A newly designed antibody transport vehicle targeting the transferrine receiver allows an improvement in the delivery of anti-amyloid antibodies to the brain of mouse models from Alzheimer’s disease, researchers report. According to the study, the approach preserves key immune functions, such as the microglial clearance of plates, while offering a safer and more effective administration strategy for anti-amyloid immunotherapy.
Alzheimer’s (AD) disease is marked by the accumulation of amyloid-β (Aβ) protein plates in the brain. Anti-amyloid drugs approved by the FDA, such as Adducanumab, Lecanemab and Donanemab, have shown a success limited to reducing the accumulation of Aβ plaque and a slightly slowed cognitive decline. However, they do not prevent the disease from progressing. Their clinical advantages could be more limited by sub-optimal penetration into the brain and by current side effects, in particular the swelling of the brain and small brain bleeding, collectively called imagery anomalies linked to the amyloid (ARIA).
To overcome these limitations, Michelle Pizzo and her colleagues have designed a new antibody transport vehicle (mountain bike) which targets the transferrine receiver – a natural gateway on the blood vessels which allows certain molecules to cross the BBB. Design, called mountain bikesEmperorIncludes a mutation to reduce harmful interactions with immune receptors on immature red blood cells, thus preventing cytotoxic side effects. In an ad mouse model, pizzo et al. Show this, when merged with an anti-amyloid-β antibody (creating a mountain bikeCislala:Aβ), modified therapy has successfully entered cerebral tissues more effectively than conventional antibodies.
In particular, mountain bikingCislala:Aβ was widely distributed throughout the brain parenchyma, increasing the brain concentrations from five to eight. The researchers’ approach has also shown increased targeting of Aβ associated with the plate in the brain fabric rather than in blood vessels, which has reduced vascular inflammation and considerably reduced the incidence of ARIA side effects. “Taken together, the results of the pizzo et al. Provide proof of more than preclinical concept; They also establish a therapeutic design framework, “write Mengen Xing and Weihong Song from a related perspective”.Emperor: Aβ overcomes the long -standing limits of AD immunotherapy.