Publication Date

2019-04-18

Availability

Open access

Embargo Period

2019-04-18

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PHD)

Department

Biochemistry and Molecular Biology (Medicine)

Date of Defense

2019-03-19

First Committee Member

Sanjoy Bhattacharya

Second Committee Member

Zafar Nawaz

Third Committee Member

Feng Gong

Fourth Committee Member

Michal Toborek

Fifth Committee Member

Ralf Landgraft

Sixth Committee Member

Gerold Feuer

Abstract

Despite significant resource expenditures and decades of focused research, chronic age-associated diseases have not been met with improvements in patient outcomes that reflect the successes against infectious disease over the last century. This observation calls into question contention approaches to drug discovery for diseases of aging, and more importantly, their molecular targets. Herein, the strategies for engineered negligible senescence (SENS) framework for drug discovery -- an approach to treating aging broadly based on damage mitigation -- is presented. A translational program for age-related macular degeneration is detailed as illustration of this approach. Collectively, this work validates the academic and commercial viability of the SENS damage repair platform and presents a novel therapeutic modality that may eventually treat the global leading cause of vision loss in the elderly.

Keywords

macular degeneration; sens; Stargardt; enzyme replacement therapy

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