Multiple Sclerosis


To contact the MS program, the direct contact is:
Michael J. Montag
MMontag@mednet.ucla.edu
(310) 206-2176
 
Schedule a patient in the MS clinic:
Laura C. Andrade, LVN
LCAndrade@mednet.ucla.edu
(310) 206-0452
 
To contact the MS laboratories:
Noriko Itoh, BS, MS
NIto@mednet.ucla.edu
(310) 206-4640
 
To discuss making a donation:
Office Phone: (310) 206-6749

Elizabeth Naito
enaito@support.ucla.edu
or
Karin Colimore
kcolimore@support.ucla.edu


 

Read more:
Lancet Neurology Estriol Trial Publication Jan 4, 2016
http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(15)00322-1/abstract

NPR "All Things Considered" Feb 10, 2016
http://www.npr.org/sections/health-shots/2016/02/10/464697905/a-fix-for-gender-bias-in-animal-research-could-help-humans

Multiple Sclerosis Discovery Forum Feb 6, 2016
http://www.msdiscovery.org/news/essays_opinions/26395-taking-studies-sex-differences-next-level

NPR “Morning Edition” June 2, 2014
http://www.npr.org/sections/health-shots/2014/06/02/317355068/pregnancy-hormone-may-reduce-multiple-sclerosis-symptoms

   
MS We were the first one to prove the clinical observation in laboratory studies that females were more susceptible to multiple sclerosis than males.  We continued studying sex differences that included testosterone in men and the pregnancy hormone, estriol, in women for multiple sclerosis.  We kept finding similar outcomes.  Both were anti-inflammatory and neuro-protective.  Our clinical trials for estriol in women to reduce relapses and cognitive degeneration are in Phase III planning now and testosterone for men in Phase II.

Mission:

To improve the lives of patients suffering from multiple sclerosis.

Overview

The Multiple Sclerosis (MS) Program at UCLA aims to improve the lives of MS patients by developing new therapies for MS and by providing expert clinical care. This is accomplished through basic science in genetics, immunology and central nervous system biology, highly advanced neuroimaging, novel therapeutic trials and a full spectrum of clinical care from inpatient to novel outpatient programs. MS patients are seen by dedicated specialists with decades of combined experience and/or fellowship training in the diagnosis and treatment of this difficult disease. UCLA is a designated MS Comprehensive Care Center.

The Marilyn Hilton Multiple Sclerosis Achievement Center at UCLA

As an adjunct service to the diagnostic, treatment and consultative services provided, UCLA also offers access to this unique center that provides rehabilitative, recreational, and education services in a small group setting. The center, a joint effort of the National Multiple Sclerosis Society and the UCLA Department of Neurology, offers a broad continuum of care that will complement the medical management of MS.

The Team

A major strength of the UCLA MS Research Program lies in its collaborations with scientists beyond the UCLA Department of Neurology, to capture the extraordinary expertise of the UCLA Neuroscience community and focus this tremendous pool of minds on finding a cure for MS. This is who we are:

Dr. Rhonda Voskuhl, Professor, Dept. of Neurology, is the Jack H. Skirball Chair in MS Research and Director of the MS Program at UCLA. She is an internationally recognized expert in MS, focusing on translational work by moving from the bedside (clinical observations) to the bench (research) to the bedside (novel clinical trials). She has had two novel agents in four treatment trials for MS completed or underway based on results from her research. In 2013 and 2014, Dr. Voskuhl was one of five finalists for the Barancik Prize from the National MS Society, an award recognizing the Most Innovative MS Researcher in the World. Dr. Voskuhl's patient care focus is giving second opinions on diagnosis of complex cases as well as on major changes in MS treatment management. She also trains post doctoral fellows, graduate students and undergraduates in clinical and preclinical MS.

