Friday, June 14, 2013

ISSCR: Gene therapy shows power of going back to the bench after being at the bedside

In gene therapy, modified viruses are used to insert corrected genes into patients' cells
Anyone who has followed the long twisted road of developing gene therapy knows the story of the big oops that happened with the first large trial in Severe Combined Immune Deficiency (SCID). This fatal disease is sometimes called “bubble boy” disease referring to a patient that was kept alive by living behind a clear barrier that protected him from the infectious agents that inevitably kill children with this genetic disease.

In that infamous trial, researchers harvested the patients’ own bone marrow stem cells, used a retrovirus to insert the gene needed to correct the defect, and gave the cells back to the patients. This cured the disease in 18 out of 20 kids. But five of them developed leukemia a few years later.

This sent the field scrambling. The result was the story told this morning in the opening talk of a plenary session of the International Society for Stem Cell Research annual meeting. They did two things. First they formed a seven-center international consortium hoping the large diverse group could collectively come up with solutions more quickly, and when the next trial began, recruit patients more quickly. They also went from the bedside back to the bench to figure out exactly what caused the leukemias.

One of the three leaders of the consortium, Indiana University’s David Williams, described the extensive effort to figure out how the virus that carried in the therapeutic gene caused the unwanted gene alteration that led to leukemia. They found that the virus caused a gene to be inserted next to a cancer causing gene that turned it on. They then set out to alter the virus to avoid this gene misplacement. That task was relatively rapid, however, compared to proving to the regulatory bodies that the change really did the trick. That required many different experiments spanning more than a year.

The resulting clinical trial is underway at five centers, and five of the first eight patients seem to be cured. None have shown any unwanted effects and the first child is two years out from his treatment. The consortium now has clinical trials underway for four diseases. Worldwide, gene therapy has shown promise in early tests in patients for at least 10 diseases.

CIRM has funded a team at Stanford to develop a way to make the bone marrow stem cell transplant aspect of these therapies even safer. You can read about that project here.

Williams talk highlighted the power of collaboration and bringing teams together within institutions and across institutional and state and national boundaries. CIRM has created more than 20 cross-border opportunities for collaboration. Those agreements can be found here. I also have to say I was proud to see someone from IU, my alma mater, featured as the opening speaker at a plenary session of such an important meeting. And the Hoosiers just made it into the international college baseball world series. A good week.


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