| 1. Detection of autoantibodies that bind to endothelial cells in serum from people with demyelinating diseases |
| W. James Waldman, PhD, The Ohio State University |
| Approved: | 7/21/2011 |
| Status: | Study in Progress |
| Updated: | 9/29/2011 |
| Samples: | Serum
36 cases (10 RRMS 2 timepoints each, 10 SPMS, 4 ADEM, 4 NMO, 4 ON, 4 TM) and 10 controls |
| Funded by: | NIH/NINDS |
| Results: | Pending |
| Description: |
| Dr. Waldman and his team have discovered the presence of autoantibodies that bind to endothelial cells (the cells that line the inner surface of blood vessels) in the blood of patients with several diseases, including Susac's syndrome (SS). Their experiences with SS have led them to hypothesize that endothelial-reactive autoantibodies may also contribute to the disease process in MS, as well as other disorders such as TM, NMO, ADEM and ON, possibly by disruption of the blood-brain barrier. They plan to apply their sensitive antibody-detection methods to serum samples from our repository to determine whether these antibodies are indeed present. |
| |
| 2. The ability of anti-glucose antibodies to monitor MS disease activity and treatment efficacy |
| Nir Dotan, PhD, Glycominds Ltd. |
| Approved: | 5/20/2011 |
| Status: | Study in Progress |
| Updated: | 6/7/2011 |
| Samples: | Serum
271 cases (MS, 2 timepoints each) |
| Funded by: | Glycominds |
| Results: | Pending |
| Description: |
| The Glycominds team has developed an MS diagnostic assay based on anti-glucose antibodies. They are now interested in learning whether this assay could potentially also be used to monitor disease activity and severity, as well as whether changes in antibody levels reflect treatment efficacy. |
| |
| 3. Investigation of familial MS through genome sequencing and functional protein screening |
| May Han, MD, Stanford |
| Approved: | 5/20/2011 |
| Status: | Study in Progress |
| Updated: | 6/7/2011 |
| Samples: | DNA and serum
14 cases (MS and TM) and 7 controls |
| Funded by: | Internal funding |
| Results: | Pending |
| Description: |
| Some studies indicate that familial MS may take a more severe course than non-familial MS, and therefore different mechanisms may underlie familial MS and sporadic MS. Dr. Han's team plans to sequence the genome in familial MS and also screen samples on the functional level by using protein arrays. By comparing both genomic data and protein array data, they hope to find potential genetic markers and/or promising pathogenic proteins playing roles in familial MS. |
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| 4. Whole-genome screening of NMO samples |
| Joyce Tung, 23andMe |
| Approved: | 3/22/2011 |
| Status: | Study Completed |
| Updated: | 6/7/2011 |
| Samples: | DNA
115 cases (NMO) |
| Funded by: | Guthy-Jackson Charitable Foundation |
| Results: | Pending |
| Description: |
| Scientists at 23andMe will be screening NMO samples from the repository using a GWAS (genome wide association study) approach. The data generated may help to identify genetic variants that are more common in people who have NMO than in people who do not. |
| |
| 5. Analysis of repository data for relapse treatment trends |
| Heidi Mace, Questcor |
| Approved: | 3/22/2011 |
| Status: | MTA/DTA Signed |
| Updated: | 6/7/2011 |
| Samples: | Data
Not Applicable |
| Funded by: | Questcor |
| Results: | Pending |
| Description: |
| Questcor manufactures a drug called Acthar (native ACTH gel) which is a steroidogenic hormone but may also have other effects relevant to MS. Scientists at this company are interested in understanding the efficacy of relapse treatment in patients with relapsing remitting MS, beginning with basic data analysis to understand general trends. |
| |
| 6. Generation of interactive maps using repository data |
| Alan Yelsey, Knowledge Visualization Systems |
| Approved: | 3/22/2011 |
| Status: | Study in Progress |
| Updated: | 6/7/2011 |
| Samples: | Data
Not Applicable |
| Funded by: | KVS |
| Results: | Pending |
| Description: |
| Data visualization experts at KVS, in partnership with Accelerated Cure Project, will produce highly sophisticated systemic maps based upon ACP's repository data and other sources of knowledge about MS. The team's goal is to provide interactive maps of the data and knowledge associated with MS and create a unique interactive disease framework that produces new insights into MS. |
| |
| 7. Development of a PML risk prediction method using JCV antibodies |
| Peter Calabresi, MD, Johns Hopkins University |
| Approved: | 1/21/2011 |
| Status: | Study in Progress |
| Updated: | 6/7/2011 |
| Samples: | Serum
1 case (MS) to date |
| Funded by: | Biogen IDEC |
| Results: | Pending |
| Description: |
| Dr. Calabresi is collaborating with Dr. Susan Goelz at Biogen Idec to test for JC virus antibodies in banked sera from MS patients who have been treated with natalizumab and subsequently developed PML. This effort will contribute to methods for predicting risk of developing PML. |
| |
| 8. Whole blood gene expression profiling of samples from secondary progressive MS subjects |
| Jadwiga Bienkowska, Biogen Idec |
| Approved: | 1/21/2011 |
| Status: | Study in Progress |
| Updated: | 6/7/2011 |
| Samples: | PaxGene
214 cases (MS) and 30 controls |
| Funded by: | Biogen IDEC |
| Results: | Pending |
| Description: |
| The goal of this research proposal is to investigate the whole blood gene expression profiles of MS patients and specifically Secondary Progressive MS (SPMS) patients to better understand the molecular features of SPMS versus Relapsing-Remitting MS (RRMS). We believe that a better understanding of the involvement of the immune system in SPMS could lead to new therapies and improve lives of MS patients. |
