According to investigators at the National Institute on Aging (NIA) Gerontology Research Center, two experimental drugs appear to prevent Parkinson''s disease-like brain damage and motor dysfunction in mice. The finding identifies a new approach for slowing or halting the progression of Parkinson''s disease that may one day help treat people who have it.
"Although one must be cautiously optimistic when moving drugs from animals to humans, as the results are not always the same, these new drugs are remarkably effective in the animal studies, and appear to be well-tolerated", says Mark Mattson, chief of the NIA''s Laboratory of Neurosciences.
In the study, dopamine-producing nerve cells in mice treated with pifithrin-alpha (PFT), an experimental cancer treatment, and Z-1-117, a modified version of PFT, were more resistant to being killed by environmental toxins and pesticides, such as MPTP, iron, and rotenone. These toxins are suspected of increasing the risk of Parkinson''s disease in humans and can induce symptoms of the disease in rats and mice. The drugs also helped preserve motor function in mice exposed to these compounds. The investigators suspect the drugs work because they block the action of p53, a protein that may promote the death of dopamine-producing nerve cells.
The NIA team found that p53 kills these nerve cells by causing an increase in the permeability of the membranes surrounding mitochondria, the organelles in the cell that produce energy. This increased permeability causes the release of chemicals from mitochondria that destroy the cell. The same alterations in mitochondria are believed to occur in dying nerve cells in Alzheimer''s disease and in people who have had strokes. However, PFT and Z-1-117 prevented these mitochondrial alterations.
Parkinson''s disease occurs when nerve cells in a brain region called the substania nigra die or become impaired and can no longer produce dopamine. Without dopamine, individuals can develop tremor or trembling in hands, arms, legs, jaw, and face; rigidity or stiffness of the limbs and trunk; bradykinesia, or slowness of movement; and postural instability or impaired balance and coordination. Patients may also have difficulty walking, talking, or completing other simple tasks. The disease is both chronic and progressive. Parkinson''s is not usually inherited, but incidence of the disease increases with age, with an average onset at about 60 years. It afflicts about 50,000 Americans annually.