Short peptides are promising therapeutic agents that outperform most traditional drugs when it comes to treating a wide range of diseases with minimal risks of side effects. However, for a long time, their relevance was suffering a major setback — the impossibility of taking them orally. Fortunately, there’s been a breakthrough, and it could open a new avenue for treatment in modern medicine.
A new method of testing and creating short peptides
Researchers at EPFL, have discovered a new method of testing short peptides to find out those that can survive gastrointestinal (GI) degradation, and go on to fulfill their therapeutic objective. The testing method has also made it possible to create new short peptides that can treat specific diseases in highly targeted areas of the body.
Before the breakthrough, incorporating non-natural amino acids to synthesize the biomolecules was a huge limitation. Pharmaceutical industries had to utilize active ingredients extracted from cells grown by fermentation, and this was not only relatively difficult but expensive as well.
Currently, short peptide products represent a billion-dollar market, and based on upward trends, and the rate it is going, it is projected to exceed $60 billion by the year 2026. With the new method of testing and creating short peptides, there’s no telling how much the industry will grow.
What are short peptides?
Short peptides are polymers found in living organisms that consist of 2-4 chains of amino acids. They regulate biological activities and prove safe and useful in the treatment of a wide range of diseases. Chains of amino acids longer than 50 are called proteins. Proteins perform a lot of functions, including the building and repairing of tissues, and the creation of hormones, enzymes, and other essential body chemicals.
However, short peptides are considered very special and relevant to modern-day medicine. This is as a result of their relatively smaller size that enables them to penetrate the skin, and the walls of the small intestine more efficiently. Compared to conventional medicines, these biomolecules have a better safety profile. They do not accumulate in the liver, kidney, and other sensitive organs, but are recycled instead. Generally, they pose minimal risks of toxic side effects.
EPFL researchers and their way of making short peptides
From slowing down aging to controlling sugar metabolism, and facilitating muscle building, among others, short peptides have proven highly resourceful since their discovery. However, for a long time, their development was hampered by the fact that they could not be taken orally.
Upon administration, the stomach acid breaks down the bonds that hold the peptides and protein chains together, rendering them ineffective. Consequently, many scientists sought for a relatively easy and cost-effective method of testing and creating them. EPFL researchers made a breakthrough. They discovered a new method of testing and making short peptides that is not only efficient but cost-effective. They achieved this by following up on their previous research on double-bridged peptides which happen to be stronger, but still unstable for practical use.
From a billion random peptide sequences, one by one, the research team combined them with chemical bridges to make the short peptides more resilient. After this, they exposed the new formulations to the digestive enzymes of cows to find if they survived the gastrointestinal tract. And for everyone that did, another test was carried out to find out if they still possessed their therapeutic effects. The test involved dipping different proteins in a pool of the resilient peptide molecules. If a peptide sticks to a protein, it means that it’ll target that same protein inside the body.
Eventually, the researchers stumbled upon a short peptide molecule that is both stable and medically potent. Meaning that it could survive the GI, filter into the bloodstream, and still carry out its intended therapeutic function. This new short peptide impedes thrombin — an enzyme associated with blood clotting. As a result, it is effective against thrombosis.
The animal tests carried out on mice, confirmed the findings. In the test, the short peptide administered in pill form escaped breakdown by the enzymes in the GI, remained potent, and filtered into the mice’s bloodstream in small amounts. The test suggests that the specific short peptide can be administered orally and that it’ll target that part of the body. This is notwithstanding the fact that only 30% of the drug made it to the blood.
Christian Heinis, leader of the study, has indicated the team’s plan to focus on inflammatory diseases such as ulcerative colitis, and Crohn’s disease, which affects the gastrointestinal tract. These diseases affect patients worldwide, and up until the breakthrough, had no orally-administered drug available.
Research is ongoing, and hopefully, more orally-administered peptide-infused products will be developed to treat many more diseases.