Cases of Parkinson’s disease have doubled in the last 25 years, according to figures from the World Health Organization. For decades, the scientists have investigated what triggers this disorder to mitigate its symptoms and anticipate its onset. Now, a series of experimental therapies are laying the groundwork for potentially reversing the condition, which affects nearly 10 million people worldwide and can generate costs of approximately $10,000 per patient per year, when considering direct and indirect medical expenses.
Parkinson’s disease is a degenerative neurological disorder in which cells that produce dopamine in the brain die, causing symptoms such as tremors, muscle stiffness, slowness of movement, and alterations in balance. So far there is no cure, and treatments are limited.
Kay Double, a professor at the University of Sydney’s School of Medical Sciences, has been researching the biological mechanisms underlying this disease for more than a decade, with the aim of finding ways to slow or even halt its progression.
In 2017, he led a study that identified for the first time an abnormal form of a protein called SOD1 in Parkinson’s patients. Under normal conditions, this protein acts as an antioxidant enzyme, protecting brain cells from damage caused by free radicals, highly reactive molecules that contain oxygen and can deteriorate cells if not properly neutralized. Free radicals are produced by natural bodily processes as well as by external factors, like diet, smoking, and exposure to pollution.
In people with Parkinson’s disease, SOD1 suffers alterations that prevent it from fulfilling its protective function, with it instead accumulating in the brain and causing neuronal damage, according to the findings of Double’s team.
Based on these results, the team then conducted further research, with results suggesting that copper supplementation in the brain could be an effective way to slow and even reverse the symptoms of Parkinson’s (copper is crucial to SOD1’s function). To test this hypothesis, they evaluated the efficacy of a drug called CuATSM, designed to cross the blood-brain barrier and deliver copper directly to brain tissue.
This experiment, written up and published in Acta Neuropathologica Communications, was divided into two phases. The first was to determine the optimal dose of the drug to induce a response in the brain. To find this, CuATSM was administered daily for three weeks to 27 eight-week-old wild-type mice, with concentrations of copper and other metals then measured in the mice’s tissues. This revealed that 15 milligrams per kilogram was the ideal dose to effectively increase the levels of copper in the brain.
In the second stage, this dose was applied to 10 mice genetically modified to develop Parkinson’s-like symptoms. The animals were divided into two groups: one received CuATSM daily for three months, while the other received a placebo without the active ingredient.
The results showed that the mice treated with the placebo experienced a deterioration in their motor skills. In contrast, those that received the copper supplement showed no alterations in their movement. It appears the treatment corrected the dysfunctions of SOD1 and restored its protective properties. In the mice receiving the copper treatment, dopamine neurons were preserved in an area of the brain called the substantia nigra, an area essential for the control of movement, coordination, learning, and certain cognitive functions.