Washington: Scientists have created at least five new experimental substances, based on a tiny protein found in cone snail venom that could someday lead to the development of safe and effective oral medications for treatment of chronic nerve pain. They say that the substances could potentially be stronger than morphine, with fewer side effects and lower risk of abuse.
“This is an important incremental step that could serve as the blueprint for the development of a whole new class of drugs capable of relieving one of the most severe forms of chronic pain that is currently very difficult to treat,” David Craik, Ph.D., who led the study, said.
His presentation is one of more than 10,000 scheduled to occur at the 247th National Meeting and Exposition of the American Chemical Society (ACS), the world’s largest scientific society. Craik, who is at the University of Queensland, explained that acute pain occurs when the nervous system is stimulated by a wound or injury and naturally subsides over time. In contrast, chronic neuropathic pain kicks in when the nervous system itself is damaged.
This type of pain — which is often triggered by diabetes, multiple sclerosis and other diseases — can last for months, years or even decades. Current treatments for chronic neuropathic pain have serious side effects and provide relief to only about one in every three patients, he said.
One possible solution that Craik and his colleagues are investigating comes from an unlikely source, the cone snail. Cone snails are marine animals that use venom to paralyze their prey. This venom contains hundreds of peptides (small proteins) known as conotoxins. But in humans, Craik says some of these conotoxins appear to have analgesic effects. So far, however, only one conotoxin-derived medication has been approved for human use.
This drug, ziconotide, has one big drawback: It has to be infused directly into the lower part of the spinal cord — a clearly invasive procedure. The team is working to develop a conotoxin-based drug that can be taken orally, which would be much more practical for patients. In previous research, they found a way to modify conotoxin peptides so they formed circular chains of amino acids.
As a result, the modified peptides — which are essentially tied into a loop — are extremely stable and resistant to enzymes in the body. In laboratory rats, a common stand-in for humans in many experiments, a single, small oral dose of a prototype drug based on one of these looped conotoxins appeared to significantly reduce pain, as measured by a standard protocol.
Based on this research, the scientists concluded that this prototype drug was about 100 times more potent than morphine or gabapentin, the two drugs that are considered the “gold standard” treatments for chronic nerve pain.
