Funding the Next Generation

2022 accelerators Prize Finalists

Leonard Burg

Leonard Burg, PhD

Children’s Hospital
of Philadelphia

Identifying therapeutic leads to
treating Leigh Syndrome
in Zebra Fish

Project Summary
Mitochondria are critical cellular components that are responsible for generation of roughly 90% of a person’s biochemical energy, defects in which result in a broad class of disorders known as mitochondrial disease. Leigh syndrome is an early childhood-onset, progressive neurodegenerative disorder with high morbidity and mortality that occurs in approximately 1 in 40,000 individuals. Leigh syndrome is caused by mutations in one of more than 95 genes that impair mitochondrial energy production – one of the most common gene mutations occurs in SURF1. Our lab has generated two surf1 zebrafish mutant models that mimic symptoms of human Leigh syndrome patients. These zebrafish models exhibit stroke-like brain cell death; however, the mechanism of this cell death is unknown. Identification of the specific cell death mechanism in these models may provide new targets and treatment options to prevent the brain cell death. This study proposes to identify novel therapeutic leads by determining the mechanism of cell death in the brain and by screening an FDA approved compound library in these zebrafish models of human Leigh syndrome.
Sara Carli

Sara Carli, PhD

Università di
Bologna, Italy

Pre-clinical study on
novel treatment strategies
for RRM2B disease

Project Summary

Mitochondria have their own genetic material, the mitochondrial DNA (mtDNA). Having too little mtDNA is one of the causes that drives the onset of Mitochondrial Depletion Syndromes (MDSs). Patients with MDS experience a spectrum of symptoms which generally lead to death in a few months. mtDNA depletion could be due to a defect in the production of a primary building block or gene of the mitochondrial DNA. Currently, there are no animal models present to better understand MDS or to test the effectiveness of therapeutic treatments. This project proposes to create a mouse model that will be used to better understand the progression of MDS. With a mouse model available I will then test the effectiveness of gene therapy, an innovative therapeutic approach to restoring the defective gene that causes MDS. 

Filomena Massa

Filomena Massa, PhD

Fondazione Telethon, Telethon Institute of Genetics and Medicine (TIGEM)

Generation of innovative gene-independent therapeutic strategies for mitochondrial optic neuropathies (MONs)

Project Summary
Mitochondrial optic neuropathies, also called MONs, are a group of rare disorders characterized by the deterioration of the retina which causes reduced vision or blindness. The most common forms of MONs are Autosomal Dominant Optic Atrophy (ADOA) and Leber Hereditary Optic Neuropathy (LHON). The complexity of MONs presents significant limitations to the application of conventional gene therapy. Thus, we hypothesize that focusing on the turnover of mitochondria through the selective degradation of mitochondria and the synthesis of new mitochondria, may represent an alternative therapy. We have identified two small RNA molecules, when inhibited, are key in protecting retinal calls.  I propose to evaluate the therapeutic efficacy of the inhibition of these two molecules in models of ADOA. I will also perform a drugs screening in MONs cell lines, in order to identify new drugs able to increase mitochondria turnover. If successful, this project may lead to the development of new therapeutic strategies for the treatment of these disorders.
Become an accelerator

Your Involvement Matters

Innovation, speed and agility are key to finding effective treatments for mitochondrial disease.  Your support is the beginning.  Accelerating the research could lead to a cure.

Our accelerators are engaged philanthropists.  Through our annual livestream-pitch event, our members have the opportunity to cast their vote for the project they feel the most passionate about, and ultimately see the difference their contribution makes.

How It Works

UMDF earmarks the accelerators 
prize
($50,000 in 2022)

h

Grant applications submitted by promising post-doctoral fellows

 

Applications reviewed and finalists selected by UMDF Scientific and Medical Advisory Board

3-5 finalists prepare “fast pitches” to be broadcast live at UMDF Symposium

 

Z

Each accelerator 
casts a vote for the project they feel most passionate about

Prize awarded to winner

Right now… a researcher in a lab believes her theory could cure mitochondrial myopathy.

Right now… a scientist believes his innovation may bring about an end to Leigh syndrome.

