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Kevin McRedmond

Other affiliations: Palmetto Health Richland
Bio: Kevin McRedmond is an academic researcher from Palmetto Health. The author has contributed to research in topics: Hemarthrosis & Subclinical infection. The author has an hindex of 5, co-authored 6 publications receiving 1715 citations. Previous affiliations of Kevin McRedmond include Palmetto Health Richland.

Papers
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Journal ArticleDOI
TL;DR: Prophylaxis with recombinant factor VIII can prevent joint damage and decrease the frequency of joint and other hemorrhages in young boys with severe hemophilia A.
Abstract: Sixty-five boys younger than 30 months of age were randomly assigned to prophylaxis (32 boys) or enhanced episodic therapy (33 boys). When the boys reached 6 years of age, 93% of those in the prophylaxis group and 55% of those in the episodic-therapy group were considered to have normal index-joint structure on MRI (P = 0.006). The relative risk of MRI-detected joint damage with episodic therapy as compared with prophylaxis was 6.1 (95% confidence interval, 1.5 to 24.4). The mean annual numbers of joint and total hemorrhages were higher at study exit in the episodic-therapy group than in the prophylaxis group (P<0.001 for both comparisons). High titers of inhibitors of factor VIII developed in two boys who received prophylaxis; three boys in the episodic-therapy group had a life-threatening hemorrhage. Hospitalizations and infections associated with central-catheter placement did not differ significantly between the two groups. Conclusions Prophylaxis with recombinant factor VIII can prevent joint damage and decrease the frequency of joint and other hemorrhages in young boys with severe hemophilia A. (ClinicalTrials.gov number, NCT00207597.)

1,613 citations

Journal ArticleDOI
TL;DR: The results may guide rational design of clinical trials using alternative AAV serotypes and suggest that younger patients who are given AAV gene therapy will benefit from the lower prevalence of NAbs.
Abstract: Recombinant adeno-associated virus (rAAV) is a promising gene delivery vector and has recently been used in patients with hemophilia. One limitation of AAV application is that most humans have experienced wild-type AAV serotype 2 exposure, which frequently generates neutralizing antibodies (NAbs) that may inhibit rAAV2 vector transduction. Employing alternative serotypes of rAAV vectors may circumvent this problem. We investigated the development of NAbs in early childhood by examining sera gathered prospectively from 62 children with hemophilia A, participating in a multi-institutional hemophilia clinical trial (the Joint Outcome Study). Clinical applications in hemophilia therapy have been suggested for serotypes AAV2, AAV5 and AAV8, therefore NAbs against these serotypes were serially assayed over a median follow-up of 4 years. NAbs prevalence increased during early childhood for all serotypes. NAbs against AAV2 (43.5%) were observed more frequently and at higher titers compared with both AAV5 (25.8%) and AAV8 (22.6%). NAbs against AAV5 or AAV8 were rarely observed in the absence of co-prevalent and higher titer AAV2 NAbs, suggesting that NAbs to AAV5 and AAV8 were detected following AAV2 exposure due to partial cross-reactivity of AAV2-directed NAbs. The results may guide rational design of clinical trials using alternative AAV serotypes and suggest that younger patients who are given AAV gene therapy will benefit from the lower prevalence of NAbs.

187 citations

Journal ArticleDOI
TL;DR: The results support the hypothesis that most individuals with the intron 22 inversion are tolerized to FVIII and thus do not develop inhibitors, and a new pharmacogenetic algorithm that permits the stratification of inhibitor risk for individuals and subpopulations is developed.
Abstract: Neutralizing antibodies (inhibitors) to replacement factor VIII (FVIII, either plasma derived or recombinant) impair the effective management of hemophilia A. Individuals with hemophilia A due to major deletions of the FVIII gene (F8) lack antigenically cross-reactive material in their plasma ("CRM-negative"), and the prevalence of inhibitors in these individuals may be as high as 90%. Conversely, individuals with hemophilia A caused by F8 missense mutations are CRM-positive, and their overall prevalence of inhibitors is <10% (ref. 2). Individuals with the F8 intron 22 inversion (found in ∼50% of individuals with severe hemophilia A) have been grouped with the former on the basis of their genetic defect and CRM-negative status. However, only ∼20% of these individuals develop inhibitors. Here we demonstrate that the levels of F8 mRNA and intracellular FVIII protein in B lymphoblastoid cells and liver biopsies from individuals with the intron 22 inversion are comparable to those in healthy controls. These results support the hypothesis that most individuals with the intron 22 inversion are tolerized to FVIII and thus do not develop inhibitors. Furthermore, we developed a new pharmacogenetic algorithm that permits the stratification of inhibitor risk for individuals and subpopulations by predicting the immunogenicity of replacement FVIII using, as input, the number of putative T cell epitopes in the infused protein and the competence of major histocompatibility complex class II molecules to present such epitopes. This algorithm showed statistically significant accuracy in predicting the presence of inhibitors in 25 unrelated individuals with the intron 22 inversion.

