Abstract
Monoclonal antibodies (mAb) are promising therapeutics in multiple sclerosis and multiple new candidates have been developed, hence increasing the need for some agreement for preclinical mAb studies. We systematically analyzed publications of experimental autoimmune encephalomyelitis (EAE) studies showing effects of monoclonal antibodies. A PubMed search retrieved 570 records, out of which 122 studies with 253 experiments were eligible based on experimental design, number of animals and presentation of time courses of EAE scores. Analysis of EAE models, treatment schedules, single and total doses, routes of administration, and onset of treatment from pre-immunization up to 35 days after immunization revealed high heterogeneity. Total doses ranged from 0.1 to 360 mg/kg for observation times of up to 35 days after immunization. About half of experiments (142/253) used total doses of 10–70 mg/kg. Employing this range, we tested anti-Itga4 as a reference mAb at varying schedules and got no, mild or substantial EAE-score reductions, depending on the mouse strain and onset of the treatment. The result agrees with the range of outcomes achieved in 10 reported anti-Itga4 experiments. Studies comparing low and high doses of various mAbs or early vs. late onset of treatment did not reveal dose-effect or timing-effect associations, with a tendency towards better outcomes with preventive treatments starting within the first week after immunization. The systematic comparison allows for extraction of some “common” design characteristics, which may be helpful to further assess the efficacy of mAbs and role of specific targets in preclinical models of multiple sclerosis.
Highlights
Monoclonal antibodies are increasingly used and developed as therapeutics in multiple sclerosis (MS)
Prominent candidates are natalizumab targeting α-4 integrin and two “old” antibodies against lymphocyte surface markers, alemtuzumab (CD52) and rituximab (CD20), which have been repurposed for multiple sclerosis, and the recently from the U.S Food and Drug Administration (FDA)-approved ocrelizumab, targeting the B-cell antigen, CD20 and is the first for relapsing remitting (RRMS) and primary progressive forms of MS (PPMS) [1,2]
MAbs are second line drugs for escalation therapy mostly for relapsing-remitting MS, but the success strongly suggests that Monoclonal antibodies (mAb) targeting immune cell subtypes, surface antigens or their ability to penetrate the blood brain barrier interfere with the autoimmune attack that leads to a destruction of the myelin sheaths in MS
Summary
Monoclonal antibodies are increasingly used and developed as therapeutics in multiple sclerosis (MS). Prominent candidates are natalizumab targeting α-4 integrin and two “old” antibodies against lymphocyte surface markers, alemtuzumab (CD52) and rituximab (CD20), which have been repurposed for multiple sclerosis, and the recently from the U.S Food and Drug Administration (FDA)-approved ocrelizumab, targeting the B-cell antigen, CD20 and is the first for relapsing remitting (RRMS) and primary progressive forms of MS (PPMS) [1,2] The success with these monoclonals in MS has raised the scientific and pharmaceutical interest to develop additional, better or less problematic mAbs, and several new candidates are being tested in phase-2 or -3 clinical trials. A number of targets are being evaluated, in particular CD40 [7,8] and its ligand and other tumor necrosis factor (TNF) family members [9,10,11] and antibodies targeting IL-12 [12], IL-17 [13] or IL-21 [14]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
