By Emma Yasinski
BU News Service

Robin Williams was open about his struggles with depression and addiction, but only his family knew that he was facing another diagnosis at the time of his death – Parkinson’s disease. The seven to ten million people suffering from Parkinson’s can attest that the diagnosis is a harrowing one, foreshadowing an ever-changing cocktail of drugs, symptoms, and side effects for life. But, a new drug may have changed that- for rats at least.

Parkinson’s affects patients by killing neurons that make a neurotransmitter called dopamine in a small area, deep in the center of the brain, called the substantia nigra. Over time, patients struggle more and more to initiate movements. As the disease progresses, they may develop pain, depression, tremors, intestinal disorders, difficulty swallowing and confusion.

The most effective Parkinson’s drug on the market, levodopa, works by helping the brain replace the depleted neurotransmitter, but it cannot stop neurons from continuing to die. Doses must constantly be adjusted, which can lead to severe side effects. These side effects often need to be managed by separate drugs. Instead of struggling to initiate movement, the patient develops random, spontaneous movements. Levodopa unexpectedly stops working throughout the day, and the patient has to take more drugs with more side effects to keep it working. The patient and doctor must fight a decades-long, uphill battle to find a constantly changing combination of drugs and physical therapy.

Researchers at Emory University suspected that inflammation might be a key target for delaying the cell death in Parkinson’s disease. They developed a drug called XPro 1595 that prevents inflammation in the brain by binding to and blocking Tumor Necrosis Factor, a molecule that recruits inflammatory cells.

To test the drug, they used a well-known rat model of Parkinson’s disease in which the researcher induces the progressive, Parkinson-like cell death in the substantia nigra. Starting either 3 days or 14 days after creating the rat model, the researchers gave the rats XPro 1595 by intravenous injection in 3 day intervals.

After 35 days, the researchers evaluated the rats’ movements, levels of brain inflammation, and number of functional dopamine-producing neurons left in the substantia nigra. Rats that began dosage of the drug first (at 3 days) had the no noticeable movement disorders, minimal inflammation, and lost only 15% of their dopamine-producing neurons. The rats that began the regimen later were worse-off than the first group- with no movement problems, but some signs of inflammation and 44% of their dopamine-producing neurons gone. However, both groups were better off than the rats who received no drug at all. That group suffered motor symptoms, had the greatest signs of inflammation, and had lost 55% of their dopamine-producing neurons. Unlike current drugs, XPro 1595 was able to prevent cell death.

The human brain is capable of withstanding a lot of trauma, which makes it more difficult for doctors to diagnose Parkinson’s early. A patient rarely shows motor symptoms until 70% of these neurons are already dead. It would be too late for this drug to prevent the onset of symptoms.

That hasn’t stopped the Parkinson’s Disease Foundation from funding the next stage of research on XPro 1595, testing the drug in another well-known model of Parkinson’s in monkeys. Beth Vernaleo, Senior Manager of research programs at the Parkinson’s Foundation is confident that researchers are already beginning to identify tools for earlier diagnosis. It will still be four or five years before the drug enters clinical trials. “Our therapy is like a lady in waiting,” said Malu Tansey, Phd. a researcher involved in the study, “hoping that early identification of patients will give us an opportunity to test the efficacy of the drugs before people get motor systems.”