60 citations

Journal ArticleDOI
16 Nov 2005-Blood
TL;DR: This first randomized clinical trial of prophylaxis in young children with FVIII deficiency showed improved joint function by age 6 years in children on early every other day prophYLaxis in comparison to an aggressive program of multiple infusions administered promptly at the time of joint hemorrhage.

41 citations

Journal ArticleDOI
James J. Goedert1, Jaime Siegel2, Kay Miller2, Michael M. Lederman3, Alexis A. Thompson4, Brittan Browning4, Susan Gamerman4, Kevin McRedmond5, Janice S. Withycombe5, Ralph A. Gruppo6, Gina Stack6, Jeanne M. Lusher7, Linda Percy7, Diane J. Nugent8, Marianne McDaniel8, Catherine S. Manno9, Regina Butler9, Amanda Wade9, Anne L. Angiolillo10, Naomi L.C. Luban10, Christine Guelcher10, Michael D. Tarantino, Suzi Greer, Joan Cox Gill, Jodie Nelson, Gilbert C. White11, Michael W. Fried11, Aime L. Grimsley11, Donna DiMichele, Ilene Goldberg, James French, Sandra Hibner, James P. Steinberg12, Steven Faust12, Nigel S. Key13, Vicky Hannemann13, Craig M. Kessler14, Anastasia E. Lee14, M. Elaine Eyster15, Kathryn Galli15, Gillian Jenkins15, Zale P. Bernstein, Linda Belling, Amy D. Shapiro, Marge Halley, Patti Noblet, Lawrence Jardine16, Lori Laudenbach16, Richard Lipton17, Christine Pece17, Cindy A. Leissinger18, Cecilia V. Schmidt18, Marcus E. Carr19, Melinda E Nolte19, Marilyn J. Manco-Johnson20, Sheryl Giambartolomei20, Sheldon H. Rubin, Dorine Belliveau, Louis M. Aledort21, Johanna McCarthy21, Richard S. Lemons22, Shirley Bleak22, Eric H. Kraut23, Leslie Witkoff23, Charles Sexauer7, Felicia Kiplinger7, Arthur R. Thompson24, Charles Cooper24, Howard A. Britton7, Kathi Cobb7, Hans Joachim Reimers25, Judy A. Bagato25, Jerry S. Powell, Muriel Herr, Karen Scott, John J. Hutter26, Mary Lou Damiano26, Willis H. Navarro27, Jessie Roth27, J. E. Palascak28, Kenneth E. Sherman28, Madeline Heffner28, Jorge DiPaolo29, Michael Lammer29, Rathi V. Iyer30, Prasad Matthew31, Marcia Schwartz31, Barbara A. Konkle9, Nirmala Vijayanathan9, Marion Dugdale32, Donald Lilley32, Keith Hoots33, Deborah L Brown33, M. Ullman33, Anne T. Neff34, Steven Klintworth34, Hernan Sabio35, Anita Smith35, Anastasia Karafoulidou36 
TL;DR: The scale of hepatic and haematological disease that is likely to manifest in the adult haemophilic population during the coming years unless most of them are successfully treated for HIV‐1, HCV or both is revealed.
Abstract: Before the mid-1980s, haemophilia often was unknowingly treated with contaminated plasma products, resulting in high rates of human immunodeficiency virus (HIV-1), hepatitis C virus (HCV) and hepatitis B virus (HBV) infections. To estimate the impact of these infections, a new cohort was established. All HCV-seropositive patients, age 13-88 years, at 52 comprehensive haemophilia treatment centres were eligible. Cross-sectional data collected during April 2001 to January 2004 (median June 2002) were analysed. Plasma HIV-1 and HCV RNA were quantified by polymerase chain reaction. Highly active antiretroviral therapy (HAART) was defined as use of at least three recommended medications. Among 2069 participants, 620 (30%) had HIV-1. Of 1955 with known HBV status, 814 (42%) had resolved HBV and 90 (4.6%) were HBV carriers. Although 80% of the HIV-1-positive participants had > or = 200 CD4+ cells microL(-1), only 59% were on HAART. HIV-1 RNA was undetectable in 23% of those not taking antiretroviral medications. Most (72%) participants had received no anti-HCV therapy. HCV RNA was detected less frequently (59%) among participants treated with standard interferon plus ribavirin (P = 0.0001) and more frequently among HIV-1-positive than HIV-1-negative participants (85% vs. 70%, P < 0.0001). HIV-1-positive participants were more likely to have pancytopenia and subclinical hepatic abnormalities, as well as persistent jaundice, hepatomegaly, splenomegaly and ascites. HAART recipients did not differ from HIV-negative participants in the prevalence of ascites. The clinical abnormalities were more prevalent with older age but were not confounded by HBV status or self-reported alcohol consumption. Eleven participants presented with or previously had hepatocellular carcinoma or non-Hodgkin lymphoma. Although prospective analysis is needed, our data reveal the scale of hepatic and haematological disease that is likely to manifest in the adult haemophilic population during the coming years unless most of them are successfully treated for HIV-1, HCV or both.

