and from seven unaffected individuals. Even in its earliest stages, the disease was associated with higher HDAC2 levels in the learning & memory regions of the brain.
“We think that the blockade of gene expression plays a very important role in the cognitive decline associated with Alzheimer's disease,” said Dr. Tsai. “The good news is that the blockade is potentially reversible.”
Dr. Tsai theorizes that HDAC2 is brought into play by beta-amyloid. Indeed, she and her team found that exposing mouse neurons to beta-amyloid caused them to produce more HDAC2.
For more information on this research, click here.
For more information, please click here to read the “Focus on Neurology/CNS” newsletter.