Could an MIT team’s discovery one day restore the memories of Alzheimer’s patients?

Li-Huei Tsai, the director of MIT’s Picower Institute for Learning and Memory and the senior author on the study.Bryce Vickmark

Researchers at the Massachusetts Institute of Technology have made a discovery that could eventually lead to reversal of memory loss in Alzheimer’s patients, the university said.

The genes required to form new memories are unable to function in the brains of people with the devastating disease, contributing to a decline in their cognitive functions, the university said. The solution, MIT researchers believe, is to target the enzyme responsible for this genetic blockade: HDAC2.

The HDAC2 enzyme condenses the memory genes so tightly that it turns them off, the university said in a statement.

The problem that scientists have been facing for years is that so far, all the drugs that have been developed to attack this enzyme also affect other integral members of the HDAC family, leading to toxic side effects.

Now, for the first time, the team at MIT has found a way to target HDAC2 without blocking the other enzymes in the family, effectively reversing memory loss in the mice the technique was tested on.

“If we can remove the blockade by inhibiting HDAC2 activity or reducing HDAC2 levels, then we can . . . restore expression of all these genes necessary for learning and memory,” said Li-Huei Tsai, the director of MIT’s Picower Institute for Learning and Memory and the senior author on the study.

The researchers’ study appears in the Aug. 8 edition of “Cell Reports.”

There are about a dozen different types of the HDAC enzyme. Tsai has been able to identify HDAC2 as the form that affects genes related to memory, the university said. She has also found that people with Alzheimer’s and mice with models of the disease have increased levels of HDAC2 in their brains.

After testing postmortem brain samples, Tsai and her team pinpointed a gene called Sp3 that binds with HDAC2, which then results in the compression and subsequent deactivation of memory genes.

“This is exciting because for the first time we have found a specific mechanism by which HDAC2 regulates synaptic gene expression,” Tsai said in the statement.

When Tsai and her team lowered Sp3 levels in the mice they were testing, they found they were able to restore the mice’s ability to form long-term memories, according to the statement.

The researchers used a protein fragment made up of 90 amino acids to block Sp3 from binding with the HDAC2 enzyme.

The problem is that the fragment is probably too large to be used as a drug that could treat Alzheimer’s, the university said.

Now, researchers are faced with the challenge of finding a smaller protein that does the same job, or finding a chemical compound that would also prohibit Sp3 and HDAC2 from interacting, according to the university.

Tsai also plans to test this tactic for treating other disorders associated with HDAC2, which include post-traumatic stress disorder.