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Our lab explores the nexus of metabolic failure and inflammation. Our approach is unique. We leverage insights from neurologic disorders with known single-gene mutations to unravel the molecular mechanisms of human neuroinflammation. Genetic disorders offer an unparalleled vantage point for understanding human biology. Immunogenetic are particularly unique because immune tissue is both accessible and modifiable. These disorders offer a unique window into basic molecular mechanisms and make exceptional targets for stem cell and gene therapies.Our team's goals are to:1. build foundational knowledge in human biology 2. develop transformational therapies for each disorder we study3. train the next generation of translational scientistsOur team draws purpose and inspiration from children and adults affected by neurodegenerative disorders. We are particularly focused on genetic and autoimmune disorders that cause damage to the myelin (the fatty insulation around the nerves) of the brain and spinal cord. X-linked adrenoleukodystrophy (genetic) and multiple sclerosis (autoimmune) are the prototypical examples of degenerative disorders of myelin; these are the two disorders we study most intensively.One of the great obstacles to understanding and treating MS is its pathological heterogeneity. MS is currently defined solely by clinical and radiological criteria. Although MS diagnostic criteria have improved over time, abundant evidence suggests that pathophysiologic "subtypes" of MS remain clinically indistinguishable. This pathophysiologic heterogeneity poses a major confounder to the development of new therapies. To combat this heterogeneity, we use ALD as a genetic model for MS. ALD is a rare (~1:17,00), monogenetic, X-linked disorder involving a gene (ABCD1) that encodes a peroxisomal protein. The biochemical hallmark of the disease is an accumulation of very-long chain fatty acids in several tissues, including myelin and blood. The ABCD1 mutation yields a variety of neuroendocrine symptoms, but the most feared manifestation is an inflammatory cerebral demyelinating syndrome known as "cerebral ALD" that affects ~40% of ALD boys. The absence of a clear genotype-phenotype correlation for cerebral ALD suggests a role for environmental modifiers, similar to MS. Despite the clinical and pathogenic similarities of MS and ALD, one question stands out: Why would a metabolic disorder like ALD yield a syndrome that so closely resembles MS, the prototypic neuroimmune disorder? This is the central questions animating our lab's current work.
A Pilot Study of Vitamin D in Boys With X-linked Adrenoleukodystrophy
In this pilot study, the investigators will assess the safety of two high-dose regimens of
oral vitamin D supplementation and measure the effects of vitamin D supplementation on
markers of oxidative stress and inflammation in the blood and brain of study participants
before, during, and after taking vitamin D supplements.
The goal of the study is to establish research measures (i.e. biomarkers) and an optimal dose
for vitamin D supplementation in boys with the X-linked adrenoleukodystrophy (ALD) genotype.
Stanford is currently not accepting patients for this trial.
For more information, please contact Keith Van Haren, MD, .
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