November 6, 2009
LA JOLLA, CA—Using a gene therapy delivery system developed in the laboratory of Inder Verma at the Salk Institute for Biological Studies, an international team of researchers successfully treated two children with adrenoleukodystrophy or ALD, in which the fatty insulation of nerve cells degenerates. The genetic disorder leads to progressive brain damage and results in death within two to five years after diagnosis.
Although the children have not been cured, their condition has been stable for the last two years, and they are cancer-free, according to Patrick Aubourg, the French researcher who led the study published in the Nov. 6, 2009 issue of the journal Science. Verma was not involved in the gene therapy trial.
(ALD is the rare, inherited fatal disease in children that was the focus of the 1993 Oscar-nominated film “Lorenzo’s Oil” starring Nick Nolte and Susan Sarandon.)
Verma, Ph.D., a professor in the Laboratory of Genetics and holder of the Irwin Mark Jacobs Chair in Exemplary Life Science pioneered the use of stripped-down versions of HIV, the virus that causes AIDS, to ferry intact versions of genes that are defective or missing to cells throughout the body.
Prior to this innovation, viruses used as gene delivery vehicles could only infect actively dividing cells, which left out the vast majority of cells in the body, drastically limiting its utility. Verma’s modified HIV virus, however, a member of the lentivirus family, is capable of infecting non-dividing cells and delivering genes efficiently into a wide variety of cells.
The new gene therapy vector not only solved the efficiency problem but also appears to positively impact the safety concerns that had dashed gene therapy hopes years earlier when the only human gene therapy treatment that had been considered to be largely successful, turned out be riskier than realized. Out of 20 children treated for X-linked severe combined immune deficiency (X-SCID) – commonly known as the “bubble boy” syndrome – 18 were cured but three developed leukemia and one died of it.
About eight years ago Verma was first approached by Aubourg and the Salzman sisters, who had been pushing scientists and doctors to design a gene therapy study after they had learned that three of their children suffered from ALD, to consider making his lentiviral vector available.
Eventually, the virus was produced by CellGenesys, who had licensed the gene therapy vector technology from the Salk Institute, and Aubourg successfully treated two boys from Spain.
About the Salk Institute for Biological Studies:
The Salk Institute for Biological Studies is one of the world’s preeminent basic research institutions, where internationally renowned faculty probe fundamental life science questions in a unique, collaborative, and creative environment. Focused both on discovery and on mentoring future generations of researchers, Salk scientists make groundbreaking contributions to our understanding of cancer, aging, Alzheimer’s, diabetes, and cardiovascular disorders by studying neuroscience, genetics, cell and plant biology, and related disciplines.
Faculty achievements have been recognized with numerous honors, including Nobel Prizes and memberships in the National Academy of Sciences. Founded in 1960 by polio vaccine pioneer Jonas Salk, M.D., the Institute is an independent nonprofit organization and architectural landmark.