Realizing the Dream Gene Therapy Program: Phase Two

<< Click here to read about phase one of the Realizing the Dream Gene Therapy Program

Below is a summary of the work to be funded by the FightSMA Realizing the Dream second campaign, in partnership with The Gwendolyn Strong Foundation. The work will take place in the Lorson Lab of the University of Missouri, by Dr. Monique Lorson and her colleagues.

Gene Therapy Links: Get in the Fight | A History of SMA Gene Therapy

Who is Dr. Monique Lorson?

Dr. Lorson

Dr. Monique Lorson attended St. Mary College where she received a Bachelor’s of Science Degree in 1990. In 1990, she was accepted into the Molecular Microbiology and Immunology graduate program at the University of Missouri, where she received her doctorate degree in 1996. While at MU, she studied cell cycle regulation and germline determination in the nematode C. elegans in the laboratory of Dr. Karen Bennett. A desire to understand more about how the loss of cell cycle regulation results in birth defects and cancer led to post-doctoral studies at Harvard Medical School and Massachusetts General Hospital Cancer Center under the direction of Dr. Sander van den Heuvel. After her postdoctoral studies she left scientific research for several years to have a family and she served as an instructor at Arizona State University. In 2003, she accepted a position as Assistant Research Professor in the Department of Veterinary Pathobiology at the University of Missouri. In 2003, Dr. Lorson received a two-year Reentry into Biomedical Careers award from NIH to study and begin research in SMA.

What is the goal of this phase of the campaign?
Our goal is to fund research for the generation of the first large SMA pre-clinical model.

Why does the SMA community need a large pre-clinical model?

  • It should more closely mimic the human condition
  • It will be closer to humans in size, physiology, metabolism, cardiac output, lung capacity, nervous system and immune system
  • Its intent is to expand the therapeutic window in order to identify the most effective therapeutics
  • It will provide a valuable resource for translational studies of two of the most promising SMA therapeutic strategies: 1) gene therapy to replace SMN and 2) oligonucleotide delivery to increase SMN2 exon 7 inclusion
  • It will facilitate the analysis of delivery methods, SMN expression, dosing, sustainability and immune response—all critical components for effective “bench to beside” (translational) applications

“Developing larger animal models for Spinal Muscular Atrophy is needed for research and therapeutic development in SMA. Currently, there are only tissue culture models of SMA and mouse models to screen drugs and therapies. The ability to test a therapy in a larger model of the disease can provide valuable data and provides a path towards translating to humans. Currently, there is no large model of SMA, so we perform safety and toxicology studies in normal animals. A larger model will give further efficacy and safety confidence in a drug or therapy. I applaud Fight SMA for the vision to support the SMA large animal model that is under development in Dr. Monique Lorson’s lab. We appreciate the FightSMA response to this pressing need. I am also very thankful for the FightSMA and Gwendolyn Strong Foundation funding our lab has received to date – funding that has allowed the initial safety and toxicity studies to be conducted. We are in the middle of these key studies, and so far, all looks good.”

Dr. Brian Kaspar, Nationwide Children’s Hospital, The Ohio State University

How long will it take?
Two years is the goal. More time will be required to generate all of the models that have different levels of SMN expression: from the most severe to milder forms of SMA.

Sometimes the challenge takes more refining and persistence. I have great confidence that the next two years are going to be very rewarding and full of accomplishments.”

Dr. Monique Lorson
University of Missouri

How did we arrive at this exciting juncture?
With funding from FightSMA and the National Institutes of Health (NIH), remarkable progress has been made. A preliminary model has been generated that should be an extremely valuable resource for developing and establishing efficacy in oligo-mediated therapies. The next venture is generating a true SMA model with two deleted copies of SMN.

The generation of an SMA model could never be realized without the vision and pioneering spirit of FightSMA. FightSMA saw the research potential and believed in the expertise of our research team. Thank you with extreme gratitude.

Dr. Monique Lorson

What will this cost?
This research requires $200,000 of funding for the two-year research period at the University of Missouri.