Parkinson’s occurs when nerve cells in the brain die. This light micrograph shows mouse neurons labeled with fluorescent proteins to distinguish between cells at different depths
Dr. Gopal Murthy/Science Photo Library
A mystery drug has shown promise for Parkinson’s disease, improving the mobility and balance of mice with Parkinson’s-like symptoms. The drug works by boosting the brain’s waste disposal system to remove clumps of toxic proteins, but the researchers behind this work are not yet revealing what the treatment is, they only refer to it as Compound X.
“Our goal is to do some (intellectual property) protection around the repurposing of Compound
Parkinson’s disease, which More than 10 million people are affected worldwideIt is associated with the loss of nerve cells in parts of the brain that help control movement. It is thought to be caused by an incorrect form of a protein called alpha-synuclein. Studies show that it Accumulates due to a malfunction in the brain’s waste disposal systemWhich is known as the glymphatic system. But it was not clear whether boosting this system reduced symptoms.
To find out, Yan and his colleagues turned to a new mouse model of Parkinson’s. The approach, which they developed earlier, involves repeatedly instilling a few drops containing misfolded alpha-synuclein into the noses of mice. From there, the protein spreads in and around the brain, causing serious mobility problems. This replicates Parkinson’s more accurately than other models where symptoms are induced through brain damage, such as exposure to toxins, Yan says, without mimicking the alpha-synuclein clumps we see in people. They presented the study findings at the Oxford Glymphatic and Brain Clearance Symposium in the UK on April 1.
The team gave weekly doses of alpha-synuclein to 20 mice for four months. Over two months, half the mice were given Compound X, a drug approved by the US Food and Drug Administration, four times a week. The group also received a chemical called methylcellulose which helps the drug dissolve. Yan says Compound
The remaining rats received methylcellulose alone, serving as a control. The degree of Parkinson’s progression in the mice was roughly equivalent to when people with Parkinson’s disease are in the early stages of the condition, where they may experience changes in smell or sleep, Yan says.
All rats then completed a mobility test in which they were placed on top of a thin pole and had to carefully turn their bodies to get down. In the Compound X group, 80 percent of rats completed the task successfully, while only 10 percent of rats in the control group completed the task successfully.
Another movement task required rats to balance on a rotating rod for 5 min. Nearly all of those who received Compound
Further analysis revealed that Compound It also reduced the number of alpha-synuclein clumps in the mice’s motor cortex – a brain area that controls movement – ​​by an average of 40 percent more than methylcellulose alone.
“I think it’s very important,” says wenzhen duan At Johns Hopkins University in Maryland. “We need compounds or treatments that can delay or slow the disease. The treatments available in the clinic temporarily relieve symptoms, (but) none of them actually slow or reverse the disease.”
The team hopes to get regulatory approval within the next year to test the drug in people with early-stage Parkinson’s. “The long-term objective would be to treat people in the early stages of the disease because that will have the greatest benefit,” says Yan.
Subject:
