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Complement inhibition abrogates nerve terminal injury in Miller Fisher syndrome
Author(s) -
Halstead Susan K.,
Humphreys Peter D.,
Goodfellow John A.,
Wagner Eric R.,
Smith Richard A. G.,
Willison Hugh J.
Publication year - 2005
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.20546
Subject(s) - axon , complement system , neuroprotection , schwann cell , in vivo , guillain barre syndrome , neuroscience , complement membrane attack complex , neuromuscular junction , axon terminal , miller fisher syndrome , in vitro , immunology , medicine , microbiology and biotechnology , biology , antibody , biochemistry
A large body of clinical and experimental data indicate that complement activation is an important mechanism for neuronal and glial injury in Guillain–Barré syndromes. Inhibition of complement activation therefore might be expected to limit the progression of the disease. Using in vitro and in vivo models of the Guillain–Barré syndrome variant, Miller Fisher syndrome, we have shown previously that anti‐GQ1b ganglioside antibodies target the presynaptic motor nerve terminal axon and surrounding perisynaptic Schwann cells, thereby mediating destructive injury through deposition of membrane attack complex. Here, we have used this model to investigate the effects of a novel therapeutic inhibitor of complement activation, APT070 ( Mirococept ), both in vitro and in vivo. In these models, APT070 completely prevents membrane attack complex formation, and thereby has a major neuroprotective effect at the nerve terminal, as assessed by immunohistology of perisynaptic Schwann cell and axonal integrity. These data provide a rationale for considering clinical trials of APT070 in Guillain–Barré syndrome, its variant forms, and other complement dependent neuromuscular disorders. Ann Neurol 2005;58:203–210