Peptide Therapy: The Future of Targeted Treatment?

Marzia Khan - Since 1921, when the first therapeutic peptide, insulin, was synthesized, many peptide-related accomplishments have reverberated throughout the industry, with more than 80 peptide drugs being approved globally.

Peptide-based drug development has been a popular area of pharmaceutical research due to many peptides having specific physiological activities in the human body, such as oxytocin, vasopressin, and gonadotrophin-releasing hormone.

The advantages of peptide therapy consist of their deep penetration into tissues such as the skin and intestines, compared to larger biomolecules, including antibodies, which enable a faster entrance into the bloodstream.

Additionally, their low immunogenicity and high target specificity are superior to small drug molecules, which only target 2-5% of the human genome. In contrast, peptides have higher selectivity for specific protein targets.

How peptide therapy works

Peptide drugs can work in a versatile manner, acting as hormones, growth factors, ion channel ligands, neurotransmitters, or anti-infective agents. They bind to cell surface receptors and stimulate intracellular effects with both high specificity and affinity.

The mode of action for therapeutic peptides is similar to biologics such as therapeutic antibodies and proteins, with the advantage of having less immunogenicity and production expenditure.

This growing area of pharmaceutical development led to 26 peptides being approved as drugs between 2016 and 2022 by the Food and Drug Administration (FDA), with more than 315 new drugs also being approved in that same time period.

The growth in this area has translated to more than 200 peptides being in current clinical development and another 600 peptides in preclinical trials.3 G17DT is an example of a therapeutic peptide that is currently undergoing clinical trials and indicates various forms of cancer.

Advantages of peptide therapy over traditional treatments

As previously mentioned, the advantages of peptide therapy over conventional treatments and small molecules are deeply rooted in properties such as high specificity, high biological activity, high penetrative ability for membranes, and low cost.

This may lead to faster development timelines compared to small-molecule drugs that go through significant trial and error.

Additionally, the increased specificity of peptide therapy can also lead to reduced side effects, which is pertinent in cancer therapeutics, such as chemotherapy, that can cause systemic adverse effects.

The potential for utilizing peptide therapies for personalized medicine applications is also vast, with specific peptide sequences being screened and synthesized for targeting mechanisms and various cell surface receptors in many different diseases and disorders. In this way, peptide-based drug development may be significant for the future of targeted treatment.

Challenges and limitations

Challenges of peptide-based drug development consist of stability, toxicity, and immunogenicity. However, strategies for enhancing peptide stability include integrating D-amino acids or α-aminoxy amino acids, which modifies the backbone chemistry and cyclization.

Additionally, incorporating these into the manufacturing process can decrease storage stabilities by enabling peptides to be more sensitive to both pH and temperature, which can cause easy degradation.

Regulatory hurdles for peptide-based drugs are also a challenge, with only 4% of FDA-approved peptide/protein drugs utilizing oral administration, which is the delivery route with the highest patient adherence rate.

However, oral administration can be challenging in itself, with barriers such as the intestinal epithelial membrane barrier and mucus barrier, which may prevent drugs from penetrating and absorbing effectively.

Future directions in peptide therapy

With novel technologies such as artificial intelligence (AI) and machine learning, along with peptide therapeutic research, the future of drug development may advance significantly, reducing costs, enhancing personalized, targeted disease treatment, and decreasing toxicity.

Traditional peptide discovery methods are limited in their ability to explore the large chemical arena of potential peptide sequences, which are time-consuming, expensive, and inefficient at finding promising targets.

This process can be accelerated with AI through efficient analysis of diverse datasets, including but not limited to genomic and clinical data and protein structures.

Interestingly, deep learning and AI methods have discovered novel functional and antimicrobial peptides (AMPs) from many sources, such as the human proteome and microbiome; this is significant for developing alternative antibacterial drugs that will be effective against the rapid growth of antibiotic resistance.

Overall, the integration into the drug discovery process can exponentially reduce the time and cost of identifying and developing new peptide therapies.

What this means for healthcare and drug development

The development of new drugs and strategies, such as peptide therapies, is critical for healthcare, with aims to identify and characterize substances that hold the potential for improving patient outcomes and addressing unmet medical needs for a number of disease areas.

With personalized medicine being at the forefront of the future of targeted therapies, hundreds of peptides are currently being researched in preclinical and clinical trials. This area is expected to grow exponentially, attracting both investment and research efforts.

In 2017, peptide drug sales reached US$20 billion, and this was expected to grow to more than US$50 billion by 2024; the market size is also likely to increase from US$25.3 billion in 2024 to US$41.7 billion by 2030, with a Compound Annual Growth Rate (CAGR) of more than 8%. Source - news-medical.net

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Evidence

Peptides may be useful tools in select clinical contexts, but claims of universal rejuvenation are ahead of the evidence.