MG Studies
Brenner Studies
Buschman Studies
Kusner Studies

Abramsky/Brenner Studies

Experimental Design

  • Female Lewis rats with experimental autoimmune myasthenia gravis (EAMG) induced by injections of Ach-torpedo preparation were treated with alpha-fetoprotein to explore the therapeutic value of AFP
    • Control Group: saline (n=26)
    • Chronic Phase Group: rhAFP 60µg/kg/day from day 26 post-induction (n=26)
  • Sera from the rats were assayed for anti-rat AChR antibodies and the rats were given a clinical severity score 0-5 based upon inspection for muscle weakness
  • Dosage chosen to mimic AFP level during remission of autoimmunity in the 2nd half of human pregnancy

Results

  • Statistically significant reductions in disease severity and incidence were observed following rhAFP treatment
    • EAMG rats treated with AFP showed normal response to repetitive nerve stimulations, compared to placebo-controlled EAMG rats who showed a decreased response
    • Levels of anti-AChR antibodies directed against rat-AChR were lowered by 62% in the treated rats
  • In the Chronic Phase Group, the natural course of gradual disease progression did not occur

Brenner T. The effect of rhAFP on experimental Myasthenia gravis (EAMG) in Lewis rats. Results Summary.

Buschman Studies

In Vivo Survival Study

  • EAMG - the “gold standard” model for MG
  • Induced by passive transfer of autoantibodies
  • Mouse AFP used to avoid immune response
  • Results suggest that chronic treatment with AFP needed to maintain benefits
Buschman et al 1987

Kusner Studies

George Washington University

Study Design

Objective

To evaluate the efficacy of ACT-101 in an experimental autoimmune MG rat model.

Experimental Design

  • Experimental autoimmune MG was induced in 25 Lewis Female rats with tAChR
  • On day 40 after induction, daily intraperitoneal injections of ACT-101 (60 mcg or 1 mg) or equivalent volume of placebo (PBS) was initiated
  • After 14 days of treatment, EAMG rats were euthanized and samples were taken

Results Summary

  • EAMG rats that received 1 mg of ACT-101 demonstrated lower clinical scores and greater grip strength than control rats
  • Complement-activating anti-AChR IgG2 levels were significantly lower in AFP-treated rats while non-complement activating IgG1 levels were not reduced

Kusner