Research team explores 'paradigm shift' for treating orphan diseases

Patients suffering from spinal muscular atrophy (caused by a mutation in the SMN1 gene) can experience muscle weakness, loss of the ability to move, and even death. Focused on a small number of individuals with few other options, Zolgensma, the gene therapy that treats the disease, costs $2 million a dose — making it the most expensive drug on the planet.

SMA is just one of thousands of orphan diseases — individually rare, usually genetic diseases that collectively affect millions of people around the world. Specialized gene therapies are needed to treat each individual disease, which can be prohibitively expensive. Developing accessible, affordable treatments for orphan diseases requires a “complete paradigm shift”, says Dr. Mark Ungrin, PhD, associate professor in the Department of Comparative Biology and Experimental Medicine in the Faculty of Veterinary Medicine.

Ungrin and his colleagues have received $250,000 over two years from the New Frontiers in Research Fund (NFRF), federal funding that brings together diverse disciplines “in pursuit of breakthrough ideas and high-reward outcomes.” The “breakthrough” Ungrin and his interdisciplinary team are aiming for is developing a unified approach to make repairs, deliver replacement genes, precisely target cancer cells, and activate defences against infectious diseases. A common platform easily customized to the needs of the individual patient would make treating orphan diseases much more affordable, and therefore accessible.

“There is an urgent need for new, generalizable ways to repair or replace the function of damaged or mutated genes, and to treat cancer and infectious diseases” he says. The research team, which includes Dr. Constance Finney, PhD, associate professor in the Faculty of Science and Dr. James Wasmuth, PhD, associate professor in Ecosystem and Public Health at UCVM, will employ synthetic and molecular biology approaches in cultured cells and organoids.

“Synthetic biology circuitry can process information around what kind of cell it's in or what your current blood sugar level is, and then deliver a response that is customized to that environment and that context,” says Ungrin.

High-risk, high-reward research

The grant allows the team to explore new territory that brings together basic science, biomedical engineering, and health research. “It might not work,” says Ungrin. “There may be obstacles no-one has thought of. The challenge is that in science in general, research with predictable outcomes is by definition not something that has much potential to be revolutionary.”

The NFRF-E mechanism is designed specifically to address this sort of high-risk, high-reward research. This project, entitled Somatic Engineering - A New Approach to Medical Intervention, is among 117 research projects across Canada that NFRF has funded for their potential for “game-changing” results.

“The irreplaceable value of academic research is in the exploration of ideas that might not pan out, that don’t come with any guarantees and might never make a profit,” says Ungrin. “It means exploring concepts that could take us somewhere really interesting — but maybe you have to explore 10 of those concepts before you find the real game-changer.

"This type of funding opportunity is absolutely critical to being able to carry out those sorts of explorations, which lay the foundations for the medical advances and economic opportunities of the future.”