Multiple Sclerosis: Richert JR

Polman CH, Reingold SC, Barkhof F, Calabresi PA, Clanet M, Cohen JA, Cutter GR, Freedman MS, Kappos L, Lublin FD, McFarland HF, Metz LM, Miller AE, Montalban X, O'Connor PW, Panitch H, Richert JR, Petkau J, Schwid SR, Sormani MP, Thompson AJ, Weinshenker BG, Wolinsky JS. · Department of Neurology, Free University Medical Center in Amsterdam, PO Box 4075, 1007 MB Amsterdam, The Netherlands. · Neurology. · Pubmed #18362273 No free full text.

Abstract: The increasing number of established effective therapies for relapsing multiple sclerosis (MS) and emerging consensus for early treatment raise practical concerns and ethical dilemmas for placebo-controlled clinical trials in this disease. An international group of clinicians, ethicists, statisticians, regulators, and representatives from the pharmaceutical industry convened to reconsider prior recommendations regarding the ethics of placebo-controlled trials in MS. The group concluded that placebo-controlled trials can still be done ethically, with restrictions. For patients with relapsing MS for which established effective therapies exist, placebo-controlled trials should only be offered with rigorous informed consent if the subjects refuse to use these treatments, have not responded to them, or if these treatments are not available to them for other reasons (e.g., economics). Suggestions are provided to protect subject autonomy and improve informed consent procedures. Recommendations are tighter than previously suggested for placebo-controlled trials in "resource-restricted" environments where established therapies may not be available. Guidance is also provided on the ethics of alternative trial designs and the balance between study subject burden and risk, scientific rationale and interpretability of trial outcomes.

Stuart WH, Cohan S, Richert JR, Achiron A. · Peachtree Neurological Clinic, 3200 Downwood Circle, Suite 550, Atlanta, Georgia 30327, USA. · Neurology. · Pubmed #15596732 No free full text.

Abstract: Multiple sclerosis (MS) is a complex, incurable disease. Treatment consists of lifelong disease and symptom management. FDA-approved therapies for relapsing MS include subcutaneous (SC) interferon beta-1b (IFNbeta1b, Betaseron), IM interferon-beta-1a (Avonex), SC interferon-beta-1a (Rebif), glatiramer acetate (Copaxone), and mitoxantrone (Novantrone), all of which are known as disease-modifying agents (DMAs). DMAs that can be initiated and continued on a long-term basis can be referred to as platform therapies. During periods of disease instability with increased disease activity, corticosteroids or immunosuppressive agents can be used in combination with appropriate DMA platform therapy to help control symptoms. To date, long-term comparative studies of DMAs are not available. However, based on the effects of these agents on disability progression, relapse rates, MRI outcomes, and neutralizing antibodies observed in phase III randomized clinical trials, IFNbeta1a products are the DMAs of choice for platform therapy for MS. Evidence indicates that IFNbeta1a may also be beneficial in the early stages of the disease. Research is ongoing to identify other appropriate add-on agents (e.g., antigen-specific therapies) to be used in combination with existing DMAs to effectively manage MS.

Castro HJ, Mendez-Lnocencio JI, Omidvar B, Omidvar J, Santilli J, Nielsen HS, Pavot AP, Richert JR, Bellanti JA. · International Center for Interdisciplinary Studies of Immunology and the Departments of Pediatrics, Georgetown University School of Medicine, Washington, DC, USA. · Allergy Asthma Proc. · Pubmed #16541972 No free full text.

Abstract: Although several reports suggest that bee venom may be an effective treatment for patients with multiple sclerosis (MS), patients may be subjected to real risks of serious allergic reactions as well as emotional and economic costs. This study was conducted to evaluate the safety of bee venom extract as a possible treatment for patients with progressive forms of MS. A total of nine bee venom nonallergic patients with progressive forms of MS, who were 21-55 years of age with no other illnesses, were entered into four groups (A, B, C, and D) on a structured 1-year immunization schedule. Hyperreactivity to bee venom was evaluated by questionnaire, physical examination, and a battery of hematologic, metabolic, and immunologic tests. Responses to therapy were evaluated by questionnaire, functional neurological tests, and changes in measurement of somatosensory-evoked potentials. Although no serious adverse allergic reactions were observed in any of the nine subjects, four experienced worsening of neurological symptoms, requiring termination in the study; this could not be ascribed to side effects of the therapy. Of the remaining five subjects, three felt that the therapy had subjective amelioration of symptoms and two showed objective improvement. Although this preliminary study suggests safety, because of the small numbers studied, there were no definite conclusions regarding efficacy and therefore there was little evidence to support the use of honeybee venom in the treatment of MS. Larger and more carefully conducted multicenter studies will be required to establish efficacy.

