Abstract Details

Title Anti-C1q Therapy ANX005 Inhibits CSF Antibody-Driven Complement Activity Elevated in Early Stage Guillain-Barré Syndrome

Topic Autoimmune Neurology

Presentation(s) S25 - Autoimmune Neurology 2: Clinical Trials and Treatment (3:30 PM-3:42 PM)

Poster/Presentation
Number 001

Background

We hypothesize that in early GBS, classical complement-mediated peripheral nerve root damage and pathological changes in blood-CSF permeability allow detection of autoreactive antibodies and complement components in the CSF.

Objective

To determine the impact of intravenous ANX005 on the complement fixing ability of nerve-reactive IgM and IgG antibodies present in the cerebrospinal fluid (CSF) of patients with Guillain-Barré Syndrome (GBS).

Design/Methods CSF was collected from GBS patients participating in a randomized placebo-controlled phase 1b study, before and 5-12 days after intravenous administration of a single dose of ANX005 or placebo. CSF samples from 50 patients were screened for IgM and IgG antibodies against GM1 ganglioside, a known target of auto-reactive antibodies in GBS. Positive samples were examined for their ability to activate the classical complement cascade on plates coated with GM1 vs. control gangliosides, as measured by deposition of C3 and C4 on plates in an ex vivo assay. The assay relied on antibody and complement components already present within the CSF.

Results All GBS patients had elevated levels of immunoglobulin compared to control as well as complement proteins in their CSF (20-100x above controls), which correlated with the degree of blood-CSF barrier permeability measured by the CSF/serum quotient of albumin. IgG and IgM antibodies against GM1 were observed in 30% of patients, but not in CSF samples from patients. Pretreatment samples from the majority of these GBS patients triggered complement deposition specifically on GM1-coated plates, with the highest degree of activation in samples having both IgG and IgM anti-GM1 antibodies. In samples taken after treatment with ANX005, complement activation was inhibited compared to placebo, consistent with full engagement of C1q by the anti-C1q therapy.

Conclusions These findings support the hypothesis of IgG and IgM autoantibody-driven complement damage at the level of peripheral nerve roots, which is amenable to classical complement inhibition.

Authors/Disclosures
Henk-Andre A. Kroon, MD, MBA (Annexon Biosciences) PRESENTER	Dr. Kroon has received personal compensation for serving as an employee of Annexon Biosciences. Dr. Kroon has stock in Annexon Biosciences.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Zhahirul Islam	No disclosure on file
Ted Yednock, PhD (Annexon Biosciences)	Ted Yednock, PhD has received personal compensation for serving as an employee of Annexon Inc. Ted Yednock, PhD has received personal compensation in the range of $100,000-$499,999 for serving as an officer or member of the Board of Directors for Annexon Inc. Ted Yednock, PhD has received stock or an ownership interest from Annexon Inc. Ted Yednock, PhD has received intellectual property interests from a discovery or technology relating to health care.