An experimental drug, similar to compounds used to treat diabetes, that slows the progression of Parkinson’s disease itself - as well as its symptoms - in mice has been developed by the researchers at Johns Hopkins University School of Medicine. In experiments performed with cultures of human brain cells and live mouse models, they report the drug blocked the degradation of brain cells that is the hallmark of Parkinson’s disease (lat. Parkinson scriptor morbus). The drug is expected to move to clinical trials last year. If planned clinical trials for the drug, named NLY01, are successful in humans, it could be one of the first treatments to directly target the progression of Parkinson’s disease, not just the muscle rigidity, spasmodic movements, fatigue, dizziness, dementia and other symptoms of the disorder.

According to the investigators, NLY01 works by binding to so-called glucagon-like peptide-1 receptors on the surface of certain cells. Similar drugs are used widely in the treatment of type 2 diabetes to increase insulin levels in the blood. Though past studies in animals suggested the neuroprotective potential of this class of drugs, researchers had not shown directly how it operated in the brain. To find out, the team tested NLY01 on three major cell types in the human brain: astrocytes, microglia, and neurons. They found that microglia, a brain cell type that sends signals throughout the central nervous system (lat. systematis nervosi centralis) in response to infection or injury, had the most sites for NLY01 to bind to - two times higher than the other cell types, and 10 times higher in humans with Parkinson’s disease compared to humans without the disease.

In a preliminary experiment in laboratory-grown human brain cells, the researchers treated human microglia with NLY01 and found that they were able to turn the activating signals off. When healthy astrocytes were combined with the treated microglia, they did not convert into destructive activated astrocytes and remained healthy neuroprotective cells. The team suspected that neurons throughout the body could be protected in the same way.

They explored this hypothesis by testing the drug’s effectiveness in mice engineered to have a rodent version of Parkinson’s disease. The team injected the mice with alpha-synuclein, the protein known to be the primary driver of Parkinson’s disease, and treated mice with NLY01. Similar but untreated mice injected with alpha-synuclein showed pronounced motor impairment over the course of six months in behavioral tests such as the pole test, which allows researchers to measure motor impairment such as that caused by Parkinson’s disease. However, the team found that the mice treated with NLY01 maintained normal physical function and had no loss of dopamine neurons, indicating that the drug protected against the development of Parkinson’s disease.

In a second experiment, the researchers used mice that were genetically engineered to naturally produce more human-type alpha-synuclein typically used to model human Parkinson’s disease that runs in families. Under normal conditions, these so-called transgenic mice will succumb to the disease in 387 days. However, the team found that treatment with NLY01 extended the lives of the 20 mice treated with the drug by over 120 days.

Upon further investigation, the team found that the brains of the mice treated with NLY01 showed few signs of the neurodegenerative characteristics of Parkinson’s disease. The researchers hope that NLY01 could, in a relatively short period of time, make an impact on the lives of those with Parkinson’s.