Dr. Barbara Giesser, Professor, Dept. of Neurology, is clinical director of UCLA MS Clinical Services, specializing in MS patient care. The clinical program offers many treatments that can impact disease course, ameliorate symptoms, improve function, and enhance quality of life. Her direction has been central to establishing UCLA as an MS Comprehesive Care Center. She also designed a clinical trial related to exercise in MS.

Dr. Allan MacKenzie-Graham, Ph.D., Asst. Professor, Dept. of Neurology, is a neuroimaging expert in MS who is a faculty member of the UCLA Brain Mapping Center. He has done seminal work in showing a halting of brain atrophy in women in the estriol clinical trial and in men in the testosterone clinical trial. In addition, he was the first to show that brain atrophy occurs in the most widely used MS model in the world, creating a tool to screen drugs to halt this atrophy.

Dr. Callene Momtazee, Dept. of Neurology, specializes in MS patient care and provides consultative, diagnostic and management services. She has particular interest in neuromyelitis optice (NMO), a variant of MS. She has also been involved in MS trials at UCLA.

Dr. Yuichiro Itoh, Asst. Professor, Dept. of Neurology, specialized in genetic analysis and bioinformatics. He is determining how gene expression changes in each cell type in the brain during disease in the MS model and is translating these gene expression change toward developing a new treatment for MS. His current work aims to discover whether localized gene expression differences in specific cells in the brain are responsible for the differences in types of disabilities that MS patients have.

Dr. Michael Sofroniew, M.D., Ph.D., Professor, Dept. of Neurobiology, UCLA, an expert in neuroscience, glial biology and genetic engineering of molecules in specific cells within the brain. His work reveals the biology of cells in the brain during MS thereby suggesting new treatment targets.

Dr. Thomas O'Dell, Professor, Dept. of Physiology, UCLA, an expert in synaptic plasticity and electrophysiologic function to assess the cognitive area of the brain. His work reveals mechanisms of cognitive disability in MS, thereby suggesting new treatments to reverse this.

Dr. Arthur Arnold, Professor, Dept. of Integrative Biology & Physiology, an expert in the effect of sex hormone and sex chromosome effects on the brain. His expertise has been central to understanding sex differences in MS.

Dr. Robert Elashoff, Professor, Dept. of Biomathematics, UCLA, an expert in clinical trial design, management and trial statistical analysis. His team has been responsible for data management across multiple sites and statistical analysis of all 4 clinical trials in MS with UCLA as the lead site.

Post doctoral fellows in the MS Program:
Dr. Marway Kalsey, M.D., MS patient care
Dr. Alessia Tassoni, Neurobiology of visual disability in MS
Dr. Stefano Lepore, MS model neuroimaging

Graduate students in the MS Program:
Roy Kim, Ph.D. candidate, next generation estrogen treatments for MS
Laura Kammel, Ph.D. candidate, neuroscience of cognitive disability in MS
Lisa Golden, Ph.D. candidate, the role of maternal versus paternal inheritance in MS
Cassandra Meyer, Ph.D. candidate, neuropathology in 3-D using CLARITY in MS

Nurses in the MS Program:
Elise Herlihy, RN
Kirstin Nygren, NP
 

Laboratory Technicians in the MS Program:
Noriko Itoh, B.S., M.S., Administrator and Supervisor
Hadley Johnsonbaugh, B.S.
 