Herndon RM, Rudick RA, Munschauer FE, Mass MK, Salazar AM, Coats ME, Labutta R, Richert JR, Cohan SL, Genain C, Goodkin D, Toal M, Riester K. · University of Mississippi, VA Medical Center, Jackson, MS 39216, USA. · Mult Scler. · Pubmed #16042223 No free full text.

Abstract: An open-label extension study of the phase III trial of intramuscular interferon beta-1a (IFNbeta-1a-Avonex) was conducted to evaluate the immunogenicity and safety of IFNbeta-1a-Avonex over six years in patients with relapsing multiple sclerosis (MS). Patients who participated in the pivotal phase III study were offered enrolment; entry was also open to patients who had not participated. All patients received IFNbeta-1a-Avonex 30 microg intramuscularly once weekly for six years, for a treatment duration of up to eight years in patients who received IFNbeta-1a-Avonex in the phase III trial. Serum levels of IFNbeta antibodies were measured every six months using a screening enzyme-linked immunosorbent assay (ELISA) followed by an antiviral cytopathic effect assay to detect neutralizing antibodies (NAbs) in serum samples positive on ELISA. The incidence of adverse events and laboratory test results assessed safety. Of 382 total patients, 218 had participated in the phase III study (103 placebo, 115 IFNbeta-1a-Avonex) and 164 had not participated; 24 of the 164 were IFNbeta-naïve. At baseline, 281 patients were negative for IFNbeta antibodies (NAb-). NAbs (titre > or = 20) developed at any time over six years in 5% of these patients. Of 140 patients who had been on IFNbeta-1b-Betaseron, 49 were positive for NAbs (NAb+) at baseline; 11 of 115 who had been on IFNbeta-1a-Avonex were NAb+ at baseline. Thirty-nine of 49 patients who had been on Betaseron and were NAb+ had titres < 100; 36 of these 39 seroconverted to NAb- while on IFNbeta-1a-Avonex, with a median time of approximately six months. Ten patients who had been on Betaseron had NAb titres > or = 100; five remained NAb+ during six years on IFNbeta-1a-Avonex and five seroconverted to NAb-, but only after at least two years. Five patients who had been on IFNbeta-1a-Avonex during the clinical trial were NAb+ with titres < 100 at baseline; four seroconverted to NAb-, with a median time of two to three years. Six patients who had been on IFNbeta-1a-Avonex had NAb titres > or = 100; five of these remained NAb+ at six years. No patient with a NAb titre > 1000 seroconverted to NAb-, whether initially treated with IFNbeta-1a-Avonex or -Betaseron. Adverse events were similar to those observed in the pivotal phase III trial. Results from this trial indicated that IFNbeta-1a-Avonex was associated with a low incidence of NAbs and was well tolerated for up to eight years. Further, the results indicate that persistence of NAbs is dependent on titre and IFNbeta product.

Simon JH, Lull J, Jacobs LD, Rudick RA, Cookfair DL, Herndon RM, Richert JR, Salazar AM, Sheeder J, Miller D, McCabe K, Serra A, Campion MK, Fischer JS, Goodkin DE, Simonian N, Lajaunie M, Wende K, Martens-Davidson A, Kinkel RP, Munschauer FE. · Department of Radiology-MRI, University of Colorado Health Sciences Center, Denver, USA. · Neurology. · Pubmed #10908888 No free full text.

