Researchers from the Luxembourg Institute of Health (LIH) have developed a new molecule called LIH383. In a press release, they claim that this new novel molecule binds to and blocks specific opioid peptides in the brain, thus regulating the levels of opioid peptides in the entire central nervous system.
As a result, the analgesic and anti-anxiety activities brought about by these peptides are then diminished, their study finds. Opioid peptides are tiny proteins that function as neuromodulators by interacting with four 'classical' opioid receptors on the surface of CNS cells. According to the researchers, they play a crucial role in arbitrating pain relief. Additionally, it also controls emotions such as stress, anxiety, euphoria, and depression.
The head of Immuno-Pharmacology and Interactomics at LIH, Dr. Andy Chevigné, and his crew looked at findings from their previous research to aid in coming up with their recent discovery. In it, they had established the atypical chemokine receptor ACKR3 as a novel opioid receptor that binds to natural opioids and 'catches' them. This mechanism would then dampen their anti-anxiety and analgesic action.
The researchers are hopeful that their new study would bring significance to the development of a novel class of medications for depression, pain, and brain cancer treatment.
The findings of their study were published in the prestigious journal Nature Communications on June 19, 2020.
What Are Problems Related to Opioid Drug Use?
The opioid crisis has garnered much noise in the U.S. The Department of Health and Human Services says that more than 42,000 people died due to opioid use in 2016.
However, in the medical field, many patients are in dire need of these drugs to alleviate their pain. Such drugs include fentanyl, morphine, and oxycodone, which work by activating opioid receptors that prevent the transmission of natural pain signals.
The drugs also effectively alter pain perception, thus resulting in desirable pain-killing effects.
Although deemed as effective, the drugs usually lead to side effects such as dependence, tolerance, and respiratory disorders. This problem drove the researchers to search for a new way to inflect the opioid system without the complications.
In their study, the researchers have patented a new novel molecule called LIH383. They have found that it possesses the effect of making opioid peptides available for binding with classical opioid receptors in the brain.
A New Treatment for Pain and Depression is on its Way
According to Dr. Martyna Szpakowska, the co-first author of the publication, the team aimed to develop a molecule that would be able to attach to and block ACKR3.
Furthermore, they also wanted to potentiate the naturally beneficial effects of opioids on negative emotions and pain. With this in mind, they were able to come up with LIH383.
Dr. Chevigné says that as an ACKR3 modulator that collaborates and 'impedes' with ACKR3, LIH383 also holds potential in treating metastatic cancers. This, then, influences their discovery of the dual chemokine-opioid 'lurking' activity of this receptor.
He adds that they expect LIH383 to act as a precursor for developing a new class of medications against pain and depression.
The team then filed a patent application in April 2020. They claim that their findings open up alternative choices for the treatment of stress, anxiety, chronic pain, depression, and even cancer therapy.
According to a co-author of the study, Professor Markus Ollert, the director of the LIH Department of Infection and Immunity, their paper is an example of how cornerstone research can be turned into concrete applications which can benefit patients leading to improved clinical outcomes.
