Current Research and Scholarly Interests
We have three primary areas of interest:
1. Development of diagnostic and therapeutic biomarkers for multiple sclerosis (MS) and X-linked adrenoleukodystrophy (ALD)
2. Improved understanding of the role of lipid metabolism and oxidative stress in myeloid cells in the pathogenesis of MS and ALD. We are currently exploring the role of vitamin D in regulating myeloid cell pathology.
3. Clinically, we are interested in developing innovative care strategies for patients with demyelinating disorders.
One of the great obstacles to understanding and treating MS is it's pathological heterogeneity. MS is currently defined solely by clinical and radiological criteria. Although these criteria have improved over time, abundant evidence suggests that pathophysiologic "subtypes" of MS still exist and, moreover, are indistinguishable from one another using current diagnostic criteria. Because potential differences in MS pathogenesis may result in divergent responses to the same treatment, this pathogenic variability poses serious hurdles to developing and implementing treatment strategies for affected patients.
The inflammatory cerebral demyelination of ALD represents a potential genetic model for MS. ALD is a monogenetic, X-linked disorder involving a gene (ABCD1) that encodes a peroxisomal protein. The incidence is ~1:17,000. The biochemical hallmark of the disease is an accumulation of very-long chain fatty acids in several tissues, including myelin and blood. Cerebral demyelination occurs in only a subset of patients, but is not related to genotype, suggesting a role for environmental modifiers, much like MS.
Our group has recently identified serum vitamin D status as the first known risk factor for the onset of the inflammatory demyelinating phenotype of ALD. This has implications for both pathogenesis and therapy and is further evidence of pathogenic overlap with MS, where risk is also predicted by serum vitamin D status. We are currently exploring the role of vitamin D at the macrophage-myelin interface. We are also developing data to support a clinical trial studying vitamin D as a preventive therapy in ALD boys without inflammatory demyelination. This observation stands to shed important light on the role of vitamin D in both ALD and MS.