The Research Approach: BEDSIDE TO BENCH TO BEDSIDE

A UNIQUE APPROACH TO CLINICAL TRIALS AT UCLA -- Rather than the classic “Bench to Bedside” research approach where investigations begin with a molecule of interest or a lab technique, we have successfully implemented a “Bedside to Bench to Bedside” approach whereby investigations begin with a clinical observation. This approach greatly increases the probability that a finding at the bench will ultimately be significant in MS patients simply because we begin with a clinical observation known to be important in MS. We investigate the clinical observation’s underlying mechanism at the bench, and then translate this back to MS patients in the form of a clinical trial. In the past we have focused on the observations that “MS is better during pregnancy” and “There are sex differences in MS”. This has lead to four successful clinical trials thus far, two pilot trials at UCLA and two multicenter trials with UCLA the lead site, all with Dr. Voskuhl the Principle Investigator and without ownership or control by a pharmaceutical company. Findings of the most recent trial are in press with Lancet Neurology, the most highly ranked neurology journal in the world. In this publication the clinical observation that pregnancy is protective in MS (bedside), led to the identification of estriol as a protective hormone of pregnancy (bench), which led to a clinical trial testing estriol treatment in women with MS (bedside) showing beneficial effects on relapses, cognition, fatigue and brain atrophy. New investigations are based on the clinical observation that disabilities vary greatly from one MS patient to the next. This clinical observation is central to why it has been so difficult for MS researchers to find a neuroprotective treatment over the last decade. They do not account for these differences in disabilities in their approach. Here, we will embrace these differences in disabilities as a major clinical observation to be unraveled and understood at the lab bench for subsequent translation back to the bedside in the form of clinical trial.

Safe form of estrogen helped Multiple Sclerosis patients avoid relapses in UCLA led clinical trial

The Next Steps – Summary of Projects

Our goal is to harness the tremendous neuroscience expertise at UCLA to find a neuroprotective treatment to repair disability in MS. We will undertake a new approach that is highly sophisticated, while grounded in a key clinical observation, together providing an elegant and paradigm shifting approach.

  • We are now unraveling neurological pathways in the MS model to discover novel treatments for each disability. Here, we will focus on a new clinical observation, which is: “Disabilities vary greatly from one MS patient to the next”. This is particularly true at the earliest stages of disability progression. Some patients start mostly with walking disability and very little visual or cognitive disability. Others have mostly visual disability with very little cognitive or walking disability, while still others have cognitive disability with very little visual or walking disability. Central to our approach is the fact that the brain and spinal cord are not composed of uniformly organized homogeneous cells, and are much more complex than a “target organ of an autoimmune attack” as described extensively by immunology based MS researchers. The neuroanatomy, cell types, neurotransmitters, neurotrophic factors and function for each neurological pathway differs. For example, the neurological pathway for leg strength is different from cognition and vision; while the pathway for cognition is different from those involved in leg strength and vision, and so on. An unfortunate likelihood is that a treatment that optimally preserves or repairs leg strength may be different from a treatment that optimally preserves or repairs cognitive ability, which may, in turn, be different from one for vision. It is unlikely that there will be a silver bullet treatment to repair all disabilities in MS. The “one size fits all” approach is untenable given the known differences in neurological pathways. Here, we will capitalize on these differences to develop treatments that are tailored to optimally repair each disability. Importantly, these will not merely be symptomatic treatments for temporary improvement. Rather, these will be major disease modifying treatments focused on halting or reversing the processes leading to each disability.
  • We are raising funds for a large multicenter trial of testosterone treatment for men with MS, similar to that just successfully completed for estriol for women with MS.
  • Using the MS model, we have identified a gene on the X chromosome that is expressed in the brain that may help us understand why men tend to have a more progression course of disease. Finding new treatments to regulate this gene may lead to a treatment that will halt disease progression, with relevance to other neurodegenerative diseases that demonstrate gradual progressive worsening.
  • Using the MS model, we have identified a gene on the X chromosome that is expressed in immune cells that may contribute to why women are more susceptible to developing MS and what contributes to relapses. Finding new treatments to modulate this gene may lead to a treatment that will reduce relapsing disease, with relevance to other autoimmune diseases characterized by an increased susceptibility in females.
  • We are studying the relative contribution of maternal versus paternal inheritance of genes involved in MS susceptibility and progression.
  • In our recently completed multicenter trial of estriol in women with MS where we found significant beneficial effects on relapses and cognition, we acquired brain MRI scans. These MRI scans now need to be assessed for which region of the brain estriol treatment had the greatest effect impact on halting gray matter atrophy and with correlation to improvement in each disability.
  • A trial focusing on whether estriol treatment can improve cognition in not only RRMS, but also in progressive MS is needed. We have begun that trial, and it is ongoing at 4 sites across the U.S. Based on our results in the relapse trial, we know that this new trial is on target with regard to its optimal design and outcomes. In this trial, estriol treatment can be added on to other standard of care MS treatments (not just Copaxone, but also interferons or the new orals) or estriol can be used in people on no other MS treatments. The treatment duration is one year, and the primary outcome is cognitive testing.
  • We are raising $15 million and have designed the next estriol trial as required by the FDA to bring estriol to the market in the U.S.