| |
| 9. Association of CD24 gene variants with MS |
| Yang Liu, MD, University of Michigan |
| Approved: | 1/21/2011 |
| Status: | Study in Progress |
| Updated: | 6/7/2011 |
| Samples: | DNA
500 cases (MS) |
| Funded by: | -- |
| Results: | Pending |
| Description: |
| Dr. Liu and his colleagues are validating previous results in mouse models and human samples suggesting that variants in the CD24 gene may affect the risk of MS. |
| |
| 10. Measurement of neutrophil elastase in NMO samples |
| Marios Papadopoulos, MD FRCS(SN), St. George's, University of London |
| Approved: | 1/21/2011 |
| Status: | Done |
| Updated: | 6/7/2011 |
| Samples: | Plasma
55 cases (20 MS and 35 NMO) |
| Funded by: | Guthy-Jackson Charitable Foundation |
| Results: | Received |
| Description: |
| Immune cells called neutrophils have been identified in NMO lesions but are scarce in lesions of other demyelinating diseases such as MS and ADEM. These infiltrating neutrophils secrete elastase, which damages the brain. This study aims to evaluate whether neutrophil elastase concentration and activity are elevated in NMO patients during an acute attack, but not in NMO patients in remission or in MS patients. |
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| 11. Testing MS and control samples for exposure to Mycobacterium avium |
| Michael Warmoth, MD, Spectrum Health |
| Approved: | 12/3/2010 |
| Status: | Study in Progress |
| Updated: | 5/17/2011 |
| Samples: | Serum
30 cases (MS) and 20 controls |
| Funded by: | Internal funding |
| Results: | Pending |
| Description: |
| Drs. Warmoth and Collins are testing a hypothesis that the infectious organism Mycobacterium avium could be a trigger of MS. In this pilot study, they will test serum samples from MS and control subjects for evidence of infection with this bacteria. |
| |
| 12. Characterization of the pathogenic NMO-IgG and the B cell populations producing NMO-IgG |
| May Han, MD, Stanford |
| Approved: | 11/23/2010 |
| Status: | Study in Progress |
| Updated: | 5/17/2011 |
| Samples: | DNA, RNA, serum, PBMCs
40 cases (30 NMO and 10 MS) |
| Funded by: | Guthy-Jackson Charitable Foundation |
| Results: | Pending |
| Description: |
| NMO-IgG is an antibody against aquaporin-4 that has been found in the serum of people with neuromyelitis optica (NMO). It is thought to contribute directly to the disease but how and why it is produced by B cells is unknown. Dr. Han's team will use DNA, RNA, serum, and cell samples to explore this question. Results of this research could potentially help lead to treatments that target these antibodies and/or B cells. |
| |
| 13. Determine role of prion protein in patients with PPMS |
| Olaf Stuve, MD, PhD, University of Texas Southwestern |
| Approved: | 10/20/2010 |
| Status: | Done |
| Updated: | 5/17/2011 |
| Samples: | DNA
69 cases (MS) |
| Funded by: | Partly covered by a Merit Review Grant to Dr. Stuve by the Department of Veterans Affairs. |
| Results: | No significant differences were found in the frequencies of Prnp129 genotypes in PPMS subjects compared with controls. "No association between genetic polymorphism at codon 129 of the prion protein gene and primary progressive multiple sclerosis." Arch Neurol, February 2011. |
| Description: |
| Around 10% of people with MS have the primary progressive form of the disease, which can have a severe course and is not affected by any of the current MS disease-modifying therapies. Mutations in a gene called PrP (prion protein) have been found to increase the severity of other neurological diseases such as Alzheimer's disease. A team at UTSW will analyze samples from subjects with PPMS for the presence of a PrP mutation that has been associated with severity in another neurodegenerative disease. |
| |
| 14. Measurement of Intracellular mRNA levels of MSRV envelope protein in PBMCs |
| Francois Curtin, MD, GeNeuro SA |
| Approved: | 10/19/2010 |
| Status: | Study in Progress |
| Updated: | 1/6/2011 |
| Samples: | PBMCs
10 cases (MS), 10 controls |
| Funded by: | Internal funding |
| Results: | Pending |
| Description: |
| GeNeuro SA is a Swiss startup company developing an innovative disease modifying therapy for the cure of Multiple Sclerosis (MS). To this end, the company has generated a monoclonal antibody targeting the Multiple Sclerosis Related Retrovirus (MSRV) which GeNeuro considers to be a central factor of the disease. GeNeuro will use samples from the ACP Repository to validate previous data on the frequency of MSRV and to investigate its presence in people with different forms of MS and in different geographic locations. |
| |
| 15. Exploration of trauma as an environmental factor that might trigger onset of MS. |
| Carole Lunny, MHS, Athabasca University |
| Approved: | 7/22/2010 |
| Status: | Study in Progress |
| Updated: | 1/6/2011 |
| Samples: | Data
Not Applicable |
| Funded by: | Internal funding |
| Results: | Pending |
| Description: |
| Whether physical trauma plays a role in causing MS has been debated since the earliest descriptions of the illness, and the role of trauma in the development of MS has been the subject of many studies over the last 50 years. Investigators from Athabasca University propose to analyze our repository database and include this information in a meta-analysis currently underway to further contribute to answering the question of whether trauma is associated with onset of MS. |
