"I killed smart people to eat their brains and all I got was this lousy prion disease." This was a T-shirt slogan I came up with and posted as a comment in ![[info]](http://stat.livejournal.com/img/userinfo.gif)
sunshine__girl's journal. (I couldn't find the original post.)
I've been thinking about prion diseases tonight. A family friend of a friend is having the plug pulled on her tomorrow after suffering rapidly degenerative neurological symptoms over the past two weeks that have been diagnosed as Creutzfeldt-Jakob disease. CJD is one of those ultra-rare diseases you hear bandied about week after week on House that the patient never has. The reality of prion diseases isn't as funny as that joke I made about prions years ago.
I'm not a molecular bioengineer or anything, but it seems like it would be possible to manufacture a virus that would inject a heat-shock-promoted chaperone sequence designed to bind and capture prions to transform them back to their native conformational state. Once the patient is infected, you can either rely on the immune system to respond to infection by causing a fever or you can put the patient in a hot tub. This may kill the virus and would activate the by-then injected DNA sequence. The prion-hunting chaperones would be assembled and clear the infected cell of prions.
There's one issue I don't have a solution for. Since prions reside in nerve cells, that's where we'd want to target the viral vector. While the immune system is normally cause for concern to viral gene therapy techniques, the brain is immunologically privileged, and for good reason. The usual immunological defensive tricks involve invoking cell-death routines and sending in the cleaners to pick up the pieces. Dismantling brain cells is bad news. (That's what the prion disease is doing, after all.) The problem, however, relates to how to safely get rid of the virus if the immune system doesn't see it. It'd be designed for low virulence of course, but who wants to be saved from a devastating neurological disease only to live in fear of a potentially mutable virus hanging around in their brain that could reek havoc later on?
Potential pitfalls aside, several pieces of this problem are hard. Unless such a chaperone already exists and is discovered, both unknown to me and unlikely, the protein would have to be bioengineered. Maybe in 10-20 years time we'll have the understanding and technology to create proteins as complex as prion-selective chaperones.
I'm enjoying thinking about this stuff. It's preparing me for the conference on the genetics of neurological diseases I'm going to in Paris during spring break next year.
Fri, December 7, 2007 - 2:44 AM
permalink
sunshine__girl's journal. (I couldn't find the original post.)I've been thinking about prion diseases tonight. A family friend of a friend is having the plug pulled on her tomorrow after suffering rapidly degenerative neurological symptoms over the past two weeks that have been diagnosed as Creutzfeldt-Jakob disease. CJD is one of those ultra-rare diseases you hear bandied about week after week on House that the patient never has. The reality of prion diseases isn't as funny as that joke I made about prions years ago.
I'm not a molecular bioengineer or anything, but it seems like it would be possible to manufacture a virus that would inject a heat-shock-promoted chaperone sequence designed to bind and capture prions to transform them back to their native conformational state. Once the patient is infected, you can either rely on the immune system to respond to infection by causing a fever or you can put the patient in a hot tub. This may kill the virus and would activate the by-then injected DNA sequence. The prion-hunting chaperones would be assembled and clear the infected cell of prions.
There's one issue I don't have a solution for. Since prions reside in nerve cells, that's where we'd want to target the viral vector. While the immune system is normally cause for concern to viral gene therapy techniques, the brain is immunologically privileged, and for good reason. The usual immunological defensive tricks involve invoking cell-death routines and sending in the cleaners to pick up the pieces. Dismantling brain cells is bad news. (That's what the prion disease is doing, after all.) The problem, however, relates to how to safely get rid of the virus if the immune system doesn't see it. It'd be designed for low virulence of course, but who wants to be saved from a devastating neurological disease only to live in fear of a potentially mutable virus hanging around in their brain that could reek havoc later on?
Potential pitfalls aside, several pieces of this problem are hard. Unless such a chaperone already exists and is discovered, both unknown to me and unlikely, the protein would have to be bioengineered. Maybe in 10-20 years time we'll have the understanding and technology to create proteins as complex as prion-selective chaperones.
I'm enjoying thinking about this stuff. It's preparing me for the conference on the genetics of neurological diseases I'm going to in Paris during spring break next year.
