When the first cases of nvCJD began to appear in the United Kingdom, scientists couldn't understand how eating beef from BSE infected cows could cause such a similar degenerative brain disease in people.

The lack of knowledge about how prions make their way from the gut, where the beef is digested, into our brain, where it wreaks havoc, has made it very difficult to treat people with the disease or to prevent it.

Now, in the July 19 issue of Neuron, Adriano Aguzzi and colleagues identify the primary route by which prions invade the nervous system.

Aguzzi and colleagues at the University Hospital of Zürich had previously shown that after entering the body through the gut, prions take up residence in the spleen and lymphoid organs, where they multiply without causing any obvious symptoms.

Sympathetic nerves connect the central region of the spinal chord to the spleen and lymphoid organs. Therefore, in their current work, the team removed sympathetic nerves from mice in different ways. They then injected prions into the gut of mice.

They found that the progression of the disease was dramatically slowed. They then infected mice that had extra sympathetic nerve connections to the lymphoid organs and found that disease progression was more rapid than usual.

Because the rate at which prions march towards the brain is limited by the sympathetic nervous system, this system is an obvious target for researchers interested in preventing the progression of variant CJD. For example, there may be ways to slow or stop the transport of prions within the sympathetic nerve fibers.

"The sympathetic nervous system is a bottleneck and a window of opportunity arises when a person has infected himself with prions but before symptoms develop in the brain," says Aguzzi.

[Contact: Adriano Aguzzi]

20-Jul-2001