A step closer to a new treatment for Huntington's Disease

Researchers at the University of California, Davis have just published a really interesting paper in Molecular and Cellular Neuroscience. Huntington’s Disease is a neurodegenerative disease that arises when an expansion of trinucleotide repeat (CAG) in the gene that encodes the huntington protein (called HTT) occurs. The CAG repeat is found naturally in the HTT gene, however in patients with Huntington’s Disease, this repeat can be found in stretches containing greater than 30 (and up to hundreds) repeats.

Currently, there is no cure for Huntington’s. Ideally, being able to decrease or eliminate the expression of the mutant HTT gene in the specific neurons of Huntington’s patients would work to reverse or cure the disease. Unfortunately, this type of therapy isn’t possible yet. In 2006, a new technique to switch off gene expression (and protein production) was developed by Drs. Mello and Fire (they shared the Nobel Prize for this!) called RNA interference, or RNAi. In a nutshell, this technique blocks the translation of RNA molecules into protein and results in decreased protein amounts overall. There are several limitations to using this RNAi technique in humans as a disease therapy. Among these are -- preventing the degradation of RNAi probes, developing ways to target the RNAi to the specific cell, and getting the probe into the appropriate cell. In this latest paper, Dr. Nolta and colleagues have taken a step closer to solving one of these obstacles; getting the RNAi probes into the neurons and decreasing HTT expression. They placed the RNAi probes into mesenchymal stem cells and used these cells as carriers to transport the probes to the neurons with the HTT expansion. Mesenchymal stem cells (MSGs) are excellent carriers because they can be harvested from bone marrow or fat tissue of patients (therefore MSGs are safe and have anti-inflammatory effects) and can be expanded in cell culture. Additionally, MSGs have been shown to transfer fairly large organelles and molecules from one cell to another. In this paper, MSGs were infected with the RNAi probe and used to deliver that probe to the HTT expressing neuron in the same culture. Once the probe was successfully transferred to the neuron, levels of HTT gene expression declined, eliminating one of the factors that leads to the development of Huntington’s. There is still more work to be done before this is an actual therapy for those with Huntington’s, however this paper helps move the idea one step closer to reality.

http://www.ncbi.nlm.nih.gov/pubmed/22198539

questions or comments? Feel free to email me directly -- jck@n3scicom.com


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