Disease Focus Series: Huntington’s Disease, a major new finding

This is the first post in a series focusing on stem cell advances related to specific diseases. Today we discuss Huntington’s Disease and a paper that came out yesterday in the journal Neuron that provides some significant insight into the mechanisms behind the disease. It is entitled:

Huntingtin Is Required for Mitotic Spindle Orientation and Mammalian Neurogenesis

Huntington’s Disease (HD) is a genetic disorder characterized by progressive neurological problems caused by neurodegeneration. The cause of HD was discovered to be mutations in a gene that was named “Huntingtin”. The exact mechanism by which these mutations cause HD remains somewhat unclear. The Huntingtin gene and protein are nonetheless a very attractive therapeutic target and we hope this line of research pays off in a treatment or cure for HD.

In the paper published yesterday by Dr. Sandrine Humbert of the Curie Institute in France, the authors described a key insight into how the Huntingtin mutations might cause HD, pointing to stem and progenitor cells of the nervous system.

They report that Huntingtin is required for normal neural progenitor cell division. Specifically, Huntingtin is essential for mitosis. When normal Huntingtin levels are reduced normal mitosis fails due to a disruption of the mitotic spindle machinery and cells frequently undergo apoptosis.  Cells are programmed to die when they detect serious problems with mitosis. This is one likely mechanism by which the mutations in HD lead to cell death in the brain.

Altered Huntingtin function would also disrupt neurogenesis which drives normal growth of the nervous system. So a second interesting aspect of this paper is that it suggests that HD may have developmental origins even though it typically manifests later in life.

What this means is that events that occur early in life due to the mutations in Huntingtin make lead to HD decades later. This is hugely important because it suggests there may be a long therapeutic window of time during which HD can be prevented before symptoms even manifest! It also makes detection earlier in life all that much more important.

A similar, but unique kind of delay appears to be true of Alzheimer’s Disease as well.

I will discuss Alzheimer’s Disease in the next post in the disease series.