Innovation, speed and agility are key to finding effective treatments for mitochondrial disease and accelerating the research could lead to a cure. That is why each year, the UMDF awards the accelerators prize to a promising Postdoctoral Fellow whose research project was selected by the UMDF Scientific and Medical Advisory Board as a finalist for the award.
Each finalist will present their project during the Big Pitch broadcast during the UMDF Mitochondrial Medicine Symposium at 12:00 PM EDT on Friday, June 25, 2021.
After the Big Pitch broadcast, donors, who qualify as accelerators, vote on the project they feel most passionate about. The project receiving the most votes is the 2021 accelerators Prize Winner.
Here are the 2021 accelerators Prize finalists:
Lia Mayorga, MD, PhD
Title: Modulation of the nuclear epigenome as a new strategy for mitochondrial DNA heteroplasmy shift
Human cells have two types of DNA, nuclear and mitochondrial DNA. The latter controls energy production for the body which is essential for life. Each cell has many mitochondria to generate sufficient energy for our organs, and inside each mitochondrion, there are many copies of mitochondrial DNA. In patients with certain types of mitochondrial diseases, the mitochondrial DNA copies are not identical, resulting in a mixture of defective and normal copies. The defective copies lead to poor mitochondrial function and disease, so the more defective vs. normal copies a cell has, the worse the disease symptoms. Our goal is to develop a method to selectively reduce the number of defective mitochondrial DNA copies, leaving mostly normal ones. Gene therapy strategies that have worked for nuclear DNA defects have not reached clinical trials for mitochondrial genes because the mitochondrion is very selective as to what can or cannot enter the organelle. We propose a different approach taking advantage of the cell’s natural communication between the nucleus and mitochondria. Previous work has shown that intense mitochondrial dysfunction, such as the one present in cells with mostly defective mitochondrial DNA, produces modifications to nuclear DNA (not in sequence, but in function) that perpetuate the survival of such unhealthy cells and sustain disease symptoms. Consequently, we plan to modify these nuclear DNA modifications that exist in dysfunctional cells to “select” cells with the less defective mitochondrial function. This nuclear DNA modulation technique is already used to treat other illnesses, which increases the possibility for it to reach clinical trials in less time.
Michela Di Nottia, PhD
Bambino Gesù Children’s Hospital
Title: The role of inflammation in diseases related to mitochondrial DNA maintenance: new potential biomarkers to be used as therapeutic targets
Mitochondrial diseases (MDs) are considered the most common inborn errors of metabolism causing a dysfunction in the energy production. The integrity of mitochondrial DNA (mtDNA) is important in producing healthy mitochondria, which is essential in the maintenance of cellular health. Damage to the mtDNA can induce a pro-inflammatory state in the cell. No studies to date, have addressed the link between innate immune response and mitochondrial function in primary mitochondrial diseases. My study proposes to explore the effect of mtDNA instability on inflammation and the clinical impact it has on affected patients. We will start studying Kearns-Sayre patients which are characterized by a single mtDNA deletion. We will evaluate inflammatory biomarkers in all tissue available (blood, muscle biopsy and cultured fibroblasts) and test the effects of appropriate drugs.
With this project we intend to elucidate novel relevant pathogenic pathways and to identify new potential biomarkers and therapeutic strategies to be tested in controlled clinical trials. Moreover, the results herein obtained will pave the way for the evaluation of the inflammatory status in other mitochondrial diseases, for which an early treatment could improve the clinical picture.
John Smolka, PhD
University of California
Title: Establishing roles for the mitochondrial tRNA biosynthetic machinery in mitochondrial genome maintenance
Mitochondria, the engines of our cells, contain their own small DNA blueprint, the mitochondrial genome, with genetic instructions important for our metabolism. Furthermore, our cells have to make hundreds to thousands of copies of the mitochondrial genome for normal health. Compared to our knowledge of how cells copy and pass on our non-mitochondrial DNA from cell to cell and parent to child, the mitochondrial DNA copying process, or mitochondrial DNA replication, is poorly understood. I am working to fully understand all the parts of the cellular machine that replicates mitochondrial DNA, and how they work. By reverse engineering the mitochondrial DNA replication machine, my work is uncovering the possibility that the genetic mutations that cause Mitochondrial Encephalopathy, Lactic-Acidosis and Stroke-like episodes (MELAS) do so by interfering with the mitochondrial DNA copying process. You cannot repair an engine unless you know how it works, and this fundamental knowledge has the potential to inform future therapeutic strategies for treating mitochondrial diseases that arise from MELAS-causing mutations and defects in mitochondrial DNA replication.
Watch these accelerators Prize finalists present their projects on Friday, June 25, 2021 at 12:00PM EDT.