Advances in Antibody-Based Therapeutics for Cerebral Ischemia

Abstract

Cerebral ischemia is an acute disorder characterized by an abrupt reduction in blood flow that results in immediate deprivation of both glucose and oxygen. The main types of cerebral ischemia are ischemic and hemorrhagic stroke. When a stroke occurs, several signaling pathways are activated, comprising necrosis, apoptosis, and autophagy as well as glial activation and white matter injury, which leads to neuronal cell death. Current treatments for strokes include challenging mechanical thrombectomy or tissue plasminogen activator, which increase the danger of cerebral bleeding, brain edema, and cerebral damage, limiting their usage in clinical settings. Monoclonal antibody therapy has proven to be effective and safe in the treatment of a variety of neurological disorders. In contrast, the evidence for stroke therapy is minimal. Recently, Clone MTS510 antibody targeting toll-like receptor-4 (TLR4) protein, ASC06-IgG1 antibody targeting acid sensing ion channel-1a (ASIC1a) protein, Anti-GluN1 antibodies targeting N-methyl-D-aspartate (NMDA) receptor associated calcium influx, GSK249320 antibody targeting myelin-associated glycoprotein (MAG), anti-High Mobility Group Box-1 antibody targeting high mobility group box-1 (HMGB1) are currently under clinical trials for cerebral ischemia treatment. In this article, we review the current antibody-based pharmaceuticals for neurological diseases, the use of antibody drugs in stroke, strategies to improve the efficacy of antibody therapeutics in cerebral ischemia, and the recent advancement of antibody drugs in clinical practice. Overall, we highlight the need of enhancing blood–brain barrier (BBB) penetration for the improvement of antibody-based therapeutics in the brain, which could greatly enhance the antibody medications for cerebral ischemia in clinical practice.

Protection of Gueichih-Fuling-Wan on cerebral ischemia-induced brain injury in rodents is mediated by trans-cinnamaldehyde via inhibition of neuroinflammation and apoptosis

“…The availability of novel adjuvant neuroprotective tools may lead to a paradigm shift in stroke therapy [ 19 ]. Recent evidence has indicated that monoclonal antibodies targeting an endogenous molecule or signaling cascade would reduce the severity of the damaged brain tissue; however, the clinical evidence for stroke therapy is minimal [ 20 ]. Although monoclonal antibody therapy has proven effective and safe in treating various neurological disorders in animal studies, the complete antibody cannot cross the blood–brain barrier (BBB), and immunogenicity is a significant limitation [ 20 ].…”

“…Recent evidence has indicated that monoclonal antibodies targeting an endogenous molecule or signaling cascade would reduce the severity of the damaged brain tissue; however, the clinical evidence for stroke therapy is minimal [ 20 ]. Although monoclonal antibody therapy has proven effective and safe in treating various neurological disorders in animal studies, the complete antibody cannot cross the blood–brain barrier (BBB), and immunogenicity is a significant limitation [ 20 ]. Many studies are currently devoted to ascertaining safer and more effective therapies for ischemic stroke to meet clinical needs, and stem cell based ischemic stroke therapy is a current trend [ 21 ].…”

Development of a therapeutic monoclonal antibody against circulating adipocyte fatty acid binding protein to treat ischaemic stroke

“…In recent years, monoclonal antibody therapy is becoming more and more common for the treatment of various diseases such as cancers (Pento, 2017), autoimmune diseases (Arzoo et al, 2002) and neurological disorders (Sun et al, 2023), because of their better performance in terms of specificity, safety and pharmacokinetics, compared to small-molecule chemical drugs. Though a number of monoclonal antibodies were developed targeting signalling cascades and endogenous molecules modulating post-stroke inflammation, neuronal repair and regeneration, and showed beneficial effects in animal studies, none of them is approved for clinical use in stroke.…”