Science
The science driving IBC's therapeutic approach
The perception of brain-immune interactions has dramatically changed over the past decade. Historically, any immune cell activity within the territory of the central nervous system (CNS), which includes the brain, the eye, and the spinal cord was considered a clear sign of pathology. The CNS was viewed as an autonomous unit, shielded behind barriers and nourished by the blood circulation.
In addition, it was commonly accepted that healthy brain function is optimally maintained when no immune cells are present. Until recently, this dogma was generally accepted, and the presence of immune cells in the CNS was viewed as exclusively detrimental, and as a negative outcome of blood-brain-barrier breakdown.
More than a decade ago, pioneering research from the laboratory of Prof. Michal Schwartz at the Weizmann Institute of Science in Israel demonstrated that functional maintenance of the brain requires a healthy immune system. Furthermore, recovery of the brain and spinal cord from acute injury requires the assistance of circulating immune cells, including monocyte-derived macrophages and regulatory T cells.
The association between the immune system and neurodegenerative diseases
Studying brain-immune interactions in Alzheimer's disease models, Schwartz’s group demonstrated that the peripheral immune system shows signs of dysfunction, reminiscent of accelerated aging, even prior to cognitive impairment. These changes in the immune response further perpetuate the disease. Blocking this negative feedback loop by targeting the PD-1/PD-L1 pathway, initiates an immune response in the periphery that drives the migration of specific immune cell populations to the brain, including anti-inflammatory T cells, and monocyte-derived macrophages that express unique scavenger molecules that allow removal of aggregated misfolded proteins, rescue synapses and protect neurons - collectively leading to restoration of brain function.
The effect was shown in different animal models of cognitive impairment, independent of disease etiology. In all tested models, PD-L1 blockade restored cognitive performance and prevented disease progression. The treatment affects both symptoms and disease pathology. Maintaining the long-term effect requires periodic treatment.
Based on these findings and IBC's wide IP portfolio, as well as additional supporting evidence from other research groups, IBC developed IBC-Ab002, a proprietary fully human anti-PD-L1 antibody designed to treat Alzheimer's disease and age-related dementia. IBC is also developing a pipeline of additional immune checkpoint treatments for other neurodegenerative diseases.