Understanding the pathways that lead to nerve cell death in Huntington’s disease and other neurodegenerative disorders.

Dr. Ellerby is an expert on cell death in neurodegenerative disorders such as Huntington's disease, a progressive inherited disorder that attacks both motor coordination and thinking ability. Dr. Ellerby and her Buck colleague Dr. Robert Hughes recently discovered a new lead to potential drug therapies for Huntington's disease by focusing on a mysterious protein linked to the illness, the huntingtin protein (Htt).  Huntington's disease stems from a gene mutation that produces an abnormal form of the huntingtin protein, which breaks down into toxic fragments.  These fragments accumulate in neurons, which malfunction and eventually die.  Dr. Ellerby and her team identified a set of enzymes that help split up Htt into fragments, and whose activity contributed to nerve toxicity. In a novel discovery, the lab found this harmful activity in a class of enzymes already implicated in stroke, cancer, and other disorders.   Drug researchers have already developed experimental compounds to inhibit these enzymes, called the matrix metalloproteinases (MMPs).  Dr. Ellerby’s work suggests that inhibiting the MMPs may lessen symptoms of Huntington's disease and prevent nerve cell death.  In a 2010 article about this research, Dr. Ellerby was one of the lead authors of the cover story in the prestigious scientific journal Neuron.

The Ellerby lab is also exploring possible methods to stimulate the growth of new nerve cells to replace those lost in Huntington’s disease sufferers.

http://www.buckinstitute.org/ellerbyLab