 

The Investment In The Future: Education

In addition to doing the MS work above, the UCLA MS Program is training the next generation of MS doctors. At any given time there are approximately 2-4 post doctoral fellows, 3-5 graduate students, and 10 undergraduates, as well as high school students in the summer, who are all being trained. Support for these students for only one year can provide time for them to apply for outside funding for 3 additional years support, thereby amplifying the investment in their future, and in the future of MS research.

Investment In Infrastructure: Optic Neuritis

In September of 2015, we recruited an expert in the visual system (Dr. Alessia Tassoni) who comes from the world renowned visual laboratory of Dr. Keith Martin, Cambridge, UK. In order to develop a novel treatment focused specifically on helping patients with optic neuritis, we need to raise $180,000 to buy an Ocular Coherence Tomography machine (OCT). OCT is used frequently in MS to demonstrate neurodegeneration of the visual pathway. By using OCT in our model of MS we will not only be able to better understanding why visual disability occurs, but will also be able to screen new treatments their ability to repair visual loss.

The Request

The UCLA MS program owes much of its success to the philanthropic support it has received over the years for its highly innovative projects. Support of these highly innovative projects in their infancy has been critical in generating the results needed to later move projects into more traditional mechanisms of funding from the NIH and NMSS. Philanthropic supporters have included, but are not limited to, the Conrad N. Hilton Foundation, the Jack H. Skirball Foundation, the Sherak Family Foundation, the Tom Sherak MS Hope Foundation, the Gustafson Foundation, DirecTV, the Safan Family Foundation, the Diamont Foundation, the Zamucen Foundation and the Elks Club. Without the support of these visionary partners, the achievements of the UCLA MS Program would not have been possible.

We request that you partner with us at UCLA in this paradigm shifting approach to find neuroprotective treatments to improve disabilities in MS by giving online today, or for more information, please contact Pamela Thompson at (310) 267-1837.

