Tiny bubbles of gene therapy, which can may help treat hemophilia (lat. Haemophilia, also spelt as hemophilia) were developed by researchers at the Center for Cardiovascular Research at the University of Hawaii. Burns School of Medicine. Scientists hope that patients with hemophilia could one day be treated with gene therapy delivered by tiny bubbles. The microbubbles are made of lipid molecules that won’t dissolve in water. The bubbles are made with DNA that expresses therapeutic genes, and are then injected into the bloodstream. As the bubbles pass through the liver, a beam of ultrasound pops them, and the DNA is deposited in the liver cells, where it makes the missing clotting factor. Hemophilia is an attractive target for gene replacement therapy because the disease results from a single gene mutation, and low levels of the normal protein can restore clotting function.

The study was led by Dr. Cindy Anderson and Dr. Chad Walton, who were both studying at UH’s John A. Burns School of Medicine (JABSOM) during the breakthrough phase of research. Dr. Cindy Anderson at that time was a graduate student in the Cell & Molecular Biology Department at JABSOM and is now an Assistant Professor at Georgetown University. Dr. Chad Walton was an Assistant Professor of Medicine at JABSOM and is now an assistant to the Vice-Chancellor for Research at UH Mānoa.

The team of scientists took genetic material that can elicit the production of factor IX (FIX) and placed it within miniscule microbubbles composed of lipid molecules that do not dissolve in water. The therapy was then injected into the bloodstream of mice with hemophilia B. As the microbubbles passed through the bloodstream they were hit by a beam of ultrasound that dispersed the genetic “payload” and deposited it into liver cells targeted for their ability to stimulate the production of FIX. The technique is known as ultrasound-targeted microbubble destruction (UTMD).

The animals subsequently showed both reductions in clotting time and increased FIX levels. An additional set of mice were treated via UTMD and evaluated for long-term effects, the results of which demonstrated a persistent reduction in average clotting time 160 days after one administration of the therapy.

According to Ralph Shohet, Professor and Center Director, hemophilia is a chronic debilitating disease. If they can treat it simply, cheaply and noninvasively with gene therapy they will have helped to fulfill the promise of the modern medical era. The technique could provide an alternative to current treatments for hemophilia, which require frequent injections of a protein (Factor VIII or Factor IX), which is expensive and inconvenient. Hemophilia affects about 20,000 men and boys in the United States and perhaps 400,000 worldwide. Most affected individuals have a severe form of the disease and suffer from frequent and spontaneous bleeding episodes that can result in serious complications. Their study was funded by the American Heart Association and the U.S. National Institutes of Health.