Ten years ago, a University of Minnesota pediatric bone marrow transplant team successfully treated two patients with epidermolysis bullosa — a fatal skin disorder where children suffer from painful blisters and lesions — by providing them with new cells that could improve their skin. The procedure held big implications for the medical world.
“It was the first time anyone was able to show you can fix the problem of one organ with stem cells from a different organ,” said Jakub Tolar, a doctor from the original bone marrow team and director of the U’s Stem Cell Institute. The method changed the field of regenerative medicine. Now Tolar is working with genome editing expert Dr. Mark Osborn, an assistant professor with the U’s Department of Pediatrics. Together, Tolar and Osborn have taken this gene therapy a step further.
Tolar will present their work on a new type of gene editing that allows scientists to replace a problematic gene, but with fewer side effects, at the upcoming Life Sciences Innovation Showcase on May 20. The event brings together leading medical innovators from the U of M and Mayo Clinic to display their latest developments in cutting-edge medical technology.
Osborn and Tolar’s work targets two very different diseases: epidermolysis bullosa and Fanconi anemia. Epidermolysis bullosa, also called EB, is a genetic disorder that results from a lack of a critical protein that binds the layers of skin together. Without the protein, skin slides apart, blisters, and shears off, leading to severe pain, disfigurement and premature death, often from skin cancer. Fanconi anemia, on the other hand, is a syndrome where bone marrow fails to produce new blood cells, leading to infections, bleeding, shortness of breath and sometimes death. While the two diseases are different, both are caused by a faulty gene, making them good candidates for gene therapy.
While gene therapy has been in use for years, previous methods have always employed a virus as the gene delivery system; this may cause complications in the body that could be as severe as leukemia, a type of blood cancer. Dr. Osborn’s research has focused on new, non-viral genome editing techniques. After years of researching different methods, Tolar and Osborn believe they can now remove one specific “letter” from a vast genetic code and replace it with another, all without altering other parts of the code or using a potentially harmful virus. This is a customized treatment, where a specific patient’s cells are taken, the flawed gene strand is edited, enough corrected cells are grown, and these are returned to the same patient. Over time, these cells grow in the patient’s body and function normally, which, hopefully, results in a permanent cure for the patient’s condition.
Dr. Jakub Tolar (Photo by Scott Streble)
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“Everything we know about this procedure tells us it’s going to be less problematic than the previous version of gene therapy,” Tolar said, adding the procedure could mean patients suffering from diseases like epidermolysis bullosa will have better treatment options with fewer harmful side effects.
The U’s Office for Technology Commercialization has helped Tolar patent the concept, which will next move to the clinical trial stage. If it succeeds, it will be the first time in history that scientists have used cells custom-engineered to fit a specific patient.
A promising future for gene editing treatments
Tolar and Osborn’s work is a convergence of expertise from several disciplines, including stem cell biology, genome engineering, and transplantation. In the past, similar attempts to treat genetic disorders have come up short because researchers had not combined these complex fields. Tolar said being able to collaborate with others in this way using the open research environment and resources of the U of M is inspiring.
“The team that has been assembled to do this is the best you could have gotten,” he said. “It has been incredible to see how other researchers around the table light up and say, ‘I had no idea that you existed.’”
While it’s difficult to forecast when a clinical trial might take place, Osborn and Tolar hope the end goal of their work leads to a successful treatment of more than just the two diseases, Fanconi anemia and epidermolysis bullosa. Often, studying specific diseases can help find wider-reaching treatments for other diseases. Scientists have found that one of the most common forms of cancer, breast cancer, is in part caused by a gene in the Fanconi anemia pathway of the genome.
“We don’t focus on individual diseases so much as on how to improve the practice of medicine,” Tolar said. “We are motivated by the possibility that this ushers in a decade where regenerative medicine can truly make a difference in people’s lives.”
Life Sciences Innovation Showcase
Learn more about Tolar and Osborn’s work and that of other leading medical innovators at the Life Sciences Innovation Showcase, May 20, at the IDS building in downtown Minneapolis:
Agenda:
- 1-1:30 p.m. – Registration
- 1:30-3 p.m. – Innovation presentations
- 3-5 p.m.- Innovation exhibits with drinks and hors d’oeuvres
Speakers from the U of M:
- Jakub Tolar, MD, PhD, Department of Pediatrics: Fanconi Anemia Gene Editing by CRISPR/Cas9 System
- James Krocak, MS, MBA, Medical Devices Center: Lung Pacing for Ventilator-Induced Diaphragm Damage
- Jaime Modiano, VMD, PhD, Department of Veterinary Clinical Sciences: A Method for Prognostic Classification of Canine Lymphoma
Speakers from Mayo Clinic:
- Paul A. Friedman, MD: Non-invasive Assessment of Serum Potassium Levels through Wireless Monitoring of ECG
- Brandon J. Tefft, PhD: Magnetics, Nanotechnology and Rapid Endothelialization of Implanted Cardiovascular Devices
- Jeanne M. Huddleston, MD: Surgical Optimization System
The event is hosted by the U of M’s Office for Technology Commercialization and is sponsored by Schwegman, Lundberg, Woessner and Gray Plant Mooty.
