Abstract

Multiple sclerosis (MS) relapses are known to be significantly decreased during pregnancy. This proposal will establish whether oral treatment with estriol, the major estrogen of pregnancy, induces a decrease in relapses in relapsing remitting multiple sclerosis (RRMS) subjects when used in combination with injectable Copaxone. Previously, in a pilot study, it has been demonstrated that treatment of RRMS subjects with oral estriol for six months resulted in a significant reduction in gadolinium enhancing lesions on serial brain MRIs (Annals of Neurology, 2002; 52:421-428) and caused a favorable shift in immune responses (Journal of Immunology, 2003; 171:6267-6274). This is an add-on study aiming to extend these previous findings by treating longer and focusing on clinical outcomes. The combination of Copaxone injection plus estriol pill (8 mg per day) will be compared to Copaxone injection plus placebo pill in a double blind trial. The duration of treatment will be two years and the primary outcome measure will be relapse rate. Secondary outcomes will include disability measures (MSFC, EDSS, 7-24 MS Quality of Life, Modified Fatigue Impact Scale and Beck Depression Inventory) and MRI surrogate biomarkers for relapses (enhancing lesions, new T2 lesions) and disability (atrophy, T1 holes). Safety measures (blood tests and gynecologic evaluations) will also be followed. The overall goal of this study will be the development of an oral treatment, estriol, for RRMS. ? ? ?

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS051591-02
Application #
7471402
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Program Officer
Utz, Ursula
Project Start
2007-08-01
Project End
2010-04-30
Budget Start
2008-05-01
Budget End
2009-04-30
Support Year
2
Fiscal Year
2008
Total Cost
$500,000
Indirect Cost

  Institution

Name
University of California Los Angeles
Department
Neurology
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095

  Publications

MacKenzie-Graham, Allan; Brook, Jenny; Kurth, Florian et al. (2018) Estriol-mediated neuroprotection in multiple sclerosis localized by voxel-based morphometry. Brain Behav 8:e01086
Voskuhl, Rhonda (2018) It is time to conduct phase 3 clinical trials of sex hormones in MS - Yes. Mult Scler 24:1413-1415
Itoh, Noriko; Kim, Roy; Peng, Mavis et al. (2017) Bedside to bench to bedside research: Estrogen receptor beta ligand as a candidate neuroprotective treatment for multiple sclerosis. J Neuroimmunol 304:63-71
Ziehn, Marina O; Avedisian, Andrea A; Dervin, Shannon M et al. (2012) Estriol preserves synaptic transmission in the hippocampus during autoimmune demyelinating disease. Lab Invest 92:1234-45
Naismith, Robert T; Xu, Junqian; Tutlam, Nhial T et al. (2012) Diffusion tensor imaging in acute optic neuropathies: predictor of clinical outcomes. Arch Neurol 69:65-71
Spence, Rory D; Voskuhl, Rhonda R (2012) Neuroprotective effects of estrogens and androgens in CNS inflammation and neurodegeneration. Front Neuroendocrinol 33:105-15
Voskuhl, Rhonda R; Gold, Stefan M (2012) Sex-related factors in multiple sclerosis susceptibility and progression. Nat Rev Neurol 8:255-63
Sicotte, Nancy L (2011) Neuroimaging in multiple sclerosis: neurotherapeutic implications. Neurotherapeutics 8:54-62
Naismith, R T; Xu, J; Tutlam, N T et al. (2010) Increased diffusivity in acute multiple sclerosis lesions predicts risk of black hole. Neurology 74:1694-701
Cross, Anne H; Parks, Becky Jo (2010) The four seasons of multiple sclerosis. Neurology 75:762-3

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