| |
| 16. High-throughput screening study to identify peptoid ligands to anti-AQP4 |
| Roberto Baccala, PhD, The Scripps Research Institute |
| Approved: | 5/18/2010 |
| Status: | Study in Progress |
| Updated: | 1/6/2011 |
| Samples: | Serum
91 cases (10 MS, 81 NMO) and 20 controls |
| Funded by: | Guthy-Jackson Charitable Foundation |
| Results: | Pending |
| Description: |
| Antibodies to the protein aquaporin-4 are commonly found in people diagnosed with NMO, and are thought to cause or contribute to the disease. This study will use a high-throughput screening system to identify molecules that can bind to or block anti-AQP4 autoantibodies. The results of this research could help with diagnosis, development of animal models, and, more importantly, the treatment of NMO. |
| |
| 17. Testing the hypothesis that unnatural amino acid misincorporated into myelin basic protein makes it immunogenic |
| Manish J. Butte, MD, PhD, Stanford |
| Approved: | 5/18/2010 |
| Status: | Study in Progress |
| Updated: | 1/6/2011 |
| Samples: | Whole blood
11 cases (MS), 8 controls |
| Funded by: | CTSA-sponsored project called SPARK. |
| Results: | Pending |
| Description: |
| Dr. Butte is conducting a pilot study to test the hypothesis that the incorrect incorporation of an amino acid found in certain foods into myelin basic protein (MBP) changes the structure of MBP, making it subject to immune attack. The experiment will test how T cells from the blood of people with MS will react when exposed to this altered form of MBP. |
| |
| 18. Effect of treatment intervention in TM and NMO on disease outcome. |
| Benjamin M. Greenberg, MD, MHS, University of Texas Southwestern |
| Approved: | 5/18/2010 |
| Status: | Study in Progress |
| Updated: | 6/4/2010 |
| Samples: | Data
Not Applicable |
| Funded by: | -- |
| Results: | Pending |
| Description: |
| A team from UT Southwestern is conducting research to analyze the impact of therapeutic intervention in TM and NMO patients. In particular, they would like to learn whether timely treatment administration could help prevent disability. They will be analyzing data from our repository as part of their investigation. |
| |
| 19. Exploration of EBV immune response and interactions with other MS risk factors |
| Alberto Ascherio, MD, PhD, Harvard School of Public Health |
| Approved: | 5/6/2010 |
| Status: | Study in Progress |
| Updated: | 6/7/2011 |
| Samples: | DNA, serum, whole blood
80 cases (MS) and 80 controls (EBV study), 854 cases (654 MS, 78 NMO, 122 TM) and 215 controls (DNA), 1550 cases (1238 MS, 100 NMO, 11 ON, 133 TM, 22 ADEM, 46 CIS) and 464 controls (serum) |
| Funded by: | ACP |
| Results: | Pending |
| Description: |
| Epstein-Barr virus (EBV) and infectious mononucleosis have both been associated with MS in numerous studies, but the mechanism by which EBV affects MS risk is not yet understood. Dr. Ascherio and his team are analyzing repository samples and data from a number of standpoints to further explore the EBV/MS connection. For instance, they are determining whether genetic and environmental factors associated with MS risk correlate with antibody levels to EBV. |
| |
| 20. Analyzing presence of phosphorylated neurofilament heavy chain |
| Helmut Butzkueven, MD, Howard Florey Institute |
| Approved: | 4/22/2010 |
| Status: | Study in Progress |
| Updated: | 10/20/2010 |
| Samples: | Serum
733 cases (MS) and 100 controls |
| Funded by: | Multiple Sclerosis Research Australia (MSRA) |
| Results: | Pending |
| Description: |
| Drs. Butzkueven and Gresle will be analyzing serum samples for the presence of phosphorylated neurofilament heavy chain (pNF-H), which is a possible marker of neurodegeneration in MS. Levels of pNF-H will be correlated both with disease severity indicators and with the metabolite data that has been generated by Dr. Gilles Guillemin's analysis of the same samples. |
| |
| 21. Use PCR based assay to look for isoforms of aquaporin-4 (AQP4) |
| Michael Levy, MD, PhD, Johns Hopkins University |
| Approved: | 3/19/2010 |
| Status: | Distribution Wrap Up |
| Updated: | 1/6/2011 |
| Samples: | RNA
21 cases (5 MS, 5 TM, 11 NMO) and 5 controls |
| Funded by: | Guthy-Jackson Charitable Foundation |
| Results: | Received |
| Description: |
| Antibodies that bind to the molecule aquaporin-4 (AQP4) are often found in the blood of people diagnosed with NMO. AQP4 is expressed in central nervous system cells called astrocytes, but it is expressed in other cells as well. Dr. Levy's project involves measuring levels of a certain form of AQP4 in white blood cells to see whether these levels change during relapse and remission. This research may lead to development of a biomarker of NMO disease activity. |
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| 22. Determine the affinity and efficacy of NMO-IgG binding to the M1 and M23 isoforms of AQP4 |
| Alan S. Verkman, MD, PhD, University of California San Francisco |
| Approved: | 3/18/2010 |
| Status: | Study in Progress |
| Updated: | 1/6/2011 |
| Samples: | Serum
36 cases (24 NMO, 12 MS) |
| Funded by: | Guthy-Jackson Charitable Foundation |
| Results: | Pending |
| Description: |
| In this collaborative project, researchers from UC San Francisco and UT Southwestern will be examining how strongly IgG antibodies found in serum of NMO subjects bind to the different forms of aquaporin-4. The goal of the research is to correlate binding characteristics of NMO-IgG with various parameters, including age, sex, age of onset, years of disease, disease severity, and treatment status. The information from these studies may provide a novel serum diagnostic test of disease severity and response to therapy. |