Abstract: BACKGROUND: T1 hypointense lesions (T1 black holes) are focal areas of relatively severe CNS tissue damage detected by MRI in patients with MS. OBJECTIVE: To determine the natural history of T1 hypointense lesions in relapsing MS and the utility of T1 hypointense lesions as outcome measures in MS clinical trials. METHODS: MR studies were from the Multiple Sclerosis Collaborative Research Group trial. Longitudinal results are reported in 80 placebo- and 80 interferon beta-1a (IFNbeta-1a)-treated patients with mild to moderate disability relapsing-remitting MS. RESULTS: There was a small but significant correlation between T1 hypointense lesion volume and disability at baseline and on trial (r = 0.22, r = 0.28). In placebo patients there was a 29.2% increase in the mean volume of T1 hypointense lesions (median 124.5 mm3) over 2 years (p < 0.001 for change from baseline), as compared to an 11.8% increase (median 40 mm3) in the IFNbeta-1a-treated patients (change from baseline not significant). These treatment group comparisons did not quite reach significance. The most significant contributor to change in T1 hypointense lesions was the baseline number of enhancing lesions (model r2 = 0.554). Placebo patients with more active disease, defined by enhancing lesions at baseline, were the only group to show a significant increase in T1 hypointense lesion volume from baseline. CONCLUSION: The development of T1 hypointense lesions is strongly influenced by prior inflammatory disease activity, as indicated by enhancing lesions. These results suggest that treatment with once weekly IM IFNbeta-1a (30 mcg) slows the 2-year accumulation of these lesions in the brain.

Simon JH, Jacobs LD, Campion MK, Rudick RA, Cookfair DL, Herndon RM, Richert JR, Salazar AM, Fischer JS, Goodkin DE, Simonian N, Lajaunie M, Miller DE, Wende K, Martens-Davidson A, Kinkel RP, Munschauer FE, Brownscheidle CM. · Department of Radiology-MRI, University of Colorado Health Sciences Center, Denver 80262, USA. · Neurology. · Pubmed #10408550 No free full text.

Abstract: OBJECTIVE: To determine if progressive brain atrophy could be detected over 1- and 2-year intervals in relapsing MS, based on annual MR studies from the Multiple Sclerosis Collaborative Research Group (MSCRG) trial of interferon beta-1a (Avonex). METHODS: All subjects had mild to moderate disability, with baseline expanded disability status scores ranging from 1.0 to 3.5, and at least two relapses in the 3 years before study entry. Atrophy measures included third and lateral ventricle width, brain width, and corpus callosum area. RESULTS: Significant increases were detected in third ventricle width at year 2 and lateral ventricle width at 1 and 2 years. Significant decreases in corpus callosum area and brain width were also observed at 1 and 2 years. Multiple regression analyses suggested that the number of gadolinium-enhancing lesions at baseline was the single significant contributor to change in third ventricle width. Atrophy over 1 and 2 years as indicated by enlargement of the third and lateral ventricle and shrinkage of the corpus callosum was greater for patients entering the trial with enhancing lesions. Greater disability increments over 1 and 2 years were associated with more severe third ventricle enlargement. CONCLUSION: In patients with relapsing MS and only mild to moderate disability, significant cerebral atrophy is already developing that can be measured over periods of only 1 to 2 years. The course of cerebral atrophy in MS appears to be influenced by prior inflammatory disease activity as indicated by the presence of enhancing lesions. Brain atrophy measures are important markers of MS disease progression because they likely reflect destructive and irreversible pathologic processes.

Rudick RA, Cookfair DL, Simonian NA, Ransohoff RM, Richert JR, Jacobs LD, Herndon RM, Salazar AM, Fischer JS, Granger CV, Goodkin DE, Simon JH, Bartoszak DM, Bourdette DN, Braiman J, Brownscheidle CM, Coats ME, Cohan SL, Dougherty DS, Kinkel RP, Mass MK, Munchsauer FE, O'Reilly K, Priore RL, Whitham RH. · Mellen Center For Multiple Sclerosis Treatment and Research, Department of Neurology, The Cleveland Clinic Foundation, OH 44106, USA. · J Neuroimmunol. · Pubmed #10378864 No free full text.

