The Logan Sloane Aronson Research Fund in honor of Sydney Breslow
Sydney Breslow was diagnosed with an unspecified mitochondrial disorder when she was eight years old after years of medical testing to determine the cause of her physical difficulties. Her specific mitochondrial disorder affects her neurologically, which causes difficulties with her balance, vision, speech and walking, presenting a myriad of daily challenges.
In 2016, due to advances in genetic testing, Sydney’s mitochondrial disorder was identified as MEPAN, which is caused by a mutation in the MECR gene. This condition often worsens over time and there is currently no cure available.
Despite these challenges, Sydney graduated Summa Cum Laude from High Point University in May of 2015 with a BA in Special Education. In December of 2016, Sydney received her Masters Degree in Special Education with a concentration in Intellectual Disabilities also from High Point University. She currently works as the Disability Services Coordinator at Jewish Family and Children Services of Southern New Jersey. Sydney is passionate about helping people with disabilities reach their full potential.
Sydney is dedicated to raising awareness and funds for the United Mitochondrial Disease Foundation, hoping that one day there will be a cure for this debilitating, devastating, and many times fatal disease.
On November 29, 2013, the day after Thanksgiving, Sydney and her family tragically lost their nephew and cousin, Logan Aronson.
Logan was an amazing young man who was interested in international business and had a great love of history. He was known for his common sense, street smarts and good nature. Wherever he was, his quick wit and great sense of humor drew people to him.
Admirably, Logan uniquely danced to the beat of his own drum and was true to himself and his ideals. Logan was an inspiration to all in the way he loved life, his family and friends. Determined to turn this loss into something positive, Logan’s parents, Debra and Ron, requested a research fund be established with the United Mitochondrial Disease Foundation in memory of Logan and in honor of Sydney.
Nothing would have made Logan happier than to help Sydney and others with mitochondrial disorders.
Upcoming Fundraisers
Learn about how you can support The Logan Sloane Aronson Research Fund in honor of Sydney Breslow via Cousins for a Cure.
Investments
Since June 2019: The Logan Sloane Aronson in Honor of Sydney Breslow Research Fund invested $825,000 toward:
$650,000 toward:
Deborah Murdock, Ph.D.,
Principal Investigator
Children’s Hospital of Philadelphia
Philadelphia, PA
Phase 1 – $200,000 (September 2019)
Phase 2 – $450,000 (November 2023)
Development of Therapeutic Models for MECR-Related Disease
Specific Aim 1: Characterize the levels and identities of the bioactive lipids (acyl amides) made by the mtFASII pathway in established cell lines. Genetic modifications will be made to a cultured cell line to up- and down-regulate the mtFASII pathway. Untargeted metabolomics will be used to characterize the levels and the specific identity of the lipid molecules.
Specific Aim 2: Create a neuronal cell model of MECR deficiency. Fibroblasts from patients with MECR-related disease will be converted into induced pluripotent stem cells (iPSCs). These iPSCs will be transformed into a neural cell line by forced expression of neurogenin. Untargeted metabolomics will be used to determine which of these bioactive lipids are altered in neuronal cells made from fibroblasts from patients with MECR deficiency (MEPAN syndrome). We will then determine if addition of the missing molecules will restore the cells to normal function.
Updates on MEPAN progress 8/28/2023
Center for Mitochondrial and Epigenomic Medicine
Children’s Hospital of Philadelphia
On July 1, 2023, Mecr and MEPAN were the focus of a session of the UMDF’s Mitochondrial Medicine Symposium in Charlotte, NC chaired by Dr. Deborah Murdock.
At the UMDF meeting, Dr. Murdock presented what we have learned so far from studies on our mouse models of MEPAN. The MEPAN mouse has a movement disorder and an eye disorder with a normal life span, making it an excellent model for studying MEPAN and testing therapies. Studies on the brain of the MEPAN mouse show that it has difficulty making energy in a specific part of the brain responsible for balance and movement, the cerebellum. We have discovered that part of the machinery required to make energy is put together incorrectly in the mitochondria of the cerebellum. Understanding how this machinery has gone wrong helps tremendously in developing ways to fight the disease. We have also discovered that the MEPAN mouse has an altered stimulation of the immune system in the brain. Therapeutics aimed at treating the immune system and strategies using stem cells and mitochondrial transfer as therapies are planned in phase II of this work.
The UMDF meeting, organized by CMEM’s Dr. Douglas Wallace, and Dr. Murdock, also included focus areas on mitochondria and the immune system, mitochondria and viruses, and mitochondrial transfer. Several scientists presented the results of their latest research on how Mecr functions in the mitochondria. Families, scientists, genetic counselors, and physicians gathered after the session for a more extensive interaction about MEPAN. This meeting was the first of many and we hope that these interactions will foster a better understanding of MEPAN and the development of therapeutics, in addition to spreading awareness about MEPAN among the mitochondrial disease community.
