U of M Faculty-Led Team Awarded $1.8 Million to Develop Gene Therapy for Cockayne Syndrome

Christina Pacak, PhD, assistant professor in the Department of Neurology at the University of Minnesota Medical School, received a $1.8M grant to develop efficient manufacturing of a gene therapy for Cockayne Syndrome. 

Cockayne Syndrome is a rare accelerated aging disorder that has no disease- altering treatments available at this time. Symptoms can include, but are not limited to, accelerated aging, short stature, microcephaly, photosensitivity, neurological dysfunction, liver and digestive problems and damaged kidneys. 

“At the end of our three-year grant, we should be able to go to the Food and Drug Administration (FDA) for an investigational new drug (IND) meeting,” Dr. Pacak said. “We have three years to really optimize our gene therapy, show that it works, and at the end, we hope to have promising data that will support moving this therapy forward into a clinical trial.”

Dr. Pacak is a primary investigator of the study along with George Aslanidi, PhD, of the Hormel Institute - University of Minnesota, Medical Research Center. The three-year grant was awarded to the team in September by the Center for Biologics Evaluation and Research of the FDA.

Dr. Pacak’s interest in this work was inspired by a personal connection.

“Family friends of ours had a child with Cockayne Syndrome,” Dr. Pacak said. “So, it’s been something in the back of my mind, and once I had my own laboratory and was able to decide where I wanted to focus my research, I knew I wanted to explore developing a gene therapy for Cockayne Syndrome and to explore its disease mechanisms. With this grant, we can finally put more resources and focused effort towards this work.”

Throughout the process, the team will be collaborating closely with the FDA, holding quarterly and annual meetings about the project.

“A lot of times when you’re developing therapies, you do your best and try to touch on everything the FDA is going to ask you about at the IND meeting, but you don’t know exactly what they’ll want until you’re there,” Dr. Pacak said. “This way, they are facilitating — in a very streamlined manner — discussion and advice about the project during its process, not just at the end. It is a much more efficient process for developing translational therapies.”

The team’s goal is to optimize the production and validation of rationally-designed adeno-associated virus (AAV) vectors to develop gene replacement therapies. Cockayne Syndrome is a DNA repair disorder, and a gene replacement therapy would provide a healthy copy of the affected gene that is expected to have therapeutic effects. 

“In addition to developing these gene therapies for very rare disorders, we’re trying to understand the underlying mechanisms for diseases related to aging, such as dementia, and to identify therapeutic targets,” Dr. Pacak said. “With this therapy, our hope is that we can stop the disease in its tracks, drastically slow it down or delay its effects to achieve a better quality of life for these patients.”

Collaborators in the study include Peter B. Kang, MD, in the Department of Neurology at the U of M Medical School, and Kah-Wey Peng, PhD, of the Mayo Clinic.