Experimental drug stops progression of Parkinson's disease and symptoms in mice

Johns Hopkins researchers say that they have developed an experimental drug similar to compounds used to treat diabetes that slows the progression of Parkinson's disease and its symptoms in mice

they report that the drug, called NLY01, has blocked the breakdown of brain cells that is the hallmark of Parkinson's disease. The drug is expected to go to clinical trials this year.

"It surprisingly protects target nerve cells," says Ted Dawson, director of the Institute of Cell Engineering and professor of neurology at the Johns Hopkins University School of Medicine.

Dawson explains that if the clinical trials planned for NLY01 succeed in humans, it could be one of the first treatments to directly target the progression of Parkinson's disease, not only muscle rigidity, spasmodic movements, fatigue, vertigo and dementia. other symptoms of the disease.

If the clinical trials planned for NLY01 succeed in humans, it could be one of the first treatments to directly target the progression of Parkinson's disease, not just the symptoms of the disease.

A report of the results of the study was published last month in Nature Medicine .

According to the researchers, NLY01 works by binding to glucagon-like peptide-1 receptors on the surface of certain cells. Similar drugs are widely used in the treatment of type 2 diabetes to increase insulin levels in the blood. Although previous studies have suggested the neuroprotective potential of this clbad of drugs, researchers have not shown directly how it works in the brain.

To find out, Dawson and his team tested NLY01 on three major cell types in the human brain: astrocytes, microglia and neurons. They found that microglia, a type of brain cell that sends signals into the central nervous system in response to an infection or injury, had the most sites for NLY01 to bind to twice as much as other types of cells and 10 times more

Dawson and his team knew that microglia secrete chemical signals that transform astrocytes – star-shaped cells that help neurons communicate with their neighbors – into aggressive "activated" astrocytes, which gnaw the connections. between brain cells, causing the death of neurons. They speculated that NLY01 could stop this conversion.

"The activated astrocytes we focus on are going on a revolt against the brain," says Dawson. "This structural degradation contributes to dead areas of brain tissue in people with Parkinson's disease, the idea being that if we could find a way to calm these astrocytes, we could slow down the progression of Parkinson's disease. "

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

They explored this hypothesis by testing the efficacy of the drug in mice designed to have a rodent version of Parkinson's disease.

The brains of the NLY01-treated mice showed little evidence of the neurodegenerative features of Parkinson's disease.

In one experiment, the Dawson team injected mice with alpha-synuclein, the protein known to be the main driver of Parkinson's disease, and treated mice with NLY01. Similar untreated mice injected with alpha-synuclein showed a pronounced motor impairment over the course of six months in behavioral tests used to measure motor disorders such as those caused by Parkinson's disease. However, the Dawson team found that mice treated with NLY01 maintained normal physical function and showed no loss of dopaminergic neurons, indicating that the drug protected against the development of Parkinson's disease.

In a second experiment, the Dawson team used mice genetically engineered to naturally produce more human-type alpha-synuclein typically used to model human Parkinson's disease that is prevalent in families. Under normal conditions, these so-called transgenic mice will succumb to the disease in 387 days. However, the Dawson team found that treatment with NLY01 prolonged the life of the 20 mice treated with the drug by more than 120 days.

After further investigation, Dawson's team found that the brains of mice treated with NLY01 The neurodegenerative features of Parkinson's disease

Parkinson's disease is a progressive disorder of the nervous system which affects about 1 million people in the United States, according to the Parkinson Foundation. Early symptoms include tremors, sleep disturbances, constipation, and movement or gait disturbances, which eventually give way to more serious symptoms such as loss of motor function and ability to speak and dementia. Most people start having symptoms in their 60s, but cases have been reported in 2-year-olds.

Drugs similar to NLY01 have already been approved by the FDA for the treatment of type 2 diabetes, including exenatide, lixisenatide, liraglutide and dulaglutide, each of which can cost around $ 2,000 for a 90-day supply.

Dawson warns that the NLY01 should always be tested for safety and effectiveness in people, but based on the safety profile of other similar drugs, it does not foresee any major impediments to its use in humans. He adds that he and his team have reason to hope that NLY01 could, in a relatively short period of time, have an impact on the lives of people with Parkinson's disease.