Post by David Feder on Feb 24, 2006 15:00:37 GMT -5
To Hb:
Treatment with Intravenous Immunoglobulin Improves Muscle Strength in a Patient with Dysferlin-Deficient Muscular Dystrophy
Simone Spuler, Joanna Zabojszcza, Male Friedrich-Freksa, Berlin, Germany
OBJECTIVE: To investigate whether ivig improves muscle strength in dysferlin-deficient muscular dystrophy. BACKGROUND: Recently, we reported that complement inhibitory factor CD55 is downregulated in skeletal muscle of mice and patients with dysferlin-deficient muscular dystrophy (LGMD2B). The absence of CD55 increased susceptibility of dysferlin-deficient human myotubes to complement attack in vitro (Wenzel et al. J Immunol. 2005 Nov 1;175:6219-25). One of the possible therapeutic effects of intravenous immunoglobulines (ivig) is inhibition of complement factors C4 and C5. We therefore tested whether ivig might be beneficial in LGMD2B. DESIGN/METHODS: As compassionate use a single female 32 year old patient with dysferlin-deficient muscular dystrophy was treated with ivig (Intraglobin, Biotest AG, Taunus, Germany) for six months after informed consent was obtained. After an induction cycle of 0.4 g/kg body weight for 5 days ivig was applied once a month at 0.4 g/kg body weight. Muscle strength was tested by manual muscle testing. A muscle biopsy specimen was analysed before and after treatment for deposition of sarcolemmal C5b9 membrane attack complex. RESULTS: Ivig was tolerated well. After three months the patient reported a marked improvement in her ability to walk and in her strength when holding a heavy bag. Muscle strength improved further until treatment-month six. All muscle groups tested improved during treatment, some muscles such as the tibial anterior muscle improved from grade of paresis of 2/5 to almost full strength at 4-5/5. C5b9 membrane attack complex, present on almost all muscle fibres in the pretreatment muscle specimen, were nearly absent in muscle obtained after treatment. CONCLUSIONS/RELEVANCE: The effect of ivig in LGMD2B should be tested in a controlled clinical trial.
Treatment with Intravenous Immunoglobulin Improves Muscle Strength in a Patient with Dysferlin-Deficient Muscular Dystrophy
Simone Spuler, Joanna Zabojszcza, Male Friedrich-Freksa, Berlin, Germany
OBJECTIVE: To investigate whether ivig improves muscle strength in dysferlin-deficient muscular dystrophy. BACKGROUND: Recently, we reported that complement inhibitory factor CD55 is downregulated in skeletal muscle of mice and patients with dysferlin-deficient muscular dystrophy (LGMD2B). The absence of CD55 increased susceptibility of dysferlin-deficient human myotubes to complement attack in vitro (Wenzel et al. J Immunol. 2005 Nov 1;175:6219-25). One of the possible therapeutic effects of intravenous immunoglobulines (ivig) is inhibition of complement factors C4 and C5. We therefore tested whether ivig might be beneficial in LGMD2B. DESIGN/METHODS: As compassionate use a single female 32 year old patient with dysferlin-deficient muscular dystrophy was treated with ivig (Intraglobin, Biotest AG, Taunus, Germany) for six months after informed consent was obtained. After an induction cycle of 0.4 g/kg body weight for 5 days ivig was applied once a month at 0.4 g/kg body weight. Muscle strength was tested by manual muscle testing. A muscle biopsy specimen was analysed before and after treatment for deposition of sarcolemmal C5b9 membrane attack complex. RESULTS: Ivig was tolerated well. After three months the patient reported a marked improvement in her ability to walk and in her strength when holding a heavy bag. Muscle strength improved further until treatment-month six. All muscle groups tested improved during treatment, some muscles such as the tibial anterior muscle improved from grade of paresis of 2/5 to almost full strength at 4-5/5. C5b9 membrane attack complex, present on almost all muscle fibres in the pretreatment muscle specimen, were nearly absent in muscle obtained after treatment. CONCLUSIONS/RELEVANCE: The effect of ivig in LGMD2B should be tested in a controlled clinical trial.
