Parkinson's patients can suffer from a range of symptoms affecting their movement including something known as dyskinesia, which causes involuntary motion of body parts and makes everyday tasks a tricky undertaking. A new study exploring the potential of an experimental drug to reduce its severity has returned some promising results, with monkeys undergoing treatment exhibiting much improved symptoms thereafter.
Dyskinesia is not a direct symptom of Parkinson's disease itself. Rather, it can arise as a side effect of a common Parkinson's drug called levodopa, which is transported to the brain and converted into dopamine. A deficiency in dopamine cells is considered a key driver of Parkinson's disease, and drugs like levodopa can be used to address the slide.
But around half of all Parkinson's sufferers using levodopa will experience dyskinesia after five years of treatment, while up to 80 percent will experience the side effect after ten. In the new study, which was funded by Parkinson's UK and carried out by US biotech firm Neurolixis, scientists set out to explore how dyskinesia could be treated with an experimental drug called NLX-112.
NLX-112 targets the elements of the brain's serotonin system that scientists believe drive dyskinesia by releasing dopamine in an irregular fashion. By limiting the ability of these cells to release fluctuating amounts of dopamine, NLX-112 is designed to bring some stability to the mix and ease the erratic nature of dyskinesia symptoms.
The scientists conducted experiments on marmosets with both Parkinson's-like symptoms and dyskinesia following continuous treatment with levodopa. NLX-112 was tested on its own as well as in combination with levopoda, and the team found that it successfully reduced dyskinesia, without significantly impacting the effectiveness of levodopa.
That is viewed as a huge plus, because similar drugs have shown an ability to suppress dyskinesia, but hamper the effectiveness of levodopa at the same time. When NLX-112 was used exclusively, it also improved movement problems, all on its own.
"This promising research on NLX-112 offers hope that we can find a treatment that can tackle dyskinesia, which can make everyday tasks, such as eating, writing and walking, extremely difficult," says Dr Arthur Roach, Director of Research at Parkinson's UK. "People with Parkinson's tell us it is one of the most critical issues that impacts quality of life so we're delighted that this project is progressing so positively."
NLX-112 has been safely tested on around 500 human subjects so far, including trials to treat pain in diabetics. The researchers are therefore hopeful of moving ahead to phase 2 clinical trials involving humans with Parkinson's, with plans to commence before the end of 2020.
"We are excited that NLX-112 has shown such positive results in reducing dyskinesia in marmosets," says Adrian Newman-Tancredi, PhD, co-founder and CEO at Neurolixis. "If the striking preclinical data are reproduced in clinical trials, NLX-112 could significantly alleviate the troubling dyskinesia that prevent many Parkinson's patients from performing routine daily tasks, thereby improving their quality of life."
The research was published in the journal Neuropharmacology.
Source: Parkinson's UK via EurekAlert