Abstract: BACKGROUND AND OBJECTIVE: This report provides results of CSF analyses done in a subset of relapsing remitting MS patients participating in a placebo-controlled, double-blind, phase III clinical trial of IFNbeta-Studies supported by the National Multiple Sclerosis Society (grants RG2019, RG2827),a (Avonex , Biogen). The clinical trial demonstrated that IFNbeta-1a treatment resulted in significantly reduced disability progression, annual relapse rate, and new brain lesions visualized by cranial magnetic resonance imaging. The objectives of the current study were to determine: (a) whether CSF abnormalities in MS patients correlated with disease or MRI characteristics, and (b) effects of IFNbeta-1a therapy on these CSF abnormalities. METHODS: CSF was analyzed from 262 (87%) of the 301 study subjects at entry into the clinical trial, and a second CSF sample was analyzed from 137 of these 262 subjects after 2 years of therapy. CSF cell counts, oligoclonal bands (OCB), IgG index, and free kappa light chains were measured using standard assays. Baseline CSF results were compared with demographic, disease, and MRI parameters. Differences in on-study relapse rate, gadolinium enhancement, and EDSS change according to baseline CSF status was used to determine the predictive value of CSF for subsequent clinical and MRI disease activity. Change in CSF parameters after 104 weeks were used to determine the effects of treatment. RESULTS: (1) At study baseline, 37% of the subjects had abnormal CSF WBC counts, 61% had abnormal levels of CSF free kappa light chains, 84% had abnormal IgG index values, and 90% were positive for OCB. (2) Baseline IgG index, kappa light chains, and OCB showed weakly positive, statistically significant correlations with Gd-enhanced lesion volume and T2 lesion volume. WBC showed a statistically significant correlation with Gd-enhancing lesion volume but was uncorrelated with T2 lesion volume. (3) There was an associated between baseline CSF WBC counts and on-study clinical and MRI disease activity in placebo recipients. (4) IFNbeta-1a treatment resulted in significantly reduced CSF WBC counts, but there was no treatment-related change in CSF IgG index, kappa light chains, or OCB, which remained relatively stable over time in both patient groups. CONCLUSIONS: The current study documents significant reductions in CSF WBC counts in patients treated with IFNbeta-1a for 104 weeks. This finding is considered relevant to the therapeutic response, since CSF WBC counts were found to be positively correlated with subsequent clinical and MRI disease activity in placebo-treated relapsing MS patients.

Mehta LR, Schwid SR, Arnold DL, Cutter GR, Aradhye S, Balcer LJ, Calabresi PA, Cohen JA, Cole PE, Glanzman R, Goelz S, Inglese M, Kapoor R, Kappos L, Kreitman R, Lublin FD, Mann A, Marrie RA, O'Looney P, Polman CH, Ravina BM, Reingold SC, Richert JR, Sandrock AW, Waubant E. · University of Rochester Department of Neurology, Rochester, NY, USA. · Mult Scler. · Pubmed #19389749 No free full text.

Abstract: BACKGROUND: There is considerable interest in tissue-protective treatments for multiple sclerosis (MS). METHODS AND OBJECTIVES: We convened a group of MS clinical trialists and related researchers to discuss designs for proof of concept studies utilizing currently available data and assessment methods. RESULTS: Our favored design was a randomized, double-blind, parallel-group study of active treatment versus placebo focusing on changes in brain volume from a post-baseline scan (3-6 months after starting treatment) to the final visit 1 year later. Study designs aimed at reducing residual deficits following acute exacerbations are less straightforward, depending greatly on the anticipated rapidity of treatment effect onset. CONCLUSIONS: The next step would be to perform one or more studies of potential tissue-protective agents with these designs in mind, creating the longitudinal data necessary to refine endpoint selection, eligibility criteria, and sample size estimates for future trials.

Miller DH, Weinshenker BG, Filippi M, Banwell BL, Cohen JA, Freedman MS, Galetta SL, Hutchinson M, Johnson RT, Kappos L, Kira J, Lublin FD, McFarland HF, Montalban X, Panitch H, Richert JR, Reingold SC, Polman CH. · Department of Inflammation, Institute of Neurology, NMR Research Unit, University College London, UK. · Mult Scler. · Pubmed #18805839 No free full text.

Abstract: BACKGROUND AND OBJECTIVES: Diagnosis of multiple sclerosis (MS) requires exclusion of diseases that could better explain the clinical and paraclinical findings. A systematic process for exclusion of alternative diagnoses has not been defined. An International Panel of MS experts developed consensus perspectives on MS differential diagnosis. METHODS: Using available literature and consensus, we developed guidelines for MS differential diagnosis, focusing on exclusion of potential MS mimics, diagnosis of common initial isolated clinical syndromes, and differentiating between MS and non-MS idiopathic inflammatory demyelinating diseases. RESULTS: We present recommendations for 1) clinical and paraclinical red flags suggesting alternative diagnoses to MS; 2) more precise definition of "clinically isolated syndromes" (CIS), often the first presentations of MS or its alternatives; 3) algorithms for diagnosis of three common CISs related to MS in the optic nerves, brainstem, and spinal cord; and 4) a classification scheme and diagnosis criteria for idiopathic inflammatory demyelinating disorders of the central nervous system. CONCLUSIONS: Differential diagnosis leading to MS or alternatives is complex and a strong evidence base is lacking. Consensus-determined guidelines provide a practical path for diagnosis and will be useful for the non-MS specialist neurologist. Recommendations are made for future research to validate and support these guidelines. Guidance on the differential diagnosis process when MS is under consideration will enhance diagnostic accuracy and precision.

