Scientists working on innovative treatments for people with hereditary diseases report they were able to repair genetic mutations responsible for cystic fibrosis in stem cells.
The research led by scientists at The University of Texas Health Science Center at Houston (UTHealth) appeared in Stem Cell Reports, the official journal of The International Society for Stem Cell Research.
Tens of thousands of people worldwide have this life-threatening disease that clogs their lungs with mucus and makes it increasingly hard to breathe. The disease causes chronic bacterial infections in the lung and gradual lung destruction.
The mutations were corrected in stem cells derived from people with cystic fibrosis using zinc finger nuclease-mediated genome editing.
Brian R. Davis, Ph.D., the study’s senior author and director of the Center for Stem Cell and Regenerative Medicine at UTHealth, described the research as promising but early.
“We’ve created stem cells corrected for the cystic fibrosis mutation that potentially could be utilized therapeutically for patients,” he said. “While much work remains, it is possible that these cells could one day be used as a form of cell therapy.”
Even further in the future, Davis said, the cells might be used to generate new organs such as a lung. “This has been done to the hearts and lungs of mice. You basically take the organ, remove the existing cells and reseed the organ scaffolding with new stem cells,” Davis said.
More immediately, Davis believes both the mutant and corrected stem cells could provide scientists with new research tools to evaluate encouraging cystic fibrosis treatments.
People with cystic fibrosis have mutations in a gene called CFTR, producing a defective protein. This interferes with the regular flow of salt and fluids in and out of cells of the lungs. When the flow is impeded, a cascade of problems occurs.
Davis and his colleagues ran tests to demonstrate that the corrected CFTR protein worked normally.
“This study points to a strategy for developing treatments for cystic fibrosis, including patients with rare forms of the disease,” said Eric J. Sorscher, M.D., study co-author and professor of hematology and oncology at the University of Alabama, Birmingham, School of Medicine.
The scientists began the research by taking skin cells from people with cystic fibrosis and converting them into a type of stem cell called an induced pluripotent stem cell. They then corrected the genetic mutation and produced a new line of CFTR mutation-free stem cells.
The genetic correction was accomplished precisely, in many ways similar to the cut and paste correction used in word processors.
Right now, the median age of survival of people with cystic fibrosis is 41 years of age, but many children still die from the disease.
“Cystic fibrosis is one the most common inherited genetic diseases,” said Davis, whose laboratory is in the Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases.
If both parents are carriers for the defective gene, their children have a one in four chance of getting cystic fibrosis.