Inhibiting HDAC1 Enzyme Prevents Mice from Developing MS-like Disease, Study Finds

Inhibiting an enzyme prevented mice from developing a multiple sclerosis-like disease, a European study reports.

The finding about HDAC1, a member of the histone deacetylases family of enzymes, could open up new therapy possibilities for MS.

Researchers published their study, “A T cell-specific deletion of HDAC1 protects against experimental autoimmune encephalomyelitis,” in the Journal of Autoimmunity. 

Dr. Wilfried Ellmeier, a professor at the Institute of Immunology in MedUni Vienna, Austria, led the research effort, which was supported by the European Union and the Austrian Science Fund.

HDAC enzymes are responsible for which genes are turned on and which are turned off. A gene that is turned on will generate proteins, while one turned off will not.

Eighteen HDACs take part in the epigenetic process of turning genes on or off. In addition to regulating gene activity, they can change the activity and function of proteins. The bottom line is that they play a major role in regulating a cell’s behavior.

Previous studies have demonstrated that HDACs are particularly important to the regulation of immune T-cells’ response and communication. The research has also shown that inhibiting the enzymes diminishes immune response in mouse models, including mice with autoimmune encephalomyelitis (EAE), an animal model of human multiple sclerosis.

The role that different HDAC family members play in the development of autoimmune disorders such as multiple sclerosis has been unclear, however.

So European researchers decided to look into it. They found that mice whose immune T-cells lacked HCAC1 did not develop EAE.

This suggested that HDAC1 is essential to the autoimmunity that T-cells trigger in mice with a multiple sclerosis-like disease. An autoimmune disease is one in which immune cells attack healthy cells in the body instead of invaders.

“We still do not know the underlying mechanism responsible for this protective effect,” Ellmeier said. “We now want to conduct follow-on studies to discover the molecular details.”

Doctors use HDAC inhibitors to treat certain types of cancer. Researchers have suggested they also could be used to treat autoimmune diseases like MS.

A drawback of inhibitors is that they generate serious side effects. The European study suggested that inhibitors that target HDAC1 in T-cells may generate fewer side effects. That would make it a potential treatment for multiple sclerosis, lead author Lisa Göschl said.

Studies need to be done to confirm this hypothesis, the team said.