Koehler NK, Yang CY, Varady J, Lu Y, Wu XW, Liu M, Yin D, Bartels M, Xu BY, Roller PP, Long YQ, Li P, Kattah M, Cohn ML, Moran K, Tilley E, Richert JR, Wang S. · Departments of Microbiology and Immunology, Neurology, and Pathology, Georgetown University Medical Center, Washington, D.C. 20007, USA. · J Med Chem. · Pubmed #15456243 No free full text.

Abstract: We have utilized a computational structure-based approach to identify nonpeptidic small organic compounds that bind to a human leukocyte antigen (HLA) DR1301 molecule (HLA-DR1301 or DR1301) and block the presentation of myelin basic protein peptide 152-165 (MBP 152-165) to T cells. A three-dimensional (3D) structure of DR1301 was derived by homology modeling followed by extensive molecular dynamics simulation for structural refinement. Computational structure-based database searching was performed to identify nonpeptidic small-molecule candidates from the National Cancer Institute (NCI) database containing over 150 000 compounds that can effectively interact with the peptide-binding groove of the HLA molecule. By in vitro testing of 106 candidate small molecules, two lead compounds were confirmed to specifically block IL-2 secretion by DR1301-restricted T cells in a dose-dependent and reversible manner. The specificity of blocking DR1301-restricted MBP presentation was further validated in a binding assay using an analogue of the most potent lead compound. Computational docking was performed to predict the three-dimensional binding model of these confirmed small molecule blockers to the DR1301 molecule and to gain structural insight into their interactions. Our results suggest that computational structure-based searching is an effective approach to discover nonpeptidic small organic compounds to block the interaction between DR1301 and T cells. The nonpeptidic small organic compounds identified in this study are useful pharmacological tools to study the interactions between HLA molecules and T cells and a starting point for the development of a novel therapeutic strategy for the treatment of multiple sclerosis (MS) or other immune-related disorders.

Grekova MC, Salerno K, Mikkilineni R, Richert JR. · Department of Microbiology and Immunology, Georgetown University Medical Center, Washington DC 20007, USA. · Lab Invest. · Pubmed #12218073 No free full text.

Abstract: We previously reported the lack of expression of the bifunctional transcription factor Sp3 in peripheral blood mononuclear cells from most patients with multiple sclerosis (MS) (Grekova et al, 1996). An RT-PCR technique was developed to evaluate Sp3 mRNA levels in peripheral blood mononuclear cell subsets. Semi-quantitative and quantitative competitive RT-PCR assays were used to compare the level of Sp3 expression among subjects and among immune cell subsets. The competitor DNA fragment contained a deletion from the normal Sp3 cDNA sequence. The wild-type Sp3 cDNA and the competitor DNA fragment amplified with equal efficiency, and the two PCR products were distinguished by size. These studies demonstrated that normal CD4(+) and CD8(+) T cells, B cells, and macrophages expressed comparable amounts of Sp3 mRNA. No Sp3 expression could be detected in normal natural killer cells nor in any of these cell types from Sp3-negative MS patients. We propose that transcription of the Sp3 gene is blocked in immune cells from most patients with MS and that this contributes to the development of central nervous system inflammation in the disease.

Rudick RA, Goodkin DE, Jacobs LD, Cookfair DL, Herndon RM, Richert JR, Salazar AM, Fischer JS, Granger CV, Simon JH, Alam JJ, Simonian NA, Campion MK, Bartoszak DM, Bourdette DN, Braiman J, Brownscheidle CM, Coats ME, Cohan SL, Dougherty DS, Kinkel RP, Mass MK, Munschauer FE, Priore RL, Pullicino PM, Scherokman BJ, Weistock-Guttman B, Whitham RH, Anonymous00280. · No affiliation provided · Neurology. · Pubmed #11902591 No free full text.

This publication has no abstract.

Mohan N, Edwards ET, Cupps TR, Oliverio PJ, Sandberg G, Crayton H, Richert JR, Siegel JN. · Georgetown University Medical Center, Washington, DC 20007, USA. · Arthritis Rheum. · Pubmed #11762947 No free full text.