| |
| 23. Analysis of visfatin levels in plasma samples |
| Ramesh C. Nayak, PhD, MSDx, LLC |
| Approved: | 2/8/2010 |
| Status: | Study in Progress |
| Updated: | 1/6/2011 |
| Samples: | Plasma
83 cases (50 MS, 12 Tysabri x2, 14 Copaxone x2, 7 Avonex x2), 10 controls |
| Funded by: | MSDx |
| Results: | Pending |
| Description: |
| Researchers at MSDx have found that levels of a protein called visfatin are elevated in people with MS. They are using plasma samples from the Accelerated Cure Project to further explore and validate this finding. Visfatin is associated with obesity and metabolism, but also promotes inflammation, which may form the basis of its potential connection with MS. |
| |
| 24. Application of interactive classification and clustering techniques to the repository database |
| Marie desJardins, University of Maryland |
| Approved: | 1/26/2010 |
| Status: | Study in Progress |
| Updated: | 2/26/2010 |
| Samples: | Data
Not Applicable |
| Funded by: | None |
| Results: | Pending |
| Description: |
| A team at UMBC will be analyzing our repository database using machine learning techniques to find patterns in the data that may reveal disease subtypes or factors that may cause or be correlated with a demyelinating disease. Machine learning involves programming computers so that they can automatically recognize patterns or make decisions based on input they are given. The breadth and diversity of data in our database makes it a good candidate for analysis by these types of techniques. |
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| 25. Identify biomarkers that can diagnose MS and distinguish its forms |
| Sally K. Nelson, PhD, SomaLogic |
| Approved: | 11/24/2009 |
| Status: | Study in Progress |
| Updated: | 1/6/2011 |
| Samples: | Serum
100 cases (50 MS, 3 NMO, 4 ON, 38 TM, 5 ADEM) and 50 controls |
| Funded by: | SomaLogic, Inc. |
| Results: | Pending |
| Description: |
| The company SomaLogic has developed a novel technology platform for finding protein biomarkers in plasma and serum samples. Samples from our repository will be analyzed with this platform to identify biomarkers that can diagnose MS and distinguish its different forms, measure a person's response to treatment, and provide insight into progression and severity of the disease. |
| |
| 26. Find gene expression patterns by analyzing miRNA |
| Eric M. Eastman, PhD, Diogenix, Inc. |
| Approved: | 11/20/2009 |
| Status: | Study in Progress |
| Updated: | 1/6/2011 |
| Samples: | Serum
225 cases (MS, NMO, TM, ADEM, ON) and 114 controls |
| Funded by: | Diogenix |
| Results: | Pending |
| Description: |
| The production of proteins in cells is affected by many factors, one of which is the presence of a type of molecule called micro RNA (miRNA). miRNAs are small RNA molecules that affect the stability and translation of messenger RNA (mRNA) molecules. Diogenix is including miRNA analysis in their ongoing efforts to find gene expression patterns that can diagnose and classify MS. |
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| 27. Determine if early life exposure to siblings impacts the risk of MS |
| Benjamin M. Greenberg, MD, MHS, University of Texas Southwestern |
| Approved: | 10/7/2009 |
| Status: | Study in Progress |
| Updated: | 2/3/2010 |
| Samples: | Data
Not Applicable |
| Funded by: | -- |
| Results: | Pending |
| Description: |
| This study will analyze the ACP database to determine if early life exposure to siblings impacts the risk of developing MS. Some studies have found a correlation between early life exposure to infants and decreased risk of MS which may relate to the hygiene hypothesis of autoimmune diseases. According to the theory, having exposures to viral infections during development reduces the risk of an autoimmune condition such as MS. Determining if this is true in a large scale survey could significantly impact our understanding of the triggers for these diseases. |
| |
| 28. Establish biomarker profiles for patients with Multiple Sclerosis |
| Thomas Misko, PhD, Pfizer Inflammation Research |
| Approved: | 9/22/2009 |
| Status: | Done |
| Updated: | 2/3/2010 |
| Samples: | EDTA plasma
50 cases (MS-RRMS) and 50 cases (MS-SPMS) |
| Funded by: | Pfizer |
| Results: | Received |
| Description: |
| Scientists at Pfizer are analyzing samples from our repository to gain a better understanding of disease activity and progression in MS. Results from their analysis may help in the development of new therapies as well as lead to new methods for monitoring the clinical course of MS. |
| |
| 29. Analysis of immune-related biomarkers |
| Philip DeJager, MD, PhD, Brigham & Women's Hospital |
| Approved: | 9/16/2009 |
| Status: | Study in Progress |
| Updated: | 1/6/2011 |
| Samples: | Serum
193 cases (147 MS, 24 TM, 22 CIS) and 100 controls |
| Funded by: | -- |
| Results: | Pending |
| Description: |
| Researchers at the Partners MS Center have been working to find biomarkers that can diagnose MS, predict clinical course, and gauge risk of MS. Samples from the Accelerated Cure Project repository will be used to validate a set of 22 biomarkers involved in inflammation that could aid in establishing a diagnosis of MS. |
| |
| 30. Development of a diagnostic product for MS |
| Ramesh C. Nayak, PhD, MSDx, LLC |
| Approved: | 9/1/2009 |
| Status: | Study in Progress |
| Updated: | 2/3/2010 |
| Samples: | PBMCs
110 cases (75 MS, 15 CIS, 10 NMO, 10 ADEM) and 10 controls |
