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Mouse Study Shows Inhibiting Enzyme Can Reverse Myelin Damage and Improve Limb Function

February 26, 2018

Damage to the myelin sheath typically tends to be the cause of multiple sclerosis related problems such as muscle stiffness and weakness, fatigue, and pain. A team of researchers at the Cincinnati Children’s Hospital Medical Center conducted an MS-related study in mice that could reverse damage done to the myelin sheath, which is what protects nerve cells and improves limb function. This can be done by inhibiting an enzyme that is responsible for turning on genes on and off.

The research involved mice with a sciatic nerve damage instead of MS, and is called “A histone deacetylase 3-dependent pathway delimits peripheral myelin growth and functional regeneration.”

The turning-on and –off process does not interfere with a gene’s DNA sequence; it has been dubbed by scientists to be an epigenetic regulation. It works by adding or removing an epigenetic mark from a DNA sequence, similar to the process of one adding or removing something like a clothes pin.

Compounds thought to have potential in mice with injured sciatic nerves, which run from the lower back to lower legs, were tested by the team.  Many of these compounds were approved cancer treatments.

Compounds that could inhibit a particular epigenetic enzyme, histone deacetylase 3 or HDAC3, were found to reverse the mice’s myelin damage and improve their ability to move. The enzyme slows down myelin production when nerves are forming or after they have been injured.

The braking leads to the formation of an extremely thin layer of myelin, or in some cases, it leads to no layer at all. Communication is then impaired between the peripheral nervous system—which consists of all nerves outside of the brain and spinal cord—and the limbs and organs.

The director of the Cincinnati Children’s Brain Tumor Center, Dr. Q. Richard Lu said in a press release that the temporary inhibition of HDAC3 had vigorously accelerated the formation of myelin which helps insulate peripheral nerves. Lu also said, “This promoted functional recovery in the animals after peripheral nerve injury.”

Although, researchers said blocking HDAC3 must be done precisely, as inhibiting for too long leads to excessive myelin growth, which results in overly thick nerve cell insulation which can cause functional problems.

The team timed their HDAC3 inhibitor treatment so it would lead to just enough myelin needed in order to restore the mice’s function.

Researchers have begun testing their findings in mouse models for diseases such as MS which are caused by myelin damage. They plan to start Phase 1 clinical trials of the treatment in MS patients if the results are promising.