Can myelin be restored?
Autoimmune diseases are a group of diseases, the main difference of which is the attack of the immune system of its own cells and tissues. In the case when the target for immune cells is peripheral nerve tissue, irreversible damage occurs to myelin – the insulating layer surrounding the nerve fiber, feeding it and providing rapid transmission of nerve impulses. Patients complain of persistent pain in the extremities. Unfortunately, there are no effective ways to treat this pathology.
Researchers from the Cincinnati Children's Hospital Medical Center (USA) describe an experimental molecular therapy that restores the myelin layer of peripheral nerves in mice and improves limb functions.
Scientists have performed epigenetic screening of compounds that suppress enzymes involved in chromosomal changes. Their goal was to influence the regulation of gene activity in cells. A suitable compound has been identified – it is a drug previously approved for the treatment of certain types of cancer. It was tested on mouse models with sciatic nerve damage.
The application point of the tested compound was the enzyme histone deacetylase 3 (HDAC3). This enzyme is found in mice and humans. It has previously been proven that it blocks the remyelination of peripheral nerves: after damage to the insulating myelin layer, HDAC3 leads to epigenetic (unrelated to DNA sequence changes) changes in chromosomes and limits the synthesis of the myelin protein. As a result, the defect of the myelin layer is closed by too thin a layer of myelin or does not close at all. The process of transmitting an impulse along such a nerve slows down or stops.
Proliferation of Schwann cells (green) synthesizing myelin (red) against the background of blocking the HDAC3 enzyme. Source: article in Nature Medicine.
Inhibition of HDAC3 led to an acceleration of myelin synthesis by Schwann cells. This contributed to the restoration of the motor function of the injured limb of the mice.
The authors note that the duration of treatment is of critical importance. In the experiment, mice were injected with the drug for a certain period of time: prolonged inhibition of the HDAC3 enzyme led to excessive growth of the myelin sheath, which also leads to a violation of the transmission of impulse along the nerve.
In order to move from theory to practice and introduce the remyelination method into clinical medicine, a large amount of work needs to be done: new research needs to be conducted to study it in conditions as close as possible to the human body. The researchers also plan to evaluate the effectiveness of the technique in demyelinating diseases of the central nervous system, in particular, multiple sclerosis.
Article by Xuelian He et al. A histone deacetylase 3–dependent pathway delimits peripheral myelin growth and functional regeneration is published in the journal Nature Medicine.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru Based on Cincinnati Children's materials: Experimental Therapy Restores Nerve Insulation Damaged by Disease.