Updates on Phase II of Developing Therapeutics for MEPAN
Center for Mitochondrial and Epigenomic Medicine
Children’s Hospital of Philadelphia
Understanding MEPAN through the mouse model
Great progress has been made in our understanding of the disease mechanics of MEPAN through our studies of the mouse model of MEPAN. Iron is a fundamental player in energy production in all mitochondria in the form of iron-sulfur clusters. When iron is free in the cell, it interacts with oxygen to create toxic free radicals that damage protein and lipids, eventually causing cell death. In MEPAN, these iron-sulfur cluster are made incorrectly, causing energy deficits in the brain and toxic iron byproducts. This is very similar to the disease mechanics in Friedreich’s ataxia (FA), the most common inherited ataxia (occurring in 1/50,000 people in the US). The similarities between FA and MEPAN allow us to use what has been learned in the last 30 years of research on FA, much of it performed by our colleagues here at CHOP and University of Pennsylvania, to inform our choice and testing of drugs for MEPAN.
MECR gene therapy progress
In a collaboration between scientific institutes (Center for Mitochondrial and Epigenomic Medicine at the Childrens Hospital of Philadelphia and Powell Gene Therapy Center at the University of Florida) and family impact funds within UMDF (The Logan Sloane Aronson Research Fund For Mitochondrial Disease in Honor of Sydney Breslow and Solomon Family and Friends Impact Fund) we have made progress in our efforts towards a gene therapy for MEPAN. Gene therapy targets the main initiator in genetic disease, the mutant gene. Adeno-associated virus (AAV)-based vectors have been created that transfer and express a normal copy of MECR in the neonatal mouse brain, paving the way for testing of these vectors in the MEPAN mice.
Mitochondrial transfer and cellular therapy
An alternate method to treat mitochondrial diseases involves the transfer of healthy mitochondria or cells to the diseased tissue. We are testing both types of transfer in the MEPAN mouse model. Neural stem cells can be grown in the lab, and then transplanted into animals where they engraft and can differentiate into other cell types. Neural stem cells also secrete extracellular vesicles, many of which contain packaged mitochondria that can be transferred to other cells. We have created neural stem cells from mice that have their mitochondria tagged with a fluorescent protein, allowing us to track mitochondrial transfer. We are growing these cells in the lab, and establishing the technology needed to engraft these cells or their mitochondria in the MEPAN mice.
Photograph of Neurosphere from Healthy Mouse.
This neurosphere was cultured from a healthy lab mouse and consists of approximately 10,000 neural stem cells which can be differentiated into neurons, astrocytes, or oligodendrocytes. Its mitochondria contain a red fluorescent protein, allowing these mitochondria to be traced in the engrafted brain.
$175,000 toward accelerators –
Rachel Guerra
Morgridge Institute for Research
Madison, WI
Accelerator Project: Structural and Functional Characterization of COQ9 in Facilitating Coenzyme Q Biosynthesis and Complex Q Formation
Zachary Wilson
University of Utah
Salt Lake City, UT
Accelerator Project: Manipulating Mitochondrial Metabolism Via The Mitochondrial Derived Compartment Pathway
June 2020:
Kinsley Bell
Stanford University
Stanford, CA
Accelerator Project: Investigating intrinsic and extrinsic factors influencing mitochondrial heteroplasmy
in mt-tRNA mutation-linked disease
June 2023:
Jonathan Deitz, PhD
Rutgers University
Accelerator Project: The Role of Metaxins in Mitochondrial Health and Homeostasis
June 2024:
Daniel Lagos, PhD
University of Cambridge
Accelerator Project: Unveiling the Role of Secreted Mitochondria in Extracellular Vesicles: Implications for Primary Mitochondrial Disease
MitoMed Scholarships 2026
Thanks to scholarships funded by The Logan Sloane Aronson Research Fund for Mitochondrial Disease in Honor of Sydney Breslow, five up-and-coming researchers interested in the mitochondrial disease field were able to attend UMDF’s Mitochondrial Medicine Conference 2026 in Orlando, FL. More than $8,000 in awards were issued, including registration and travel.
Each year, Mitochondrial Medicine Conference brings together the best minds in mitochondrial medicine and the patients they serve. In 2026, more than 600 people – representing 36 states and 14 different countries, attended. For the science and medical community, the conference provides an international stage for leaders to inspire the next generation of researchers. Attendees learn about the latest developments in the field of mitochondrial medicine, including industry advancements, potential treatments, therapies and cutting-edge research. The event also gives the scientific communities the unique experience of engaging with affected patients to better understand symptoms and work faster towards a cure.
Congratulations to the following researchers. We look forward to following your careers!
Shirin Parvin , Iowa State University
Madhurima Saha, University of Florida
Mouna Trabelsi, Medical University of South Carolina
Tarun Yadav, University of Utah
Zhantao Zhu, Iowa State University
Video Library
Update from the 2019 accelerator winner, Dr. Arwen Gao
UMDF’s 2020 accelerator winner, Dr. Kinsley Bell
Cousins for a Cure Video Library
Watch 2023 Cousins for a Cure virtual event
https://vimeo.com/885305423?fl=pl&fe=sh
Watch 2021 Cousins for a Cure virtual event.
https://vimeo.com/647375092?fl=pl&fe=sh
Join UMDF as they catch up with Alan Breslow and the annual Cousins for a Cure event.
Powerhouse Podcast Episode #10: Cousins for a Cure – YouTube
The Case for Investing in Mitochondrial Disease Research – Dr. Phil Yeske, UMDF Science and Alliance Officer.
The Case for Investing in Mitochondrial Disease Research
Alan Breslow on UMDF’s 25th Anniversary.
UMDF 25th Anniversary: Alan Breslow