Right now… people affected by mitochondrial disease need energy…and YOUR energy can help….but we need to go fast.

It could be an innovation that will find the cause of mitochondrial disease. Or, it may be the research that develops an effective treatment. Now is the time to accelerate that science from bench to bedside. Our patients and families are counting on your energy to help UMDF move faster toward a cure.

When you give $500 or more (cumulatively in a year), you unlock your accelerators benefits! No matter how you give – through a special event, to a designated fund or as a tribute to a patient – when you reach the accelerators level you join a group of engaged philanthropists. You will get a first-hand look at the promising ideas being developed in mitochondrial disease research.

In addition to the opportunity to jumpstart discovery for the next generation of mitochondrial disease researchers, our accelerators receive: 

  • Name recognition at the annual Symposium
  • accelerators lapel pin
  • accelerators social media badge

2021 Prize Winner

Lia Mayorga, MD, PhD

IHEM
Mendoza, Argentina

Project Summary
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.

2020 Prize Winner

Kinsley Christopher Belle

Stanford University
Stanford, CA

Project Summary
Mutations in mitochondrial DNA result in an array of disease which can be found in nearly all tissue types of the human body. Furthermore, these mutations can exist in varying states of prevalence due to a rare phenomenon known as heteroplasmy. Heteroplasmy is the percentage of mutant mitochondrial DNA within a cell, tissue, or organ system.  The level of heteroplasmy or the percentage of mutation directly correlates with disease and cellular dysfunction. 

Our objective is to determine how internal factors, such as development and cell specification cues, as well as external stimulus, oxygen levels, energy substrates, and drug compounds influence mitochondria heteroplasmy. Our preliminary assessments suggest that cell-type development and cell division influence heteroplasmy in developing tissues, additionally our work on cell conditions, and small molecules has yielded promising preliminary results for possible therapeutics. This body of work serves as a template for discovering compounds that reduce mitochondrial heteroplasmy and thus disease burden in patients.

2019 Prize Winner

Arwen Gao

Ecole Polytechnique Federale de Lausanne (EPFL)
Lausanne, Switzerland

Project Summary
Dr. Gao was awarded a $50,000 prize for her project entitled Identification of Novel Compounds to Treat Rare Mitochondrial Diseases. The goal of this research project is to identify novel compounds that increase the amount of mitochondria and/or activate the identified pathway in lab-based cell models. The compounds that work best in the cell models will be subsequently tested in animal models of mitochondrial disease. Future work with top compound candidates have the potential to pave the way towards the development of novel drugs targeting rare mitochondrial diseases.

Scientists who are working fast toward a cure.

Vamsi K. Mootha, PhD

HARVARD MEDICAL SCHOOL • Boston, MA

“In 2004, I was a recipient of a $90,200 UMDF grant designed to support my efforts on using computational genomics to identify novel assembly factors for mitochondrial oxidative phosphorylation. With this support, I was able to recruit and hire a talented computational biologist, who proceeded to predict the mitochondrial proteome using a computational tool that led to the identification of several new disease genes, forming the basis for my lab’s first NIH grant.”

Anna-Kaisa Niemi MD, PhD

RADY CHILDREN’S HOSPITAL • San Diego, CA

“A UMDF Clinical Fellowship Award allowed me to focus on diagnosis and treatment of patients with confirmed or suspected mitochondrial disorders. The most impactful part of the fellowship for me was learning about the daily life of children and families affected by mitochondrial disorders. I now continue to use the knowledge and experience I gained that year in my work caring for critically ill infants with confirmed or suspected mitochondrial disorders.”

Michael J. Palladino, PhD

UNIVERSITY OF PITTSBURGH • Pittsburgh, PA

“In 2006, I received a $98,000 research grant from UMDF. This grant funded my research to further develop our Drosophila NARP/MILS model and allow our first venture into compound screening to identify specific drug therapies for mito patients. This award served as “bootstrap funding” helping me successfully apply to the NIH for support of numerous projects and helped secure more than $2.75M in NIH funding for mito research in my lab.”

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