This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Contact me when this article is cited  Related Content  • Related article  • Similar articles in this journal  Topic Collections  • Multiple Sclerosis/ Demyelinating Disease  • Randomized Controlled Trial  • Immunologic Disorders  • Alert me on articles by topic  Social Bookmarking   What's this?

Amit Bar-Or, MD; Timothy Vollmer, MD; Jack Antel, MD; Douglas L. Arnold, MD; Caroline Anita Bodner, MSc; Denise Campagnolo, MD; Jill Gianettoni, BS; Farzaneh Jalili, BSc; Norman Kachuck, MD; Yves Lapierre, MD; Masaaki Niino, MD, PhD; Joel Oger, MD; Mary Price, BS; Susan Rhodes, MS; William H. Robinson, MD, PhD; Fu-Dong Shi, MD, PhD; Paul J. Utz, MD; Frank Valone, MD; Leslie Weiner, MD; Lawrence Steinman, MD; Hideki Garren, MD, PhD

Arch Neurol. 2007;64:(doi:10.1001/archneur.64.10.nct70002).

Objective  To assess safety and immune modulation by BHT-3009, a tolerizing DNA vaccine encoding full-length human myelin basic protein, in patients with multiple sclerosis (MS).

Design  The study was a randomized, double-blind, placebo-controlled trial. Subjects receiving placebo were crossed over into an active arm after treatment unblinding.

Setting  The trial was conducted at 4 academic institutions within North America.

Patients  Thirty patients with relapsing-remitting or secondary progressive MS who were not taking any other disease-modifying drugs were enrolled in the trial. Further, the patients were required to have either 1 to 5 gadolinium-enhancing lesions on screening brain magnetic resonance imaging (MRI), a relapse in the previous 2 years, or disease worsening in the previous 2 years.

Interventions  BHT-3009 was administered as intramuscular injections at weeks 1, 3, 5, and 9 after randomization into the trial, with or without 80 mg of daily oral atorvastatin calcium in combination. Three dose levels of BHT-3009 were tested (0.5 mg, 1.5 mg, and 3 mg).

Main Outcome Measures  The primary outcome measures were safety and tolerability of BHT-3009. Secondary outcome measures included the number and volume of gadolinium-enhanced lesions on MRI, relapses, and analysis of antigen-specific immune responses.

Results  BHT-3009 was safe and well tolerated, provided favorable trends on brain MRI, and produced beneficial antigen-specific immune changes. These immune changes consisted of a marked decrease in proliferation of interferon-–producing, myelin-reactive CD4+ T cells from peripheral blood and a reduction in titers of myelin-specific autoantibodies from cerebral spinal fluid as assessed by protein microarrays. We did not observe a substantial benefit of the atorvastatin combination compared with BHT-3009 alone.

Conclusion  In patients with MS, BHT-3009 is safe and induces antigen-specific immune tolerance with concordant reduction of inflammatory lesions on brain MRI.

Trial Registration  clinicaltrials.gov Identifier: NCT00103974.

Author Affiliations: Montreal Neurological Institute (Drs Bar-Or, Antel, Lapierre, and Niino and Mss Bodner and Jalili) and NeuroRx Research (Dr Arnold), Montreal, Quebec, Canada; Barrow Neurological Institute, Phoenix, Arizona (Drs Vollmer, Campagnolo, and Shi and Mss Price and Rhodes); Bayhill Therapeutics, Inc, Palo Alto, California (Ms Gianettoni and Drs Valone and Garren); University of Southern California, Los Angeles (Drs Kachuck and Weiner); University of British Columbia, Vancouver, British Columbia, Canada (Dr Oger); and Stanford University, Stanford, California (Drs Robinson, Utz, Steinman, and Garren).

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

RELATED ARTICLE

DNA Plasmid Vaccination for Multiple Sclerosis
Olaf Stüve, Todd N. Eagar, Elliot M. Frohman, and Petra D. Cravens
Arch Neurol. 2007;64(10):1385-1386.
EXTRACT | FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Inflammatory Proprotein Convertase-Matrix Metalloproteinase Proteolytic Pathway in Antigen-presenting Cells as a Step to Autoimmune Multiple Sclerosis
Shiryaev et al.
J. Biol. Chem. 2009;284:30615-30626.
ABSTRACT | FULL TEXT  

Emerging Therapies for Relapsing Multiple Sclerosis
Cohen
Arch Neurol 2009;66:821-828.
ABSTRACT | FULL TEXT  

Autoantibody Profiling in Multiple Sclerosis Reveals Novel Antigenic Candidates
Somers et al.
J. Immunol. 2008;180:3957-3963.
ABSTRACT | FULL TEXT  

DNA Plasmid Vaccination for Multiple Sclerosis
Stuve et al.
Arch Neurol 2007;64:1385-1386.
FULL TEXT