O1–03–02: In vivo targeting of antibody fragments to the nervous system for Alzheimer's disease immunotherapy and molecular imaging of amyloid plaques
Year: 2006
Type: article
Abstract: The ability to target therapeutic or diagnostic proteins to the nervous system is limited by the presence of the blood–brain/nerve barriers. We report that a monoclonal anti–fibrillar human Aβ42 immunoglobin (IgG4.1) or its F(ab')2 fragment (F(ab')24.1) that are polyamine modified have increased permeability at the blood–brain barrier. Both the native and modified F(ab')24.1 also showed increased binding to the antigen compared to the whole IgG as determined by ELISA. The F(ab')24.1 and polyamine modified F(ab')24.1 showed comparable in vitro binding to amyloid plaques in Alzheimer's disease (AD) transgenic mouse brain sections. Furthermore, intravenous injection in the AD transgenic mouse demonstrated efficient targeting to amyloid plaques throughout the brain. High–resolution emulsion autoradiography also demonstrated targeting of the radioiodinated polyamine–modified F(ab')24.1 to cerebrovascular amyloid deposits. Polyamine modification of this antibody derivative may have increased therapeutic potential for treating AD since exclusion of the Fc portion of the antibody should minimize the inflammatory response and cerebral hemorrhaging associated with passive immunization. Coupling contrast agents or appropriate radioisotopes to the polyamine–modified F(ab')24.1 might facilitate the molecular imaging of amyloid plaques using MRI or micro PET. While this approach has direct applications to AD, the efficient delivery of IgG fragments to the nervous system may have important applications to other neurodegenerative disorders or for the generalized targeting of nervous system antigens.
Source: Alzheimer s & Dementia
Institution: Mayo Clinic
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2052299232