Just as Botox earned a new reputation, going from solely causing botulism to being an innovative cosmetic procedure that erases lines and wrinkles, salmonella bacteria might be in store for medical reinvention. Research now shows the strain of bacteria most associated with food poisoning could aid in the fight against a very advanced form of brain cancer — glioblastoma.
The study, published in the journal Molecular Therapy Oncolytics, found that with a few genetic tweaks scientists were able to turn the bacterium Salmonella typhimurium into a cancer-targeting bullseye that causes tumors to self destruct. Animal trials that received this treatment showed promising results. It worked in 20 percent of rats stricken with extreme cases of glioblastoma by extending their lives over 100 days, which translates to 10 human years. The tumors eventually went into complete remission.
“Since glioblastoma is so aggressive and difficult to treat, any change in the median survival rate is a big deal,” said Jonathan Lyon, a Ph.D. student working with Ravi Bellamkonda, Vinik Dean of Duke’s Pratt School of Engineering. “And since few survive a glioblastoma diagnosis indefinitely, a 20 percent effective cure rate is phenomenal and very encouraging.”
Glioblastoma, is the most aggressive form of brain cancer. It’s aided by the blood-brain barrier, which is a protective sheath that separates brain tissue from its blood vessels. And that biology is what makes it so difficult to effectively attack the disease with drugs.
Surgery has also not proved to be a successful option for removal of the cancer because tiny remnants of the cancer left in the head region can spawn new tumors. The median survival rate, even with the best treatment, is 15 months. Only ten percent of patients diagnosed with glioblastoma live five years.
How the Salmonella Bacteria Was Manipulated
Previous studies have shown that the presence of bacteria can cause the immune system to accidentally recognize and begin attacking tumors. But by themselves, genetically detoxified strains of S. typhimurium have proved to be ineffective in fighting cancerous cells.
However, in choosing a detoxified strain of S. typhimurium that was deficient in an enzyme called purine, it changed the behavior of the bacteria. Because of the lack of purine, S. typhimurium sought the supply of the enzyme in other parts of the body. Tumors are naturally an excellent source of purine, and that’s what causes throngs of the S. typhimurium bacteria to be magnetically attracted to it.
“A major challenge in treating gliomas is that the tumor is dispersed with no clear edge, making them difficult to completely surgically remove. So designing bacteria to actively move and seek out these distributed tumors, and express their anti-tumor proteins only in hypoxic, purine rich tumor regions is exciting,” said Bellamkonda, corresponding author of the paper. “And because their natural toxicity has been deactivated, they don’t cause an immunological response. At the doses we used in the experiments, they were naturally cleared once they’d killed the tumors, effectively destroying their own food source.”
Researchers also closely examined the 80 percent of rodents that did not survive. The treatment didn’t change the survival rates of the rats, so scientists believe that there might have been inconsistencies in the how the bacteria penetrated the brain, or that the growth of the aggressive tumor moved faster than S. typhimurium within the body. Next, researchers are looking into programming more of the bacteria to create new drugs that could have stronger reactions in tumors.
“This was our first attempt at designing such a therapy,” said Lyon. “There is some nuance to the specific model we used, thus more experiments are needed to know for sure.”