Treatment of experimental myasthenia gravis with total lymphoid irradiation

Silva, Shari de; Blum, Julia E.; McIntosh, Kevin R.; Order, Stanley E.; Drachman, Daniel B.

doi:10.1016/0090-1229(88)90154-7

Cited by 10 publications

(1 citation statement)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The effect of sex on EAMG has been studied in aged Brown Norway rats where muscle AChR-loss was more prominent in female compared to male rats (Hoedemaekers et al, 1997a). Lewis rats have been more commonly used in EAMG (de Silva et al, 1988; Gomez et al, 2011; Lennon et al, 1978; Lindstrom et al, 1976; Martinez-Martinez et al, 2007; Okumura et al, 1994). Since sex, age and strain are clearly major contributing factors to the severity of EAMG, we recommend standardizing the model by performing the immunization with tAChR in seven-week-old female Lewis rats.…”

Section: Age Sex and Strain Determine Susceptibility Of Rats To Eamgmentioning

confidence: 99%

Standardization of the experimental autoimmune myasthenia gravis (EAMG) model by immunization of rats with Torpedo californica acetylcholine receptors — Recommendations for methods and experimental designs

Losen

Martínez‐Martínez

Molenaar

et al. 2015

Experimental Neurology

View full text Add to dashboard Cite

Myasthenia gravis (MG) with antibodies against the acetylcholine receptor (AChR) is characterized by a chronic, fatigable weakness of voluntary muscles. The production of autoantibodies involves the dysregulation of T cells which provide the environment for the development of autoreactive B cells. The symptoms are caused by destruction of the postsynaptic membrane and degradation of the AChR by IgG autoantibodies, predominantly of the G1 and G3 subclasses. Active immunization of animals with AChR from mammalian muscles, AChR from Torpedo or Electrophorus electric organs, and recombinant or synthetic AChR fragments generates a chronic model of MG, termed experimental autoimmune myasthenia gravis (EAMG). This model covers cellular mechanisms involved in the immune response against the AChR, e.g. antigen presentation, T cell-help and regulation, B cell selection and differentiation into plasma cells. Our aim is to define standard operation procedures and recommendations for the rat EAMG model using purified AChR from the Torpedo californica electric organ, in order to facilitate more rapid translation of preclinical proof of concept or efficacy studies into clinical trials and, ultimately, clinical practice.

show abstract

Section: Age Sex and Strain Determine Susceptibility Of Rats To Eamgmentioning

confidence: 99%

Standardization of the experimental autoimmune myasthenia gravis (EAMG) model by immunization of rats with Torpedo californica acetylcholine receptors — Recommendations for methods and experimental designs

Losen

Martínez‐Martínez

Molenaar

et al. 2015

Experimental Neurology

View full text Add to dashboard Cite

show abstract

Immunotherapy in neuromuscular disorders: Current and future strategies

Drachman

1996

Muscle Nerve

Self Cite

View full text Add to dashboard Cite

Autoimmune mechanisms have recently been implicated in the pathogenesis of an increasing number of neuromuscular diseases. Many of these diseases can be treated with immunotherapeutic agents that are currently available—often with striking success. However, lack of specificity and adverse side effects impose limits on the effectiveness of these immunosuppressive treatments. This article reviews the basic principles of autoimmunity and immune tolerance, and outlines strategies that produce (a) generalized immunosuppression; (b) “selective” immunotherapy; and (c) “antigen‐specific” immunotherapy. General immunosuppressive treatments, which are the ones most commonly used in current practice, down‐regulate the immune system at multiple levels in “shotgun” fashion. The agents described here include: adrenal corticosteroids, azathioprine, cyclophosphamide, chlorambucil, methotrexate, total lymphoid irradiation, plasmapheresis, and intravenous immunoglobulin. “Selective” immunotherapeutic strategies are designed to interfere with mechanisms intrinsic to the immune system. Agents that are now being used clinically, or are in advanced stages of development include: cyclosporin A, which interferes with synthesis of the cytokine interleukin 2 (IL2); IL2 toxin, which binds to IL2 receptors on activated T cells, is endocytosed, and kills the cells; and CTLA41g, which blocks costimulatory molecules, thus preventing full activation of T cells. We have found that combinations of the selective agents may enhance their effectiveness. “Specific” strategies are designed to inactivate or suppress antigen‐specific T cells. Oral administration of autoantigens has been shown to prevent experimental autoimmune diseases specifically, but the conditions required to suppress ongoing autoimmune diseases are capricious and depend on many factors. Finally, we describe a method that is still in the experimental stage, which is designed to modify the individual's own antigen‐presenting cells so that they will target and inactivate antigen‐specific T cells, and thereby turn off the specific autoimmune response. Currently available immunosuppressive methods can now be used successfully to treat many autoimmune neuromuscular diseases, and the application of selective and specific immunotherapeutic strategies promises more precise and effective treatment in the future. © 1996 John Wiley & Sons, Inc.

show abstract

Trial of immunosuppression in amyotrophic lateral sclerosis using total lymphoid irradiation

Drachman

Chaudhry

Cornblath

et al. 1994

Annals of Neurology

Self Cite

View full text Add to dashboard Cite

Although the cause of amyotrophic lateral sclerosis (ALS) remains unknown, recent studies have suggested an autoimmune mechanism of pathogenesis. Previous trials of immunosuppressive treatment have yielded inconclusive results. Our study was designed to determine whether more powerful and prolonged immunosuppression, produced by total lymphoid irradiation (TLI), would alter the course of ALS. In a double-blind, randomized, placebo-controlled study, 30 patients with classic ALS were treated with TLI, and 31 were given sham radiation. Quantitative measurements of muscle strength, functional motor activity, and humoral and cellular immune status were followed for 2 years, or until death or respirator dependence. Motor function in the TLI-treated and control groups showed no significant differences throughout the study. Overall survival was not significantly different in the TLI-treated and control groups. TLI effectively suppressed cellular and humoral immune function throughout the 2-year study period. Analysis of the relationship between immunosuppression and motor functions showed no consistent effect of treatment. We conclude that powerful and prolonged immunosuppression produced by TLI did not benefit patients with ALS. This fails to support the concept of an autoimmune mechanism of pathogenesis of ALS.

show abstract

Treatment of experimental myasthenia gravis with total lymphoid irradiation

Cited by 10 publications

References 33 publications

Standardization of the experimental autoimmune myasthenia gravis (EAMG) model by immunization of rats with Torpedo californica acetylcholine receptors — Recommendations for methods and experimental designs

Standardization of the experimental autoimmune myasthenia gravis (EAMG) model by immunization of rats with Torpedo californica acetylcholine receptors — Recommendations for methods and experimental designs

Immunotherapy in neuromuscular disorders: Current and future strategies

Trial of immunosuppression in amyotrophic lateral sclerosis using total lymphoid irradiation

Contact Info

Product

Resources

About