| Funded by: | Company MSDx, LLC |
| Results: | Pending |
| Description: |
| MSDx is a start-up company that is developing a new technique for diagnosing and monitoring MS. This technique analyzes the contents of blood cells called phagocytes for evidence of brain tissue debris. MSDx plans to develop this technique so that it can be used to help diagnose MS, monitor disease activity to prevent relapse, and monitor drug effects to distinguish responders and non-responders. Our blood samples will be used to further refine this technique. |
| |
| 31. Determining information on DNA methylation in the SHP-1 gene |
| Paul Massa, PhD, SUNY Upstate Medical University |
| Approved: | 7/24/2009 |
| Status: | Study in Progress |
| Updated: | 12/16/2009 |
| Samples: | DNA
50 cases (MS) and 200 controls |
| Funded by: | NIH |
| Results: | Pending |
| Description: |
| A regulatory protein called SHP-1 can control the inflammatory activities of immune cells. People with MS have been found to be deficient in SHP-1 compared with controls, and this deficiency has been shown to contribute to the increased expression of pro-inflammatory genes. This research study will explore whether a certain type of modification (called methylation) to the SHP-1 gene is responsible for decreased SHP-1 levels in people with MS. We are providing DNA samples to support this study. |
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| 32. Development of a test for in-vitro diagnosis of MS |
| Stefan Mullner, PhD, Protagen AG |
| Approved: | 5/20/2009 |
| Status: | Study in Progress |
| Updated: | 1/6/2011 |
| Samples: | Serum
10 cases (1st phase of 3 phase study) 20 cases (MS) and 20 controls (2nd phase of 3 phase study) 15 controls (2a phase of 3 phase study) |
| Funded by: | Protagen AG |
| Results: | Pending |
| Description: |
| During our lifespan, everyone produces antibodies directed against human antigens (proteins). Usually, these so-called autoantibodies do not cause disease. However, in so-called autoimmune diseases the autoantibodies cause clinical symptoms, i.e., a disease. Protagen is developing a test to diagnose MS based on the patterns of autoantibodies found in serum samples. Ideally this test will also distinguish among the clinical subtypes CIS, RRMS and SPMS. |
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| 33. Molecular Studies of Neuromyelitis Optica in Mouse Models of Aquaporin-4 Autoimmunity |
| Roberto Baccala, PhD, The Scripps Research Institute |
| Approved: | 5/20/2009 |
| Status: | Study in Progress |
| Updated: | 6/25/2009 |
| Samples: | Serum
5 cases (NMO) and 5 controls |
| Funded by: | Guthy-Jackson Charitable Foundation |
| Results: | Pending |
| Description: |
| Researchers at The Scripps Research Institute are developing a mouse model of autoimmunity to AQP4, which can be used to better understand the human disease neuromyelitis optica (NMO) and develop novel therapies for it. Serum samples from subjects with NMO and controls will be used to develop and validate this mouse model. |
| |
| 34. Determining whether NMO-IgG affects important functions of AQP4 |
| Alan S. Verkman, MD, PhD, University of California San Francisco |
| Approved: | 3/17/2009 |
| Status: | Study in Progress |
| Updated: | 4/22/2009 |
| Samples: | Serum
10 cases (NMO) and 5 controls |
| Funded by: | Guthy-Jackson Charitable Foundation |
| Results: | Pending |
| Description: |
| An antibody to a protein called aquaporin-4 (AQP4) has been found in a majority of people with neuromyelitis optica (NMO). Discovery of this antibody, NMO-IgG, has improved the diagnosis of NMO, provided new insights into how the disease develops, and suggested new therapeutic strategies. A research team at UCSF will investigate several key aspects of the roles of AQP4 and NMO-IgG at the molecular level and the astrocyte cell level. They will determine whether the antibody to AQP4 affects important functions of AQP4 in cells, such as allowing water through cell membranes, assembling into structured arrays, and facilitating cell movement. |
| |
| 35. Development of an FDA-approved MS diagnostic test |
| Douglas Bigwood, PhD, Diogenix, Inc. |
| Approved: | 1/6/2009 |
| Status: | Study in Progress |
| Updated: | 6/25/2009 |
| Samples: | PaxGene
pending |
| Funded by: | Diogenix |
| Results: | Pending |
| Description: |
| This is an extension of the study "Human gene expression for developing an MS diagnostic signature": Samples are being analyzed to confirm blood-based gene expression patterns that discriminate between MS and non-MS subjects and could form the basis for a type of diagnostic test. A test capable of providing an early and definitive diagnosis of MS and differentiating MS subtypes would not only facilitate earlier delivery of proper therapy but would help alleviate undue anxiety for patients and their families. |
| |
| 36. Neurodegeneration in people with SPMS |
| Julius Birnbaum, MD, MHS, Johns Hopkins University |
| Approved: | 12/31/2008 |
| Status: | Study Completed |
| Updated: | 4/22/2009 |
| Samples: | Serum
619 (MS) and all available controls |
| Funded by: | NIH K12 grant |
| Results: | Pending |
| Description: |
| Recent studies of brain tissue have demonstrated that the brains of people with secondary progressive MS (SPMS) may feature subtle but diffuse inflammation. Other experiments analyzing brains of patients with SPMS have shown signs of decreased oxygen, otherwise termed "hypoxic" injury. Dr. Birnbaum and his team will investigate serum samples from people with MS and controls to see whether antibodies associated with hypoxic injury are present, along with typical risk factors of blood vessel injury, to explore the possibility that injury to blood vessels may trigger neurodegeneration in people with SPMS. |
