Stefan Gold, Ph.D.

Scientific summary:
There is a distinct female preponderance of autoimmune diseases including multiple sclerosis (MS), suggesting a role for sex hormones and/or chromosomes in disease susceptibility. In vitro and experimental data indicate that testosterone may exert beneficial effects in inflammatory autoimmune disease by shifting immune responses from a Th1-like pattern towards Th2 and testosterone treatment has been found to ameliorate animal models of MS and other Th1-like autoimmune diseases. Furthermore several lines of evidence indicate that testosterone may have neuroprotective properties. Indeed, in a pilot study enrolling 10 male patients with relapsing-remitting MS (RRMS), daily treatment with 100mg of testosterone (transdermal) over 12 months was associated with preservation of cognitive function as well as a slowing of brain atrophy rate as measured by MRI compared to a pretreatment observation period. Furthermore, delayed type hypersensitivity (DTH) skin tests showed reduced responses during treatment. These findings suggest a possible immunomodulatory as well as a neuroprotective effect of testosterone in multiple sclerosis. The project aims to investigate the effects of testosterone treatment on cytokine and neurotrophic factor production by immune cells obtained from the patients before and during the trial to gain insight into mechanisms underlying the protective effects of testosterone treatment in this trial. We will study cytokine (IL-2, IL-5, IFN-gamma, TNF-alpha, IL-10, IL-12p40) and growth factor (TGF-beta, bNGF, BDNF, CNTF, PDGF, bFGF) production in supernatants from ex vivo mitogen stimulated cultures of peripheral blood mononuclear cells (PBMCs). Correlations between changes in protein production and atrophy rate and cognitive scores over the course of the treatment period will be determined. We will further use flow cytometry and intracellular staining to examine the cell subpopulations responsible for alterations in cytokine and growth factor production. Finally, in vitro CNS cell cultures exposed to PBMC supernatants will be used to investigate the functional significance and gain mechanistic insight in how cytokines and neurotrophic factors from immune cells may influence CNS cell survival.

Stefan received his B.S. in psychology from the University of Giessen and his M.S. in clinical psychology and immunology from the University of Hamburg in Germany. For his doctoral thesis project, he worked Dr. Dana Bovbjerg’s immunology laboratory at Mt. Sinai School of Medicine in New York City (2001-2002). Upon completion of his PhD in 2003, he started a post-doctoral position at the NYU Neuroimaging Laboratory, Department of Psychiatry, under the mentorship of Dr. Convit with a fellowship from the German Research Society. He joined UCLA in 2005. Stefan’s main research interest focuses on endocrine immunoregulation in multiple sclerosis (MS). He is particularly interested in how disruptions of the communication between those systems can contribute to MS disease pathogenesis and progression. In his project, he uses an array of methods and techniques from cellular immunology and in vitro CNS cell culture models to MRI and neuropsychology to investigate the mechanisms and clinical implications of endocrine immune interactions in MS.