Multiple Sclerosis and Axon Injury: the new perspective

    13/06/2014

    MS Pic

    Multiple Sclerosis (MS) is a devastating disorder affecting more than two million people worldwide, occuring more commonly in women. It is an autoimmune disorder, which in susceptible individuals, results in the subject's own immune system attacking and damaging the myelin sheath of the nervous system, causing demyelination and neurodegeneration. Symptoms often include fatigue, numbness and tingling of arms and legs (ref. above picture of feet!), walking difficulties, vision problems, cognitive impairments, dizziness, pain and involuntary muscle spasms and paralysis.

    Typical nerve cell (neuron), wrapped in myelin, attacked by the patient's own immune defence (T-cells):

    Patients who suffer from MS often experience a primary phase of inflammation with relapse and remission followed by secondary progressive MS in later years. There is no cure for MS and it is unknown what triggers the initial onset of disease.

    Traditionally, people have speculated that the trigger could be genetic, environmental, exposure to other bacterial or viral infections, or even demographic. However, MRI scans of some patients reveal a new sub-class of MS called normal-appearing white matter (NAWM) in which myelin is NOT damaged and injury correlates with diffuse inflammation in the brain:

    Typical MRI scans of MS patients' brains showing black holes:

    Increasingly it has been found that axon loss can occur early on in the disease, in unmyelinated axons of the grey matter, or in the retinal nerve fibre layer of the optic nerve. This paves the way for a new hypothesis: that MS is primarily a disease of axon injury and neurodegeneration. An article published in Nature Reviews Neurology this year delved into the mechanism of axon injury. These situations are rather similar to damage from a stroke, or to long-term spinal cord injury sufferers. Here is a fancy diagram showing a myriad of ways an axon can be damaged:

    MS neuron

    Molecular mechanisms that cause axon damage can essentially include:

    * Inflammation by macrophages and microglia which cross from the blood to the brain

    * Oxidative stress, caused by free radicals, generated by inflammation

    * Mutations in mitochondrial DNA, generating more free radicals and causing loss of ATP (the body's energy molecule)

    * Ion channel dysfunction caused by excess Calcium and Sodium ion influx into the neuron

    * Apoptosis by Wallerian Degeneration (a process where the axon dies back and the neuron eventually dies)