| |
| 37. Creation of in vitro diagnostic blood test for MS |
| Thomas M. Aune, PhD, Vanderbilt |
| Approved: | 9/17/2008 |
| Status: | Done |
| Updated: | 4/1/2009 |
| Samples: | RNA
111 cases (80 MS, 20 TM, 6 NMO, 1 ON, 4 ADEM) |
| Funded by: | NIH STTR grant |
| Results: | Results of this study indicated that gene expression signatures in blood can accurately support or exclude a diagnosis of MS. "Gene-expression signatures: biomarkers toward diagnosing multiple sclerosis." Genes and Immunity, September 22, 2011. |
| Description: |
| Multiple sclerosis is a disease that is difficult to diagnose. Diagnosis in early stages of disease would be facilitated by an accurate blood test and this is key to timely institution of definitive therapies that reduce the rate of disease progression and onset of disability. The goal of our research is to develop an accurate blood test for multiple sclerosis and evaluate its performance in different subject populations. A simple in vitro diagnostic blood test for MS could decrease the time between the time of onset of clinical symptoms of MS and a definitive diagnosis of MS. It could also aid in excluding someone from having MS. |
| |
| 38. The ability of anti-glucose antibodies to diagnose and stratify MS patients |
| Nir Dotan, PhD, Glycominds Ltd. |
| Approved: | 7/15/2008 |
| Status: | Done |
| Updated: | 4/1/2009 |
| Samples: | Serum
868 cases (743 MS, 71 TM, 13 NMO, 4 ON, 6 ADEM, 31 CIS), 140 unrelated controls and 251 related controls |
| Funded by: | Glycominds |
| Results: | Presented at the AAN 2010 Annual Meeting: Antibodies (gMS[Dx Test) Differentiate Newly Diagnosed Relapsing Remitting Multiple Sclerosis Patients from Other Inflammatory Demyelinating Disease Patients within One Year from Diagnosis |
| Description: |
| Glycominds used samples from our repository to validate an assay based on anti-glucose antibodies. This assay is being developed for use in diagnosing MS and predicting different aspects of the disease. |
| |
| 39. Regression analysis of genetic and environmental MS risk factors |
| Xuyang Tang, St. John's University |
| Approved: | 7/8/2008 |
| Status: | Done |
| Updated: | 7/15/2008 |
| Samples: | Data
Not Applicable |
| Funded by: | St. John's University |
| Results: | Received |
| Description: |
| This research project analyzed data from our repository database concerning different genetic and environmental factors from MS and non-MS subjects, and explored what this information could reveal about risk factors for MS. |
| |
| 40. The role of tryptophan metabolism in MS |
| Gilles J. Guillemin, PhD, St. Vincent's |
| Approved: | 6/20/2008 |
| Status: | Data Analysis Completed |
| Updated: | 4/1/2009 |
| Samples: | Serum
733 cases (MS) and 100 controls |
| Funded by: | Multiple Sclerosis Research Australia (MSRA) |
| Results: | Received |
| Description: |
| Researchers at St. Vincent's propose to demonstrate that tryptophan metabolism plays an important role in multiple sclerosis (MS). This project may open a new and important therapeutic door for MS using different specific inhibitors already available from drug companies for other brain diseases. |
| |
| 41. An international collaboration to perform whole-genome screens on MS samples |
| Philip DeJager, MD, PhD, Wellcome Trust Project |
| Approved: | 5/22/2008 |
| Status: | Done |
| Updated: | 6/7/2011 |
| Samples: | DNA
574 cases (MS) |
| Funded by: | Wellcome Trust |
| Results: | This genome-wide association study replicated almost all of the previously suggested associations and identified at least a further 29 novel loci associated with MS susceptibility. Genes involved in the immune system figured significantly in the list of results. Further progress was made on understanding the contribution of HLA-DRB1 to MS risk. "Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis." Nature, August 11, 2011. |
| Description: |
| The Wellcome Trust is funding an international collaboration to perform whole-genome screens on several thousand MS samples. Accelerated Cure Project has contributed DNA samples to this effort, which aims to screen MS samples for genes that affect the risk of MS. The whole-genome screens could allow a better understanding of the causes of MS. |
| |
| 42. Building ontologies to structure patient registry data |
| Alan Ruttenberg, Science Commons |
| Approved: | 5/15/2008 |
| Status: | Product Delivered |
| Updated: | 8/27/2008 |
| Samples: | Data
Not Applicable |
| Funded by: | |
| Results: | Pending |
| Description: |
| Science Commons will be applying and building ontologies in order to structure patient registry data for effective query and analysis. By making primary data structured in a clear and consistent way and enabling computation researchers easy access we hope to make it easier for computational scientists to apply new methods to mine this data. |
| |
| 43. Gene alleles that affect protein glycosylation |
| Michael Demetriou, MD, University of California Irvine |
| Approved: | 4/4/2008 |
| Status: | Done |
| Updated: | 6/7/2011 |
| Samples: | DNA
871 cases (746 MS, 13 NMO, 4 ON, 69 TM, 8 ADEM, 31 CIS) and 18 unrelated controls |
| Funded by: | National Multiple Sclerosis Society |
| Results: | Results from this study implicate genetic and environmental factors that affect protein glycosylation as playing a role in MS. "Genetics and the environment converge to dysregulate N-glycosylation in multiple sclerosis." Nat Commun. 2011. |