31 citations


Cited by
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Journal ArticleDOI
TL;DR: These evidence‐based guidelines offer practical recommendations on the diagnosis and general management of hemophilia, as well as the management of complications including musculoskeletal issues, inhibitors, and transfusion‐transmitted infections.
Abstract: Hemophilia is a rare disorder that is complex to diagnose and to manage. These evidence-based guidelines offer practical recommendations on the diagnosis and general management of hemophilia, as well as the management of complications including musculoskeletal issues, inhibitors, and transfusion-transmitted infections. By compiling these guidelines, the World Federation of Hemophilia aims to assist healthcare providers seeking to initiate and/or maintain hemophilia care programs, encourage practice harmonization around the world and, where recommendations lack adequate evidence, stimulate appropriate studies.

1,733 citations

Journal ArticleDOI
TL;DR: The prospects and challenges for AAV gene therapy are to a large extent dependent on the target tissue and the specific disease.
Abstract: In vivo gene replacement for the treatment of inherited disease is one of the most compelling concepts in modern medicine. Adeno-associated virus (AAV) vectors have been extensively used for this purpose and have shown therapeutic efficacy in a range of animal models. Successful translation to the clinic was initially slow, but long-term expression of donated genes at therapeutic levels has now been achieved in patients with inherited retinal disorders and haemophilia B. Recent exciting results have raised hopes for the treatment of many other diseases. As we discuss here, the prospects and challenges for AAV gene therapy are to a large extent dependent on the target tissue and the specific disease.

792 citations

Journal ArticleDOI
TL;DR: The WFH Guidelines for the Management of Hemophilia panelists and co-authors thank the panelists for their time and share their views on how to better understand and treat hemophilia.
Abstract: Alok Srivastava 1 | Elena Santagostino 2 | Alison Dougall 3 | Steve Kitchen 4 | Megan Sutherland 5 | Steven W. Pipe 6 | Manuel Carcao 7 | Johnny Mahlangu 8 | Margaret V. Ragni 9 | Jerzy Windyga 10 | Adolfo Llinás 11 | Nicholas J. Goddard 12 | Richa Mohan 13 | Pradeep M. Poonnoose 14 | Brian M. Feldman 15 | Sandra Zelman Lewis 16 | H. Marijke van den Berg 17 | Glenn F. Pierce 18 | on behalf of the WFH Guidelines for the Management of Hemophilia panelists and co-authors*

751 citations

Journal ArticleDOI
04 Jul 2013-Blood
TL;DR: Careful immunosurveillance conducted as part of ongoing clinical studies will provide the basis for understanding the intricacies of the immune response in AAV-mediated gene transfer, facilitating safe and effective therapies for genetic diseases.

682 citations

Journal ArticleDOI
TL;DR: The liver will be used as a model target tissue for gene transfer based on the large amount of data available from preclinical and clinical studies, and key achievements and emerging issues in the field are presented.
Abstract: In recent years, the number of clinical trials in which adeno-associated virus (AAV) vectors have been used for in vivo gene transfer has steadily increased. The excellent safety profile, together with the high efficiency of transduction of a broad range of target tissues, has established AAV vectors as the platform of choice for in vivo gene therapy. Successful application of the AAV technology has also been achieved in the clinic for a variety of conditions, including coagulation disorders, inherited blindness, and neurodegenerative diseases, among others. Clinical translation of novel and effective "therapeutic products" is, however, a long process that involves several cycles of iterations from bench to bedside that are required to address issues encountered during drug development. For the AAV vector gene transfer technology, several hurdles have emerged in both preclinical studies and clinical trials; addressing these issues will allow in the future to expand the scope of AAV gene transfer as a therapeutic modality for a variety of human diseases. In this review, we will give an overview on the biology of AAV vector, discuss the design of AAV-based gene therapy strategies for in vivo applications, and present key achievements and emerging issues in the field. We will use the liver as a model target tissue for gene transfer based on the large amount of data available from preclinical and clinical studies.

548 citations