Abstract: OBJECTIVE: To review the occurrence of neurologic events suggestive of demyelination during anti-tumor necrosis factor alpha (anti-TNFalpha) therapy for inflammatory arthritides. METHODS: The Adverse Events Reporting System of the Food and Drug Administration (FDA) was queried following a report of a patient with refractory rheumatoid arthritis who developed confusion and difficulty with walking after receiving etanercept for 4 months. RESULTS: Nineteen patients with similar neurologic events were identified from the FDA database, 17 following etanercept administration and 2 following infliximab administration for inflammatory arthritis. All neurologic events were temporally related to anti-TNFalpha therapy, with partial or complete resolution on discontinuation. One patient exhibited a positive rechallenge phenomenon. CONCLUSION: Further surveillance and studies are required to better define risk factors for and frequency of adverse events and their relationship to anti-TNFalpha therapies. Until more long-term safety data are available, consideration should be given to avoiding anti-TNFalpha therapy in patients with preexisting multiple sclerosis and to discontinuing anti-TNFalpha therapy immediately when new neurologic signs and symptoms occur, pending an appropriate evaluation.

Fischer JS, Priore RL, Jacobs LD, Cookfair DL, Rudick RA, Herndon RM, Richert JR, Salazar AM, Goodkin DE, Granger CV, Simon JH, Grafman JH, Lezak MD, O'Reilly Hovey KM, Perkins KK, Barilla-Clark D, Schacter M, Shucard DW, Davidson AL, Wende KE, Bourdette DN, Kooijmans-Coutinho MF. · Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, OH, USA. · Ann Neurol. · Pubmed #11117545 No free full text.

Abstract: Cognitive dysfunction is common in multiple sclerosis (MS), yet few studies have examined effects of treatment on neuropsychological (NP) performance. To evaluate the effects of interferon beta-1a (IFNbeta-1a, 30 microg administered intramuscularly once weekly [Avonex]) on cognitive function, a Comprehensive NP Battery was administered at baseline and week 104 to relapsing MS patients in the phase III study, 166 of whom completed both assessments. A Brief NP Battery was also administered at 6-month intervals. The primary NP outcome measure was 2-year change on the Comprehensive NP Battery, grouped into domains of information processing and learning/memory (set A), visuospatial abilities and problem solving (set B), and verbal abilities and attention span (set C). NP effects were most pronounced in cognitive domains vulnerable to MS: IFNbeta-1a had a significant beneficial effect on the set A composite, with a favorable trend evident on set B. Secondary outcome analyses revealed significant between-group differences in slopes for Brief NP Battery performance and time to sustained deterioration in a Paced Auditory Serial Addition Test processing rate, favoring the IFNbeta-1a group. These results support and extend previous observations of significant beneficial effects of IFNbeta-1a for relapsing MS.

Baker AM, Grekova MC, Richert JR. · Departments of Microbiology and Immunology, Georgetown University Medical Center, Washington, DC 20007, USA. · J Neurosci Res. · Pubmed #10878586 No free full text.

Abstract: The in vivo study of immunologic mechanisms in experimental allergic encephalomyelitis (EAE) requires, in some instances, the use of transgenic mice. As FVB mice represent a strain whose fertilized ova possess a relatively large pronucleus, this is a preferred strain in which to generate mice that are transgenic for a variety of genes. An important issue, then, is whether the FVB background supports the development of EAE. We report here that relapsing EAE is easily and reproducibly induced in FVB mice with whole myelin basic protein in complete Freund's adjuvant.

Grekova MC, Scherer SW, Trabb J, Richert JR. · Department of Microbiology and Immunology, Georgetown University, Medical Center, Washington, DC 2007, USA. · J Neuroimmunol. · Pubmed #10814800 No free full text.

Abstract: Sp3 belongs to a large family of transcription factors that bind GC/T box elements. We have previously demonstrated the deficient expression of Sp3 in peripheral blood mononuclear cells (PBMC) from most patients with multiple sclerosis (MS). In the current study, the Sp3 gene was assigned to chromosome 7 by using somatic cell hybrid mapping and analysis of a chromosome 7-specific cosmid library. The position of Sp3 was refined to 7p14-p15.2 by fluorescence in situ hybridization (FISH). Southern blot and polymerase chain reaction analysis of genomic DNA failed to demonstrate a detectable difference between MS and control PBMC.