HD research news - medical research into treatment & prevention

Clumps: villain or victim?

The mystery deepens. Dr. Michael Greenberg and Dr. Frederic Saudou Childrens Hospital, Boston, focused on studying in a rats brain the same kind of cells that are affected in human brains with Huntington's disease. Their results are reported in the October 2 issue of the journal Cell.

They took a piece of the Huntington's disease-causing gene and put it in cultured striatal neurons. The cells died in a way characteristic of a particular kind of death, called "apoptosis" or "programmed cell death" . Greenberg and his group wanted to know if the protein had to be in the nucleus to kill. They put an address on the gene producing mutant hungtin (the expanded version of the protein); the address said, "Get out of the nucleus and stay out."

Amazingly, the cells lived!

They also tried to separate the effects of the aggregates themselves - from cell death. Greenberg and his group suggest that the fragment itself containing the polyglutamines may be toxic, even if it is not aggregated. They even question whether the aggregates might be the cells way of protecting itself by swooping up the fragments, clustering them together and trying to digest and destroy them.

Recently, other investigators have found that the aggregates seem to be ushered (by proteins called "chaperones") over to the cells digestion machinery (called proteosomes), but perhaps the aggregates are too big and get stuck in its craw.

Dr Harry Orr and his group at the Institute of Human Genetics, University of Minnesota, had similar findings. They created a new transgenic mouse containing a gene that causes spinocerebellar ataxia 1 which, like Huntington's disease, contains too many CAG repeats. When Dr. Orr kept the protein out of the nucleus of cells, the life of the animal was saved. The next step is to translate these revelations to human practice.