Axon Damage May Precede Myelin Damage
It has recently been discovered that axons, or nerve cells, can start degenerating spontaneously without prior damage to their protective myelin coating. If found and treated early, this process can be reversed in mice, which may lead to new effective treatments for MS, according to the findings of a study published in Nature Medicine.
In the paper, senior authors professor Martin Kerschensteiner of the Ludwig-Maximilians-Universität in Munich, Germany, and professor Thomas Misgeld from the Technical University of Munich, and colleagues describe how they found a previously unknown type of axon or nerve cell degeneration, which they call "focal axonal degeneration" (FAD).
While the discovery opens the door to new drug targets, the researchers warn there is still a lot of work to be done before effective treatments are available, as Kerschensteiner explained:
"As yet, we only have a superficial understanding of the underlying molecular mechanisms and, of course, finding effective therapies will require time-consuming screens and extensive trials of drug candidates," he cautioned.
Autoimmune diseases like MS occur when the immune system, which normally only targets and destroys foreign agents such as toxins, bacteria and viruses, that have entered the body, instead attacks the body's own tissue, causing inflammation and eventually degeneration of the area affected.
The predominant view is that axon damage in MS follows the gradual destruction of the myelin sheath, the protective, electrically insulating coating of tissue surrounding the axon that speeds up the transmission of signals.
What triggers the axon damage itself, however, is poorly understood, and it was this that Kerschensteiner and Misgeld were trying to learn more about using lab mice when they made their surprising finding.
The finding may explain why some patients with MS experience spontaneous remission of symptoms:
"In its early stages, axonal damage is spontaneously reversible," said Kerschensteiner. "This finding gives us a better understanding of the disease, but it may also point to a new route to therapy, as processes that are in principle reversible should be more susceptible to treatment."
“However, before any potential drugs can even be considered, never mind put forward for trial, we need a much better understanding of the underlying molecular chemistry and biology of a disease.”
Previous studies of MS have already suggested that reactive oxygen and nitrogen radicals, chemicals produced by the immune system, play an important part in destroying axons. The researchers suggest in the case of FAD, these aggressive chemicals attack the mitochondria inside the nerve cells. Mitochondria are the "power cells" inside cells, they synthesize ATP molecules, the universal "currency units of energy" with which cells build, maintain and operate themselves.
In the lab mice, they were able to take action to rescue axons that had already started degenerating.
And in a final stage of their study, they found characteristic signs consistent with FAD in brain tissue from humans with MS, giving hope that the same treatment principles they established in the mice might also work in humans.
I find this to be VERY interesting, considering the fact that I have only ever been told that MS is the result of the immune system attacking the myelin, thus damaging the body's ability to properly transmit the neurons. It is very intriguing to now learn that the axons may be damaged without damage to the myelin sheath! I cannot wait to learn more about this research!