| Description: |
| Researchers at UCI have found that genetic deficiency in a pathway that controls the addition of specific sugars to proteins leads to immune hyperactivity and spontaneous development of an MS-like disease in mice. They have identified two genetic defects in humans that alter the same glycosylation pathway. Repository samples will be used in conjunction with other samples to identify additional genetic changes that lead to the same defect in protein glycosylation and show that these can also be treated by metabolic therapy. |
| |
| 44. Investigating the involvement of Vitamin D related genes and MS |
| Alberto Ascherio, MD, PhD, Harvard School of Public Health |
| Approved: | 3/10/2008 |
| Status: | Done |
| Updated: | 6/7/2011 |
| Samples: | DNA
650 cases (MS) and 243 controls |
| Funded by: | NIH (Grant: R01) |
| Results: | Received |
| Description: |
| Samples will be used to explore the role of Vitamin D as it relates to MS. Researchers will be considering genes involved in Vitamin D metabolism and investigating how these might be related to an individual's risk of MS. By considering potential genetic factors, researchers may be able to determine if certain individuals would benefit even more from increased Vitamin D and potentially further elucidate what the underlying biological effect of Vitamin D may be as it relates to MS. |
| |
| 45. Validation of genetic determinants of disease course in MS |
| Philip DeJager, MD, PhD, Broad Institute |
| Approved: | 2/22/2008 |
| Status: | Done |
| Updated: | 6/25/2009 |
| Samples: | DNA
735 cases (640 MS, 11 NMO, 3 ON, 54 TM, 4 ADEM, 23 CIS) and 242 controls |
| Funded by: | Accelerated Cure Project |
| Results: | Several genetic associations have been discovered or confirmed. "Genetic variation in the IL7RA/IL7 pathway increases multiple sclerosis susceptibility." Human Genetics, January 30 2010 (Epub). "Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci." Nature Genetics, July 2009. "IL12A, MPHOSPH9/CDK2AP1 and RGS1 are novel multiple sclerosis susceptibility loci." Genes and Immunity, June 17 2010 (Epub). "Comprehensive follow-up of the first genome-wide association study of multiple sclerosis identifies KIF21B and TMEM39A as susceptibility loci." Human Molecular Genetics, December 23 2009 (Epub). |
| Description: |
| Repository samples will be used to validate the results of a previous genome scan conducted on 1000 MS subjects. The scan was done to discover genetic variants that affect the course of disease in patients with MS. The genetic variants may help explain why MS progresses differently in its patients. Samples are also being used in projects performed by the International MS Genetics Consortium to explore and confirm genetic associations with MS. |
| |
| 46. Genetic and immunogenic analysis of AQP4 in neuromyelitis optica |
| Brian Weinshenker, MD, Mayo Clinic |
| Approved: | 11/9/2007 |
| Status: | Done |
| Updated: | 4/1/2009 |
| Samples: | DNA
5 cases (NMO) |
| Funded by: | Multiple Sclerosis International Federation, Mayo Foundation |
| Results: | "Genetic analysis of aquaporin-4 in neuromyelitis optica." Neurology, September 20, 2011. "HLA DRB1*1501 tagging rs3135388 polymorphism is not associated with neuromyelitis optica." Multiple Sclerosis, June 30 2010 (Epub). Presentation at AAN 04/09: "The MS-associated gene HLA DRB1*1501 was not found to be a risk factor for NMO" Presentation at AAN 2009: "Two Different Arg19 Mutations in the N-terminus of Aquaporin-4 Suggest a Molecular Mechanism for Susceptibility to Neuromyelitis Optica" Presentation at ECTRIMS 2009: "Genetic analysis of neuromyelitis optica: two different Arg19 mutations in the N-terminus of aquaporin-4 suggest a molecular mechanism for susceptibility to NMO" |
| Description: |
| Researchers at Mayo Clinic have discovered that a large number of patients with neuromyelitis optica, also known as optico-spinal MS, have antibodies in the blood against a protein in the nervous system called aquaporin-4. The Mayo clinic researchers are studying the gene that produces this protein. They will use repository samples to find out whether and how mutations in this gene are linked with development of the disease, which could determine prevention initiatives. Other genetic variants will also be examined for involvement in NMO. |
| |
| 47. Human gene expression for developing an MS diagnostic signature |
| Douglas Bigwood, PhD, Diogenix, Inc. |
| Approved: | 9/1/2007 |
| Status: | Done |
| Updated: | 6/4/2008 |
| Samples: | RNA
70 cases (60 MS and 10 TM) and 50 controls |
| Funded by: | Gene Logic Inc. |
| Results: | Received |
| Description: |
| Samples are being analyzed to confirm blood-based gene expression patterns that discriminate between MS and non-MS subjects and could form the basis for a type of diagnostic test. A test capable of providing an early and definitive diagnosis of MS and differentiating MS subtypes would not only facilitate earlier delivery of proper therapy but would help alleviate undue anxiety for patients and their families. |
| |
| 48. Variations in mitochondrial DNA |
| David K. Simon, MD, PhD, Beth Israel Deaconess Medical Center |
| Approved: | 7/25/2007 |
| Status: | Done |
| Updated: | 6/7/2011 |
| Samples: | DNA
382 cases (346 MS, 6 NMO, 2 ON, 19 TM, 1 ADEM, 8 CIS) and 31 controls |
| Funded by: | Canadian Pediatric Demyelinating Disease Initiative |
| Results: | Received |
| Description: |