References

  1. Voskuhl, R.R., et al. Estriol combined with glatiramer acetate for relapsing-remitting multiple sclerosis: a randomised, placebo-controlled, phase 2 trial. Lancet Neurology (2015).
  2. Du, S., et al. XY sex chromosome complement, compared with XX, in the CNS confers greater neurodegeneration during experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A 111, 2806-2811 (2014).
  3. Kim, R.Y., et al. Astrocyte CCL2 sustains immune cell infiltration in chronic experimental autoimmune encephalomyelitis. J Neuroimmunol 274, 53-61 (2014).
  4. Kurth, F., et al. Neuroprotective effects of testosterone treatment in men with multiple sclerosis. Neuroimage Clin 4, 454-460 (2014).
  5. Ghandour, M.S., Voskuhl, R.R. & Schumacher, M. The androgen receptor as a therapeutic target for myelin repair in demyelinating disease. Expert Review of Endocrinology and Metabolism (2013).
  6. Spence, R.D., et al. Estrogen mediates neuroprotection and anti-inflammatory effects during EAE through ERalpha signaling on astrocytes but not through ERbeta signaling on astrocytes or neurons. J Neurosci 33, 10924-10933 (2013).
  7. Wisdom, A.J., Cao, Y., Itoh, N., Spence, R.D. & Voskuhl, R.R. Estrogen receptor-beta ligand treatment after disease onset is neuroprotective in the multiple sclerosis model. J Neurosci Res 91, 901-908 (2013).
  8. Daumer, M., Weinshenker, B.G. & Voskuhl, R. Pregnancy: a "modifiable" risk factor in MS? Neurology 78, 846-848 (2012).
  9. Gold, S.M., et al. Dynamic Development of Glucocorticoid Resistance during Autoimmune Neuroinflammation. J Clin Endocrinol Metab 97, E1402-1410 (2012).
  10. MacKenzie-Graham, A., et al. Cortical atrophy in experimental autoimmune encephalomyelitis: in vivo imaging. Neuroimage 60, 95-104 (2012).
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  12. Sasidhar, M.V., Itoh, N., Gold, S.M., Lawson, G.W. & Voskuhl, R.R. The XX sex chromosome complement in mice is associated with increased spontaneous lupus compared with XY. Ann Rheum Dis 71, 1418-1422 (2012).
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  14. Voskuhl, R.R. & Gold, S.M. Sex-related factors in multiple sclerosis susceptibility and progression. Nat Rev Neurol 8, 255-263 (2012).
  15. Ziehn, M.O., Avedisian, A.A., Dervin, S.M., O'Dell, T.J. & Voskuhl, R.R. Estriol preserves synaptic transmission in the hippocampus during autoimmune demyelinating disease. Lab Invest 92, 1234-1245 (2012).
  16. Ziehn, M.O., et al. Therapeutic Testosterone Administration Preserves Excitatory Synaptic Transmission in the Hippocampus during Autoimmune Demyelinating Disease. J Neurosci 32, 12312-12324 (2012).
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  22. Du, S., Sandoval, F., Trinh, P. & Voskuhl, R.R. Additive effects of combination treatment with anti-inflammatory and neuroprotective agents in experimental autoimmune encephalomyelitis. J Neuroimmunol 219, 64-74 (2010).
  23. Ziehn, M.O., Avedisian, A.A., Tiwari-Woodruff, S. & Voskuhl, R.R. Hippocampal CA1 atrophy and synaptic loss during experimental autoimmune encephalomyelitis, EAE. Lab Invest 90, 774-786 (2010).
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  42. Palaszynski, K.M., Loo, K.K., Ashouri, J.F., Liu, H. & Voskuhl, R.R. Androgens are protective in experimental autoimmune encephalomyelitis: implications for multiple sclerosis. J Neuroimmunol 146, 144-152 (2004).
  43. Soldan, S.S., Alvarez Retuerto, A.I., Sicotte, N.L. & Voskuhl, R.R. Dysregulation of IL-10 and IL-12p40 in secondary progressive multiple sclerosis. J Neuroimmunol 146, 209-215 (2004).
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  46. Soldan, S.S., Retuerto, A.I., Sicotte, N.L. & Voskuhl, R.R. Immune modulation in multiple sclerosis patients treated with the pregnancy hormone estriol. J Immunol 171, 6267-6274 (2003).
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  49. Voskuhl, R.R., et al. Experimental autoimmune encephalomyelitis relapses are reduced in heterozygous golli MBP knockout mice. J Neuroimmunol 139, 44-50 (2003).
  50. Sicotte, N.L., et al. Treatment of multiple sclerosis with the pregnancy hormone estriol. Ann Neurol 52, 421-428 (2002).
  51. Voskuhl, R.R. Gender issues and multiple sclerosis. Curr Neurol Neurosci Rep 2, 277-286 (2002).

Director

Faculty

Researchers

Staff Physicians

Collaborators

  • Arthur Arnold, Ph.D. Arthur Arnold, Ph.D.
  • Robert Elashoff, Ph.D. Robert Elashoff, Ph.D.
  • Thomas O'Dell, Ph.D. Thomas O'Dell, Ph.D.
  • Michael Sofroniew, M.D., Ph.D.