Ariel Miller, MD, PhD
Associate Professor of Medicine/Neurology
MD, 1984 - Tel Aviv University
PhD, 1993 - The Hebrew University, Jerusalem
Immunomodulation, repair promotion, and pharmacogenetic-driven 'Personalized Medicine' in multiple sclerosis
Multiple sclerosis (MS), the most common neurological disease that afflicts young adults, is characterized by immune system attacks that destroy the myelin of the central nervous system, and results in various disabling neurological symptoms. Our research on the mechanisms of brain injury and repair includes studies on the activity of disease biomarkers and their inhibitors (such as the proteases matrix metalloproteinase, cathepsins), and the response to therapy in MS. We are investigating the potential role of a variety of treatments and repair promoting strategies for MS and other neurological disorders. An additional investigative area includes the genetic predisposition and environmental factors in MS, and focuses on the role of these factors in patients in diverse Israeli subpopulations. Our pharmacogenetic project integrates cutting-edge technology and bioinformatics for the genetic analysis of single nucleotide polymorphisms and gene expression profiles using a clinical database that includes the mode of response to therapy among MS patients. Our aim is to identify genomic and other biomarkers that correlate with a therapy response phenotype in order to develop a diagnostic kit for predicting the response to treatment. Our goal in this initiative is to improve medical care and clinical decision making in order to optimize drug prescribing, and to facilitate the translation of theranostics and genetics-based tailoring of treatment to the individual, the essence of ‘Personalized Medicine’.
Matrix metalloproteinase (MMPs) and their endogenous inhibitors (TIMPs) play key roles in the pathogenesis and repair of multiple sclerosis.
Advances in theranostics (pharmacogenetics, etc.) make it possible to prescribe safer and more effective therapies that are tailored to each patient’s unique genetic code.
Miller, A., Avidan, N., Tzunz-Henig, N., Glass-Marmor, L., Lejbkowicz, I., Pinter, R. Y., Paperna, T. 2008. Translation towards personalized medicine in Multiple Sclerosis. J Neurol Sci 274, 68-75.
Grossman, I., Avidan, N., Singer, C., Goldstaub, D., Hayardeny, L., Eyal, E., Ben-Asher, E., Paperna, T., Pe'er, I., Lancet, D., Beckmann, J. S., Miller, A. 2007. Pharmacogenetics of glatiramer acetate therapy for multiple sclerosis reveals drug-response markers. Pharmacogenet Genomics 17, 657-666.
Ben-Hur, T., Ben-Yosef, Y., Mizrachi-Kol, R., Ben-Menachem, O., Miller, A. 2006. Cytokine-mediated modulation of MMPs and TIMPs in multipotential neural precursor cells. J Neuroimmunol 175, 12-18.
Figure 1 (see description)
Figure 2 (see description)