Exogenous Peptidase for Amyloid-Beta Degradation

Current knowledge suggests that the development of age-related macular degeneration (AMD), a blinding disease that affects many older individuals, may involve the abnormally high build-up of a biochemical known as “amyloid-beta” in the eye. If abnormally high amyloid-beta promotes AMD, removing excess amyloid-beta could be a therapy for AMD. We plan to investigate an enzyme produced in many healthy tissues that acts to break down amyloid-beta. Using mice with AMD-like disease as our experimental system, we propose to study whether artificially increasing the amount of that enzyme in the eye can slow or block the progress of AMD.

Age-related macular degeneration (AMD) is a blinding disease that affects many older individuals. Current knowledge suggests that the abnormal build-up of a particular biochemical (a peptide), known as amyloid-beta, in the eye promotes the progression of AMD. We are working to develop a new and novel technology that can decrease the amount of amyloid-beta in eye tissues, and thus slow or block the onset of AMD. This new technology uses an enzyme, known as a peptidase, that attacks amyloid-beta and chemically inactivates it. In our experiments, we use mice that exhibit high levels of amyloid-beta in the eye, and we are investigating the ability of intra-ocularly delivered peptidase to decrease the level of amyloid-beta. Our project is specifically aimed at comparing two different methods of introducing the peptidase into the mouse eye.

The first of these is to access the target eye tissues by directly injecting small volumes of peptidase-containing solution into the vitreous compartment of the eye, in much the same way that certain drugs used in clinical ophthalmology are delivered to the eye. The second method is a gene therapy approach, the objective of which is to produce expression of the peptidase in the eye by delivering viral particles to the eye that carry the peptidase gene. Our research represents an important initial test of a new way to inhibit the build-up of excessive amyloid-beta in the eye and thereby delay or prevent AMD. Success in the project will set the stage for further development of this novel technology toward its application as a clinical therapy.