Multiple Sclerosis (MS) is an immune-mediated neurological disease that affects more than 2.3 million people worldwide (https://www.nationalmssociety.org/). This disease is caused by immune cells that are both adaptive (T & B lymphocytes) and innate (microglia). Together these cells promote inflammation, which damages the protective layer of nerve fibers known as the myelin sheath, nerves are unable to efficiently conduct electrical signals that translate messages to distant sites of the body, and ultimately the nerve fibers degenerate.

Common symptoms of MS are “pins and needles” or numbness of hands and feet, blurred vision, muscular weakness, impaired muscle coordination, incontinence, severe fatigue, and a large spectrum of neurocognitive disorders.

The Milner Group

Dr. Milner’s research studies focus on the design of new therapeutic approaches aimed at combating MS by increasing the blood supply to the brain and reducing vascular breakdown. Blood vessels in the CNS form the blood-brain barrier (BBB) which confers high electrical resistance and low permeability properties, thus protecting cells such as neurons and oligodendrocytes (myelin cells) from potentially harmful blood components. A strong BBB also helps reduce the influx of inflammatory immune cells into the CNS. The molecular basis of the BBB depends on: (i) inter-endothelial tight junction proteins, (ii) endothelial adhesion to the extracellular matrix (ECM) proteins of the underlying vascular basal lamina, and (iii) the influence of astrocyte end-feet and pericytes.

Recently, the Milner lab showed that low oxygen levels known as chronic mild hypoxia (CMH), accelerates clinical recovery in a preclinical model of MS, leading to long-term stable reduction in disease severity. Importantly, this protective effect of CMH was due to enhanced BBB integrity and accelerated cell death of the infiltrated immune cells. Ongoing studies are exploring ways of using this information to generate new approaches for treating MS. In other related projects, the Milner group is examining how specific cell adhesion mechanisms on CNS endothelial cells contribute to angiogenic remodeling (and thus increased vascularity) and BBB integrity. A more complete understanding of these mechanisms will facilitate future therapeutic strategies aimed at increasing vascularity and BBB integrity to combat the destructive effects of MS.

In addition to these focus areas, Dr. Milner also works in collaboration with Drs. Marcondes and Davies to try to understand how the different facets of the immune system interact to cause MS and its underlying relapses and remissions. Dr. Marcondes contributes knowledge on T cell immunology, the innate immune system, and the brain. Dr. Davies contributes knowledge on T cell immunology and the interactions between the immune system and other tissues.