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University of North Carolina researchers publish study on gene therapy of Alpha-1
CHAPEL HILL, NC – In a kind of molecular gymnastics, scientists at the University of North Carolina at Chapel Hill School of Medicine have devised a gene therapy cocktail that has the potential to treat some inherited diseases associated with “misfolded” proteins — including Alpha-1 Antitrypsin Deficiency (Alpha-1).
Like strings of beads attached end-to-end on a chain, a given sequence of a protein’s amino acids usually folds into a characteristic, three-dimensional structure. When “misfolded,” a mutant protein’s natural biological role may be compromised, sometimes with implications for disease development.
This is one of the challenging research arenas chosen by R. Jude Samulski, PhD, director of the UNC Gene Therapy Center and a professor of pharmacology. “Among the roughly 5,000 genetic disorders for which the majority of genes have been mapped, there’s a subset in which the mutant or misfolded protein by itself can cause disease symptoms – this is in addition to the lack of a normal gene,” he says. “And that has added another layer of complication faced by the clinical research community when trying to develop and test new treatment approaches to disorders that result from toxicity associated with cellular accumulation of misfolded proteins.”
Among these disorders are Alpha-1, cystic fibrosis, Huntington’s disease, amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s disease), and Alzheimer’s disease.
The report published in the on-line Early Edition of the Proceedings of the National Academy of Sciences is focused on a gene therapy approach to Alpha-1, which can lead to serious lung and liver disease in children and adults.
In the study, first- and co-corresponding author with Samulski, Chengwen Li, PhD, research assistant professor of pediatrics, conducted a series of gene therapy experiments using a mouse model of alpha-1 disorder. All involved the adeno-associated virus (AAV) vector as a molecular delivery truck.
Researchers at the University of Massachusetts and University of Florida have published gene therapy studies on humans done with the same AAV virus vector.
