Gene therapy that is capable of stalling the progression of Huntington's disease, scientists from California Institute of Technology (Caltech) have suggested.
Huntington's disease is a neurodegenerative disorder with a genetic basis. The disorder has its roots in a mutation in a protein called huntingtin, or Htt. (The gene itself is also referred to as the huntingtin gene.)
Advertisement"Gene therapy in these models successfully attenuated the symptoms of Huntington's disease and increased life span," said Paul Patterson, the Anne P. and Benjamin F. Biaggini Professor of Biological Sciences.
The researchers began to look at the efficacy of two different intrabodies that had been shown, in cell cultures and fruit-fly models, to reduce the accumulation of toxic Htt protein.
To see whether those effects would hold true in mammalian systems as well, the team tested the intrabodies in a series of five different mouse models of Huntington's.
They found that one of the two intrabodies had some negative results, actually increasing Huntington's-related mortality in one model.
But the other intrabody- called Happ1- was an unqualified success, restoring motor and cognitive function to the mice, and reducing neuron loss as well as toxic protein accumulation. And in one model, it increased both body weight and life span.
"Our studies show that the use of intrabodies can block the parts of mutant huntingtin that cause its toxicity without affecting the wildtype, or normal, huntingtin-or any other proteins," said Patterson.
In other words, he says, this has the potential to be the kind of "silver-bullet therapy" that many medical researchers look for.
Despite the fact that this disorder has a single-gene origin, current treatments tend to address the symptoms of the disease, not its cause. That means it is currently impossible to prevent the disease from doing significant damage in the first place.
The study appears in the Journal of Neuroscience.