Viruses may be a useful therapeutic arsenal against the most pervasive forms of brain tumors — provided they can be engineered to be safe, a recent study by researchers at the medial school reported this week.
When vesicular stomatitis virus — a lab-created virus distantly related to the rabies viruses — is administered into the bloodstream, it can find its way into the brain and kill deadly brain tumors, the study found.
The finding may have implications for a novel therapeutic technique for treating brain tumors down the line, if the group can perfect the technology and see it through clinical trials, neurosurgery professor Anthony von den Pol said.
Brain tumors, which affect over 200,000 Americans annually, are currently incurable and generally lead to mortality within months. This frightening statistic, coupled with the currently imperfect forms of treatment for the condition, make the discovery potentially groundbreaking, medical school Dean Robert Alpern said.
“The basic idea is that brain tumors in adults are impossible to treat,” he said. “It’s almost guaranteed that if someone is diagnosed with the condition, that they will die. We really need a treatment that is toxic that can selectively enter tumor cells but not normal cells, to cure this.”
In the study, the group transplanted human brain tumors into mice brains and injected the VSV virus into the tail end of the mouse. Three days later, the tumor cells, which had been infected with the virus, were dying or dead, while the normal brain cells had been spared, von den Pol said. Before the technology can go to human trials, he said, the researchers must conduct further tests to be completely certain it will not harm non-cancerous cells.
Existing treatment methods for brain tumors include chemotherapy, radiation and surgery, which work by slowing down the progress of a tumor but are typically unable to eliminate all tumor cells. As a result, regrowth of tumors begins within days, von den Pol said.
“There isn’t any treatment right now that is 100 percent successful,” he said. “There is a possibility that a virus can go into the brain and infect one tumor cell and then create thousands of virus particles that then go on to infect other tumor cells. So the virus can potentially act as a self-amplifying anti-cancer agent.”
The shortcomings of current therapy options reflect the invasiveness of brain tumors, which divide rapidly and migrate around the host brain. This mobility makes it difficult for existing procedures to find and remove all cancerous cells, von den Pol said. Chemical methods, he said, such as drug administration, have traditionally proven to be inadequate, since the brain contains a blood-brain barrier that restricts the entry of numerous substances.
The viral approach to cancer treatment is not new, although it is the first time a viral candidate of this level of promise has been isolated, Guido Wollmann, a co-author on the study, said. Scientists have been testing the technique for several decades, but earlier experiments used viruses that only infected particular tumor cells, Wollman said.
Wollmann said that this technique fails because brain tumors are composed of many different types of tumor cells, and these individual cells mutate at a rapid rate over the course of the disease, leading to increased heretogeneity over time.
“If you are very specific in your target, you actually limit yourself a lot,” he said. “That’s where we came in, to find a virus that has a much broader spectrum of infection — which, in theory, in capability to get into every cell.”
But in reality, the VSV never enters normal body cells, Wollman said. Viruses can be fought off by normal cells, which have defense mechanisms — which tumor cells lack — that curb the process of infection. This gives the virus the ability to distinguish between normal and cancerous cells, and selectively kill tumor growth, he explained.
The lab is currently engaged in finding ways to make the technology safer in humans. Von den Pol said the challenge is now to eliminate the probability of the virus’ infecting non-tumor cells — a process that can be engineered by genetic mutations, additions and deletions — while still retaining its ability to infect viral cells.
http://www.yaledailynews.com/articles/view/23721
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