Human MiniPromoters for Brain Gene Therapy; Focused on Parkinson Disease

2016  -  Vancouver, BC,


The University of British Columbia

Project description

Gene therapy uses DNA to alter the behavior of cells to treat disease. There has been a promising revival of gene therapy for diseases with unmet treatment needs; including the approval of the first virus-based gene therapy by the U.S. Food and Drug Administration. Unfortunately, despite numerous clinical trials, neurodegenerative diseases of aging are not included in these gene therapy successes. One possible reason is that most gene therapies use unrestricted promoters (DNA control elements) that deliver the therapy to any cell, potentially causing unwanted side effects in healthy cells, and limiting the choice of therapies to less effective molecules.

The goal of this project is to develop a toolkit of human MiniPromoters (small DNA control elements) designed to delivery gene therapy only to restricted regions and cells in the brain. Thus, the project is a “pipeline” for promoter production, with four specific Aims to: 1) design computationally restricted MiniPromoters, 2) screen these promoters in mice, 3) further test them in mouse brains, and 4) test their usefulness in monkey brains. These MiniPromoters will be widely useful for many diseases of the brain, but are particularly focused on increasing the safety and efficacy of gene therapy for Parkinson Disease.

Relevance to the acceleration of therapeutics for neurodegenerative diseases of aging

The MiniPromoters are being developed in a way that maximizes their impact by optimizing their uptake by researchers interested in understanding and treating neurodegenerative diseases of aging. By creating our MiniPromoters for use in the smallest and thus most challenging gene therapy virus, we are ensuring they will be usable for a variety of additional therapeutic approaches. The preclinical monkey data will provide strong evidence of MiniPromoter applicability to humans. Patent protection will be sought for the most promising MiniPromoters to facilitate their “uptake” by companies. Finally, all MiniPromoters will be available to the research community through a non-profit distributor.

Anticipated outcome

The toolkit will include 30 MiniPromoters, fully characterized in mouse for cell-type restricted brain expression. The three most promising MiniPromoters for Parkinson Disease will also be fully characterized in the monkey brain. Thus, there MiniPromoters will be important new tools for gene therapy of Parkinson Disease. However, because of the similarity of cell types involved in many diseases of the brain, they may also be useful for neurodegenerative diseases such as Alzheimer Disease, and Huntington Disease. Overall, these MiniPromoters are expected to improve future clinical trial results significantly, by increasing gene therapy safety and efficacy, for neurodegenerative diseases of aging.