Complement inhibition abrogates nerve terminal injury in Miller Fisher syndrome
| Autor: | Peter D. Humphreys, Hugh J. Willison, Eric R. Wagner, Richard A. G. Smith, Susan Halstead, John A. Goodfellow |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Diagnostic Imaging
Male Diaphragm Neuromuscular Junction Schwann cell Motor nerve Complement Membrane Attack Complex In Vitro Techniques Pregnancy Proteins Complement C3c Mice Perisynaptic schwann cells Complement Inactivator Proteins Neurofilament Proteins medicine Animals Trauma Nervous System Axon Glycoproteins Mice Inbred BALB C Chi-Square Distribution Miller Fisher Syndrome Dose-Response Relationship Drug business.industry S100 Proteins Immunization Passive Immunohistochemistry Complement system Disease Models Animal medicine.anatomical_structure Neurology Neurology (clinical) business Complement membrane attack complex Neuroscience |
| Zdroj: | Annals of Neurology. 58:203-210 |
| ISSN: | 0364-5134 |
| DOI: | 10.1002/ana.20546 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text