Detection and Treatment of Alzheimer's Disease and Other CNS Diseases

Technology #2003-149

Technology Description
Compositions and methods have been developed for detecting plaques and treating CNS disorders. Polyamine modification of amyloid beta peptides or antibodies binding to amyloid beta increases blood-brain barrier (BBB) permeability and incorporation of a contrast agent permits MRI detection of plaque deposits. A novel peptide-based imaging agent has also been developed based upon incorporation of particular chemically synthesized amino acid compositions. Incorporation of these residues facilitates BBB permeability of amyloid beta peptides and antibodies, and labeling with an imaging agent permits diagnostic interpretation.

Advantages
The capability to diagnose and potentially treat Alzheimer’s and other CNS diseases, facilitated by the increased blood-brain barrier permeability of peptides and antibodies.

Stage of Development
Extensive mouse studies have been conducted examining the diagnostic efficacy of these agents, their blood-brain barrier permeability, and their pharmacokinetics.

References
Poduslo et al. Molecular targeting of Alzheimer’s amyloid plaques for contrast-enhanced magnetic resonance imaging. Neurobiol Dis 2002;11(2):315-29.
Poduslo et al. Design and chemical synthesis of a magnetic resonance contrast agent with enhanced in vitro binding, high blood-brain barrier permeability, and in vivo targeting to Alzheimer’s disease amyloid plaques. Biochemistry 2004;43(20):6064-75.
Poduslo et al. In vivo targeting of antibody fragments to the nervous system for Alzheimer’s disease immunotherapy and molecular imaging of amyloid plaques. J Neurochem 2007;102(2):420-33.
Kandimalla et al. Pharmacokinetics and amyloid plaque targeting ability of a novel peptide-based magnetic resonance contrast agent in wild-type and Alzheimer’s disease transgenic mice. J Pharmacol Exp Ther 2007;322(2):541-9.
Ramakrishnan et al. Surface plasmon resonance binding kinetics of Alzheimer’s disease amyloid beta peptide-capturing and plaque-binding monoclonal antibodies. Biochemistry 2009;48(43);10405-15.