HD research news - medical research into treatment & prevention

Cell Models: a potent new weapon in the HD research lab

Abigail S. Hackman, Ph.D., Center for Molecular Medicine and Therapeutics, University of B.C., Vancouver

"Since the devastating symptoms of HD are due to excessive death of nerve cells (neurons), the method of choice for many scientists is using cultured cells to model the disease processes leading to cell death.

To mimic the cell death that occurs in HD, Dr. Michael Hayden's lab developed a cell model to assess factors that promote or prevent cell death. In this model, fibroblast cells (a kind of cell often used in cell culture experiments) were damaged by low (sub-lethal) doses of chemicals that only kill cells when huntingtin is present. In other words, huntingtin made the cells more likely to die. This may mimic the later life onset of HD, in which accumulation of injuries or stress is needed to cause cell death.

In addition it has been shown in HD brains that huntingtin is cut up, or cleaved, into protein fragments. Similarly, huntingtin is also cut up in cell culture when the cells are dying. Fortunately, in the cell model, the effect of generating these fragments can be directly tested by instructing the cells to exclusively make the huntingtin fragments. Intriguingly, it was found that when cells made these huntingtin fragments, they were more likely to die than when they made the full-length huntingtin protein. Therefore, the cell model allows researchers to directly test the hypothesis generated from this data: that a drug to prevent the protein from being cut up could reduce cell death.

Another observation that was mimicked in cell culture is the formation of clumps, or balls, of aggregated huntingtin that were identified in affected regions of the brain of HD patients.

The cell culture model system is clearly valuable for understanding the basic mechanisms of cell death observed in HD. It allows scientists to isolate and model different steps of the disease pathway that occur over time. Furthermore, combining experiments from cells, along with results from animals and patients, allows the development of testable hypotheses for HD."

• This article is reprinted from HDSA's research newsletter, Toward a Cure.