| 1. Validation of genetic determinants of disease course in MS |
| Philip DeJager, M.D., Ph.D. Broad Institute |
| Approved: | 2/22/2008 |
| Status: | Publication / IP Completed |
| 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: | Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci. |
| 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. |
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| 2. Molecular Studies of Neuromyelitis Optica in Mouse Models of Aquaporin-4 Autoimmunity |
| Roberto Baccala, Ph.D. 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. |
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| 3. Neurodegeneration in people with SPMS |
| Julius Birnbaum, M.D., M.H.S. Johns Hopkins University |
| Approved: | 12/31/2008 |
| Status: | Study in Progress |
| 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. |
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| 4. Determining whether NMO-IgG affects important functions of AQP4 |
| Alan S. Verkman, M.D., Ph.D. 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. |
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| 5. The ability of anti-glucose antibodies to diagnose and stratify MS patients |
| Nir Dotan, Ph.D. Glycominds Ltd. |
| Approved: | 7/15/2008 |
| Status: | Study in Progress |
| 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: | Pending |
| Description: |
| Glycominds proposes to use 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. |
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| 6. The role of tryptophan metabolism in MS |
| Gilles J. Guillemin, Ph.D. St. Vincent's |
| Approved: | 6/20/2008 |
| Status: | Data Analysis in Progress |
| Updated: | 4/1/2009 |
| Samples: | Serum
733 cases (MS) and 100 controls |
| Funded by: | Multiple Sclerosis Research Australia (MSRA) |
| Results: | Pending |
| 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. |
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| 7. Creation of in vitro diagnostic blood test for MS |
| Thomas M. Aune, Ph.D. Vanderbilt |
| Approved: | 9/17/2008 |
| Status: | Study in Progress |
| Updated: | 4/1/2009 |
| Samples: | RNA
111 cases (80 MS, 20 TM, 6 NMO, 1 ON, 4 ADEM) |
| Funded by: | NIH STTR grant |
| Results: | Pending |
| 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. |
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| 8. Genetic and immunogenic analysis of AQP4 in neuromyelitis optica |
| Brian Weinshenker, M.D. Mayo Clinic |
| Approved: | 11/9/2007 |
| Status: | Publication / IP in Progress |
| Updated: | 4/1/2009 |
| Samples: | DNA
5 cases (NMO) |
| Funded by: | Multiple Sclerosis International Federation, Mayo Foundation |
| Results: | Pending |
| 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. |
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| 9. Investigating the involvement of Vitamin D related genes and MS |
| Alberto Ascherio, M.D., Ph.D. Harvard School of Public Health |
| Approved: | 3/10/2008 |
| Status: | Data Analysis in Progress |
| Updated: | 4/1/2009 |
| Samples: | DNA
650 cases (MS) and 243 controls |
| Funded by: | NIH (Grant: R01) |
| Results: | Pending |
| 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. |
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| 10. Gene alleles that affect protein glycosylation |
| Michael Demetriou, M.D. University of California Irvine |
| Approved: | 4/4/2008 |
| Status: | Study in Progress |
| Updated: | 4/1/2009 |
| 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: | Pending |
| 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. |
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| 11. Identification of a host-pathogen interaction in people with MS |
| Viktor Stolc, Ph.D. NASA |
| Approved: | 3/22/2007 |
| Status: | Study in Progress |
| 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. |
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| 12. An international collaboration to perform whole-genome screens on MS samples |
| Philip DeJager, M.D., Ph.D. Wellcome Trust Project |
| Approved: | 5/22/2008 |
| Status: | Study in Progress |
| Updated: | 4/1/2009 |
| Samples: | DNA
574 cases (MS) |
| Funded by: | Wellcome Trust |
| Results: | Pending |
| 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. |
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| 13. 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. |
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| 14. 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: | Pending |
| 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. |
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| 15. Human gene expression for developing an MS diagnostic signature |
| Douglas Bigwood, Ph.D. Diogenix, Inc. |
| Approved: | 9/1/2007 |
| Status: | Data Analysis Completed |
| Updated: | 6/4/2008 |
| Samples: | RNA
70 cases (60 MS and 10 TM) and 50 controls |
| Funded by: | Gene Logic Inc. |
| Results: | Pending |
| 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. |
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| 16. Variations in inflammatory genes |
| Bernadette Kalman, M.D. 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: | One set of results from this study has been published identifying gene variants that appear to affect MS severity. |
| 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. |
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| 17. Variations in mitochondrial DNA |
| David K. Simon, M.D., Ph.D. Beth Israel Deaconess Medical Center |
| Approved: | 7/25/2007 |
| Status: | Data Analysis Completed |
| Updated: | 4/2/2008 |
| 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: | Pending |
| 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. |
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| 18. Humoral response of MS patients to the Epstein-Barr virus |
| Judith A. James, M.D., Ph.D. 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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| 19. Antibodies to blood-brain barrier |
| Ben Barres, M.D., Ph.D. 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. |
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| 20. Investigation of myelin damage markers |
| David R. Colman, Ph.D. 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. |
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