Antibodies against Alzheimer’s dementia
ISAR Bioscience develops novel antibodies directed against a protein relevant for Alzheimer’s disease. First results are encouraging.
New drugs for the treatment of Alzheimer’s disease are urgently needed. Some antibodies have recently been introduced into therapy, but so far they have shown only minor effects and only in the early stages of the disease.
ISAR Bioscience is developing novel antibodies against a target protein found on microglia cells in the brain that mediates their activation, the “human triggering receptor expressed on myeloid cells 2” (hTREM2). This protein is genetically associated with Alzheimer’s disease, and several anti-TREM2 antibodies are currently being investigated in clinical trials worldwide. However, all of these anti-hTREM2 antibodies originate from animal immune systems and have only subsequently been humanized.
In contrast, the antibodies against hTREM2 that are being developed by ISAR Bioscience are fully human, monoclonal antibodies that specifically target the brain. The prototype antibody M07-TFN shows higher binding affinity and stronger activation of hTREM2 than all previously described anti-hTREM2 antibodies. M07-TFN improves the vitality of microglia cells and shows good transfer in blood-brain barrier (BBB) models. In preclinical Alzheimer’s models in vivo, M07-TFN improves attention, spatial orientation, and memory and significantly reduces amyloid plaque load. Safety studies showed no adverse effects on blood cells or major organs.
In summary, M07-TFN has the best affinity and efficacy in its class compared to other antibodies currently in development. As it is a fully human anti-hTREM2 antibody, it promises lower immunogenicity when used in patients.
Patent
Christlmeier MA, Kraller M, Simmnacher K, Holthoff HP, Ungerer M (2024) Human anti-TREM2 antibody for treating neurodegenerative disorders. Patent application WO 2024-160736 A1
