X-Message-Number: 13295 Date: Thu, 24 Feb 2000 22:21:49 -0500 From: Jan Coetzee <> Subject: Vaccine to protect brain Report: Vaccine Protects Against Stroke, Epilepsy WASHINGTON (Reuters) - Researchers said on Thursday a new approach combining gene therapy and vaccination has prevented epileptic seizures and brain damage in rats and suggested it could eventually be tried in humans. A team at the Jefferson Medical College in Philadelphia said their vaccine, which is given orally, marshaled the immune system to protect brain cells that are usually killed during and after a stroke or a seizure. ``It protects them significantly from ... insults such as an epileptic seizure or a stroke for at least five months after a single oral dose,'' Dr. Matthew During, a professor of neurosurgery who led the study, said in a statement. The researchers, who reported their findings in the journal Science, said it might be used to help protect people considered at high risk of a stroke or a seizure, such as those who have undergone heart bypass surgery. And they say the approach might work against a whole range of diseases involving the central nervous system, from Parkinson's to Lou Gehrig's disease (motor neuron disease). ``I think it represents a new platform of technology, a sort of revolutionary approach to the treating of brain diseases,'' During said in a telephone interview. ``What we have shown here is you can harness the amazing specificity of the immune system so it can go in and act as a scalpel, so to speak, to target specific brain functions.'' During and colleagues, working in collaboration with the team at the University of Auckland in New Zealand, targeted a brain protein, part of the NMDA receptor. This bit of the receptor -- which is a chemical doorway into a brain cell -- is called NR1. NMDA receptors are important not only for brain development and learning, but are involved in a range of diseases including epilepsy, dementia and the injuries caused by stroke. The researchers made up a vaccine that caused the rats to first produce the protein for this receptor, then recognize it as abnormal and block it. Best of all, the effect was temporary and seemed to work only in direct response to a brain injury. They used an adeno-associated virus -- a small kind of virus that does not make people sick but which is very good at infecting cells -- to carry DNA from the NMDA receptor into the bodies of their experimental rats. They fed this vaccine to the rats, who developed antibodies specifically targeting this bit of the receptor, and when the scientists induced an epileptic seizure in the rats a month later, only 2 of 9 vaccinated rats showed signs of a seizure. ``About 70 percent of the rats should have gone into seizures, whereas only 20 percent of the rats immunized against the NMDA receptor did so,'' During said. They killed the rats and looked at their brains and found no sign of the damage usually caused by the chemical used to induce a seizure. During thinks the effect might be permanent, but they have to test the rats further to see if they are protected against repeated injuries or seizures. The brain is exceptionally fragile because, for reasons not yet fully understood, when one brain cell dies, as in a blow to the head or a stroke, it sends out signals that kill other, uninjured cells surrounding it. During's team said their study indicates their vaccine could prevent this kind of damage as well. To test this, they vaccinated rats and induced a stroke. The rats did have strokes, but the area damaged was much smaller in the vaccinated rats, they said. Normally, a vaccine should not be able to get into the brain because of a system called the blood-brain barrier that protects from damage caused by the immune system. But the researchers noted that sometimes cancer can break down this barrier, allowing immune system compounds to cause inflammation of the brain. They think they may have breached the blood-brain barrier in the same way, but only temporarily, when they intentionally damaged the rats' brains. The rats were closely watched to ensure the vaccine did not damage their brain cells in another way. ``They were completely normal in terms of motor behavior,'' During said. ``If anything, the rats were a bit smarter,'' he added. But he declined to go any further, saying that part of the study had not yet been published. Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=13295