Pedro Lowenstein, M.D., Ph.D., and Maria Castro, Ph.D., are beginning clinical trials of gene therapy for glioblastomas.

Hope on the Horizon

Breakthrough research in gene therapy shows promise for treating brain tumors

issue 2 | Fall 2012

Although the incidence of brain tumors in children is relatively low (approximately 3,000 annually in the U.S.), brain tumors account for nearly 20 percent of all cancer in children up to 15 years of age, and are the leading cause of cancer deaths in pediatric oncology. Five-year survival rates from brain tumors are approximately 66 percent for children ages 0—19 years, but vary according to tumor type. Glioblastomas are particularly lethal.

The good news is that new techniques in gene therapy to treat glioblastomas have shown remarkable survival rates of approximately 70 percent in animal trials. Human trials with adults, led by preeminent researchers Maria Castro, Ph.D., and Pedro Lowenstein, M.D., Ph.D., will begin shortly at the University of Michigan, and the trials may soon include pediatric patients.


The difficulty in cancer treatments for children — particularly in brain tumors — is that radiation and chemotherapy target developing cells with fast duplication rates. "However, children's brains are composed of nothing but cells that multiply and grow quickly," explains Karin Muraszko, M.D., pediatric neurosurgeon and chair of the Department of Neurosurgery at the University of Michigan. "Standard therapies can have devastating side effects on a developing brain, in addition to being generally ineffective in treating glioblastomas."

"Developing new therapies for brain tumors has been a major goal throughout my career in pediatric neurosurgery, and Dr. Castro's and Dr. Lowenstein's research has had a similar focus," continues Muraszko. "Our hope is that their new therapies will be successful in killing the tumor without killing brain cells, especially in children."


"We have developed a new gene therapy for brain tumors, specifically glioblastomas," explains Castro. "The therapy consists of two genes. One kills the cancer cells, and the other one trains the immune system to recognize and destroy malignant cells that remain or even recur."

These two therapeutic genes are encoded in adenoviruses that act as vectors to deliver the genes. "Our first adult patients will be treated with this therapy very soon," continues Lowenstein. "When we establish that it is safe in adults, we hope to quickly expand the trial to pediatric patients. Because this therapy uses the immune system to eliminate the tumor, it will be interesting to see whether our predictions will hold with pediatric patients, given the differences between the immune systems of adults and children."


"The advantage of the gene therapy is that patients will need less chemotherapy and radiation, but it's critical in children," explains Castro. "Those aggressive treatments leave kids with very bad sequelae, such as behavior and memory problems. These gene therapies would circumvent the side effects of conventional therapy."

"This is a new, exciting phase for the treatment of brain tumors both in adults and children because it's the first ever trial in human brain tumors that uses two different adenoviral vectors. It's really a first for mankind," says Lowenstein. "The University of Michigan is in a prime position to capitalize on this new technology because of the strength of their neurosurgical teams and the pediatric oncology group. It's the best place to spearhead this new technology."

Also In This Article:

Read more about Castro and Lowenstein, who are partners in research and in life.