CAMBRIDGE, MA — A team of researchers at MIT have made a breakthrough in fighting memory loss associated with Alzheimer’s. After years of trial and error, their discovery has reversed memory loss in mice and could down the line help reverse memory loss in human Alzheimer’s patients, the university announced Wednesday.
Scientists have been looking at ways to manipulate an enzyme in the brain that causes a genetic blockage in the brains of people diagnosed with Alzheimer’s. The blockade contributes to the deterioration of cognitive abilities and shuts down the ability to form new memories by condensing them tightly, according to Massachusetts Institute of Technology researchers.
Until now, interfering with the enzyme (HDAC2) that forms the block has caused what scientists deem as toxic side effects and affected more than just that specific enzyme.
“If we can remove the blockade by inhibiting HDAC2 activity or reducing HDAC2 levels, then we can remove the blockade and restore expression of all these genes necessary for learning and memory," Li-Huei Tsai, director of MIT’s Picower Institute for Learning and Memory and the study’s senior author, said in a statement.
Blocking that mechanism could offer a new way to treat memory loss in Alzheimer’s patients.
In the study, released in the Aug. 8 issue of Cell Reports, the researchers used a large protein fragment to interfere with HDAC2, but they plan to look for smaller molecules that would be easier to deploy as drugs.
Tsai has been researching this for a while and has had several breakthrough revelations. In 2007, she first discovered that blocking HDAC activity could reverse memory loss in mice. Tsai later found that HDAC2 is responsible for the blockade of memory-linked genes. She also discovered that HDAC2 is elevated in human Alzheimer’s patients and in several mouse models of the disease.
“We think that HDAC2 serves as a master regulator of memory gene expression, and during Alzheimer’s disease it’s elevated so it causes an epigenetic blockade of the expression of those memory genes,” she said in a statement.
But she’s not done there.
Tsai also hopes to further investigate some genes known to correlate with HDAC2 in hopes of identifying other drug targets, according to the statement.
She also plans to look into whether her work could help people diagnosed with post-traumatic stress disorder and other disorders that involve elevated levels of HDAC2.
Hidekuni Yamakawa, Jemmie Cheng and Jay Penney are the lead authors of the study, and the research was funded by the Robert and Renee Belfer Family Foundation.
Image: MIT researchers have demonstrated a new way to reverse memory loss by blocking an enzyme known as HDAC2. Photo by Jose-Luis Olivares/MIT