Key takeaways about targeted oral peptides
- Peptides are short chains of amino acids that assist in a variety of functions, including building and repairing muscle, creating hormones and enzymes, acting as messengers and supporting a healthy immune system.
- Targeted oral peptides are modified peptides delivered to patients in a pill form that act on specific parts of the body to treat a disease or condition.
- Targeted oral peptides are not the same as the largely unregulated, over-the-counter peptide products that are touted on social media as the key to exercise recovery, longevity and other areas of wellness.
- Because targeted oral peptides are designed to precisely target specific cells in inflamed tissues, experts say they may have fewer unwanted side effects than medication delivered by injection or infusion.
- Targeted oral peptides are currently used to treat diseases such as plaque psoriasis, and researchers are exploring their potential use for other diseases and conditions.
At their most basic, peptides are short chains or arrangements of amino acids, which are the building blocks of protein. Peptides have multiple normal biological roles: They provide amino acids for building and repairing muscle, act as hormones and signaling molecules, form the building blocks of enzymes and contribute to immune function.
The body naturally makes thousands of different peptides that help regulate various physiological processes. “Scientists have learned to create modified peptides to focus on specific disease pathways in the body,” says Beverly Knight, an Immunology Therapeutic Area Lead for Pharmacokinetics at Johnson & Johnson.
Peptide medications have historically been difficult to deliver orally because they are rapidly broken down in the gastrointestinal (GI) tract and aren’t well absorbed, which is why many are given by injection or infusion.
Enter the development of targeted oral peptides, which are designed to be taken by mouth and act on targets within tissues or organs to treat various diseases and conditions.
Targeted oral peptides are a type of medication; they are not the same as the trendy peptide products sold online or at wellness clinics, which claim to boost athletic performance, reduce inflammation and help with other areas of health.
Thanks to their precision in zeroing in on specific cells and the convenience oral delivery may offer to patients, targeted oral peptides could potentially be used for a wider range of diseases. We asked Knight to help explain how targeted oral peptides work, the diseases they’re currently approved to treat and why they could help usher in a more personalized era of medicine.
Targeted oral peptides: How do they work?
To understand what makes targeted oral peptides unique, it helps to look at two major categories of drugs: small-molecule drugs and large protein-based drugs.
“Small-molecule drugs are chemically synthesized molecules that are very small in size, can be given orally and are really well absorbed,” says Knight. “Once they’re in the bloodstream, they circulate widely throughout the body. This can be useful, but it can also mean that the drug interacts with unintended targets in the body or with other drugs a patient might be taking.”
On the other side of the spectrum are large protein-based drugs, which bind very selectively to a particular target in the body. But because they are unstable in the GI tract and too large to be absorbed, oral delivery is not possible. Therefore, these medications need to be injected or infused. Due to their large size, they also don’t distribute well to the rest of the body.
“Peptides fall somewhere in the middle,” says Knight. “They can very specifically reach one target, but most of the time you need to give them via an intravenous or subcutaneous dose. You usually can’t give them orally.”
However, researchers have recently succeeded in their efforts to create modified peptides that can be given orally. “This allows us to distribute the medication to all tissues like a small-molecule drug but also have the targeted specificity of a large protein-based drug,” says Knight.
Targeted oral peptides are unique in that just a small amount of the drug is absorbed from the dose that is given. That little amount can go to the tissues where it needs to go and hit the target it needs to hit at a sufficient level to treat the disease.
How are targeted oral peptides engineered to impact specific cells and organs?
It starts with experimentally visualizing a 3D image of the target the scientists want the drug to bind to. “We try to dock the peptide into this 3D mathematical model until we get a perfect fit—like a key in a lock,” says Knight.
Next, the structure of the peptide is modified to help it function like a drug. Amino acids may be swapped for more stable versions, and the linear amino acid chains can be cyclized—or joined into a circle. “This makes the molecule more resistant to breakdown once it hits the GI tract and more easily absorbed,” says Knight.
“Targeted oral peptides are unique in that just a small amount of the drug is absorbed from the dose that is given,” says Knight. “That little amount can go to the tissues where it needs to go and hit the target it needs to hit at a sufficient level to treat the disease.”
“Any peptide that’s not absorbed just travels through the GI tract unchanged and comes out the other end,” explains Knight. “And the drug that is in circulation is cleared by the kidney.”
The safety and efficacy of targeted oral peptides
This combination—selectively hitting targets in the body coupled with a small amount of the drug in circulation—may offer advantages when it comes to safety, efficacy and tolerability.
Because these molecules are engineered to bind tightly to a particular target rather than interact with numerous targets throughout the body, it could mean fewer unwanted effects, says Knight. “And since you don’t need a lot of the drug circulating through the body to work, smaller concentrations of medication likely lead to fewer side effects.”
Clinical safety data are especially key in the current era of unregulated peptides. Clinical trials like the ones targeted oral peptides go through involve thousands of participants and follow those patients for a year or longer, providing extensive information about a drug’s optimal dosing and safety profile before it is reviewed and approved by regulatory authorities and reaches patients.
The future for targeted oral peptides
Researchers are currently exploring whether these medications could be used for a wider range of diseases, particularly immune-mediated diseases such as psoriatic arthritis, inflammatory bowel disease and rheumatoid arthritis.
The growing use of artificial intelligence (AI) may expedite these discoveries, says Knight. For example, AI could assist with the aforementioned mathematical models and help design and identify peptides with drug-like properties. “The hope is that AI will accelerate peptide design and the development of future drugs,” she says.
And while creating a targeted peptide that could be taken orally was a huge advance in the space, researchers continue to experiment with absorption enhancers that would help them work even better, as well as entirely new delivery systems.
“I think within 10 years, we could have multiple targeted peptides on the market that are given orally to treat different diseases,” says Knight. “That’s my dream.”
