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news.Researchers have discovered that drugs commonly used to treat psychiatric illnesses and blood disorders, including Sanofi-Aventis' anticoagulant Lovenox and GlaxoSmithKline's antipsychotic Stelazine, may protect the brain cells that die in patients with Huntington's disease, possibly delaying the onset and slowing the progression of the disease.
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These findings may offer new treatment options for Huntington’s disease, which currently has no cure.
Huntington’s disease is a neurological disorder caused by a mutation in the gene that makes the protein huntingtin. The mutation creates a long chain of the amino acid glutamine at one end of the protein. The length of the chain directly correlates with age of onset of the disease, with longer chains leading to symptoms earlier in life.
In previous studies, Dr Ilya Bezprozvanny, associate professor of physiology at UT Southwestern, established that one of the defects that leads to death of nerve cells with the mutant huntingtin protein is improper regulation of calcium due to errant signals in the cells. Calcium is inappropriately released from its storage area in the cells, and eventually the cells die.
In the current study, using the medium spiny neurons of mice that carry a copy of the mutated human huntingtin gene, Dr Bezprozvanny and colleagues found that treatment of the cells in culture with the drug enoxaparin (marketed by Sanofi-Aventis as Lovenox) prevented inappropriate calcium release, and prevented cell death.
Because the signals that lead cells to die can come from multiple pathways, Dr Bezprozvanny then determined which cell death pathway affected the nerve cells carrying mutant huntingtin. He found that the nerve cells’ mitochondria, the parts of the cell that create energy, released a protein called cytochrome c through a pore just before dying.
From other studies, it was known the antidepressants nortriptyline and desipramine, and the antipsychotic trifluoperazine (marketed as Stelazine by GlaxoSmithKline) block the mitochondrial pore through which cytochrome c and other death signals are released. By treating the mouse nerve cells containing the mutant huntingtin protein with these drugs, Dr Bezprozvanny was able to block the nerve cells from dying.
The next step, according to Dr Bezprozvanny, will be to work with other researchers to test these drugs in whole animal models of Huntington’s disease, and see if cell death and loss of motor function observed in these models can be prevented.