| Mutations in mitochondrial DNA (mtDNA) have been associated with severe optic nerve injury in patients with a disorder known as Leber's Hereditary Optic Neuropathy (LHON), and the same mutations also have been identified in very rare MS patients, usually in association with severe optic nerve involvement. Numerous prior studies have examined the possibility that LHON-associated mtDNA mutations or other mtDNA variants might influence the risk of MS or clinical features of MS, but a definitive answer is lacking. As a result, researchers at Beth Israel Deaconess Medical Center are using samples to examine mtDNA variants hypothesized to play a role in the risk of MS. The results could help identify people who are at higher risk for MS and could also help advance our understanding of the causes and treatment of MS. |
| |
| 49. Identification of a host-pathogen interaction in people with MS |
| Viktor Stolc, PhD, NASA |
| Approved: | 3/22/2007 |
| Status: | Study Completed |
| Updated: | 4/1/2009 |
| Samples: | DNA and RNA
20 cases (MS) and 20 controls |
| Funded by: | NASA |
| Results: | Pending |
| Description: |
| Repository samples will be used in the largest screen for active pathogens (viruses, bacteria, and fungi) ever undertaken in subjects with MS. Additionally, the human gene expression levels of these subjects will be analyzed in order to identify a pattern of host-pathogen interactions that are present in people with MS. If a pattern is found, it could explain how MS is caused. |
| |
| 50. Variations in inflammatory genes |
| Bernadette Kalman, MD, SUNY Upstate Medical University |
| Approved: | 12/1/2006 |
| Status: | Done |
| Updated: | 5/27/2008 |
| Samples: | DNA
150 cases (MS) |
| Funded by: | National Multiple Sclerosis Society (Grants: RG3521A6/T and NMSS PP1334), Serono Inc. |
| Results: | Two sets of results from this study has been published identifying gene variants that appear to affect MS risk and severity. "Association of common mitochondrial DNA variants with multiple sclerosis and systemic lupus erythematosus." Clinical Immunolology, October 2008. "CCL genes in multiple sclerosis and systemic lupus erythematosus." Journal of Neuroimmunology, August 30 2008. |
| Description: |
| Researchers at the Syracuse VA Medical Center used our samples to explore gene variations in MS subjects and unaffected healthy individuals to determine how variations in inflammatory genes contribute to the development of MS. They also studied whether these genetic variations correlate with disease severity. Specific gene variants could explain why some MS patients develop more severe symptoms than others. |
| |
| 51. Antibodies to blood-brain barrier |
| Ben Barres, MD, PhD, Stanford |
| Approved: | 7/5/2006 |
| Status: | Data Analysis in Progress |
| Updated: | 10/16/2007 |
| Samples: | Serum
25 cases (MS) and 13 controls |
| Funded by: | Myelin Repair Foundation |
| Results: | Pending |
| Description: |
| Researchers at the Stanford School of Medicine are using samples collected during the pilot phase of the repository to assess the presence of antibodies that target the blood-brain barrier (BBB). Their research is focused on the role of the BBB in the progression of MS and whether the BBB is the target of an immune response which may lead to MS. If the BBB plays a significant role in MS, it may enable better treatments and possible cures to be discovered. |
| |
| 52. Investigation of myelin damage markers |
| David R. Colman, PhD, Montreal Neurological Institute |
| Approved: | 4/18/2006 |
| Status: | On Hold |
| Updated: | 5/22/2006 |
| Samples: | Serum
28 cases (MS) and 15 controls |
| Funded by: | Myelin Repair Foundation |
| Results: | Pending |
| Description: |
| Researchers at Montreal Neurological Institute (MNI) are using samples collected during the pilot phase of the repository to investigate a number of possible myelin damage markers that may be detectable in the serum of MS subjects. More knowledge of myelin damage markers could lead to more effective treatments. |
| |
| 53. Humoral response of MS patients to the Epstein-Barr virus |
| Judith A. James, MD, PhD, Oklahoma Medical Research Foundation |
| Approved: | 9/26/2005 |
| Status: | Done |
| Updated: | 12/29/2007 |
| Samples: | Serum
15 cases (MS) and 7 controls |
| Funded by: | Oklahoma Medical Research Foundation |
| Results: | A poster and findings were presented at the Federation of Clinical Immunology Societies (FOCIS) annual meeting in June 2006. Based on the samples from MS subjects and unaffected controls studied, it was reported that MS subjects did appear to have a unique response to the major nuclear antigen of EBV, EBNA-1 |
| Description: |
| A research team from Oklahoma Medical Research Foundation (OMRF) used samples collected during the pilot phase of the repository to study the relationship between the Epstein-Barr virus (EBV) and MS. Building upon their prior work studying EBV and systemic lupus erythematosus (SLE), the researchers focused on studying the response of MS subjects to EBV, based on the hypothesis that the immune system response of MS patients to EBV differs from that of non-affected individuals, while their responses to other common viruses (chickenpox, herpes simplex 1 and 2, etc.) are quite similar. Based on the samples from MS subjects and unaffected controls that they studied, they reported that MS subjects did appear to have a unique response to the major nuclear antigen of EBV, EBNA-1. With further research, this unique response could reveal EBV as a possible cause of MS. |
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