The Potential of Peptide Therapeutics in Treating Chronic Diseases

Introduction to peptide therapeutics
Advantages of peptide-based treatments
Peptide therapeutics in chronic disease management
Challenges in peptide drug developmentv Future directions in peptide therapeutics research
Case studies: Success stories in peptide therapeutics
Conclusion 
References
Further reading


The growing trend in peptide therapeutics has been growing since the isolation of insulin in 1921 and the commercial success of this peptide for diabetes.1 Medical peptides have expanded the potential of innovative medical treatments for chronic disease management, and this article will provide an overview of peptide therapeutics for chronic diseases.2

Peptide molecule. Image Credit: Kateryna Kon/Shutterstock.com

Peptide molecule. Image Credit: Kateryna Kon/Shutterstock.com

Introduction to peptide therapeutics

Peptides are short chains of amino acids, which differ from proteins due to their short length and can include two or more amino acids.3

Protein-protein interactions underlie many critical cellular functions in the body and have served as significant drug targets over the past two decades. Recent research into peptides has led to these smaller molecules being seen as strong potential candidates for targeting challenging binding interfaces.

The smaller size and flexibility of peptides have made them ideal for disrupting protein-protein interactions or binding to challenging target sites with good binding affinity and specificity.4

Innovative medical treatment strategies have led to peptide therapeutics spearheading this field, with almost 20 new peptide-based clinical trials being initiated yearly.

Additionally, there are also more than 400 peptide drugs that are under clinical development worldwide, with over 60 already being approved for clinical use in multiple countries and regions, including the United States, Europe, and Japan. 4

Advantages of peptide-based treatments

Therapeutic peptides typically behave as hormones, growth factors, neurotransmitters, ion channel ligands, or anti-infective agents; they work by binding to receptors on the cell surface and stimulate intracellular effects with high affinity and specificity with a mode of action that is similar to biologics such as therapeutic proteins and antibodies. While peptide-based treatments behave similarly to biologics, they demonstrate less immunogenicity and cost less to produce.1

Traditional small molecule drugs are also known to have low production costs and sale prices, as well as having oral route of administration and a good membrane penetration capacity.1

However, there are some advantages peptide therapeutics have over small molecule drugs, such as the small size of these molecules, which make it difficult to inhibit large surface interactions, including protein-protein interactions. Protein-protein interactions occupy a contact area consisting of 1,500-3,000 A2. However, small molecules cover less than that, with a contact area of 300-1000 A2.1

The unique physicochemical properties of peptide therapeutics enable them to be preferred over small molecule drugs as a result of their larger size, more flexible backbone, and higher specificity, which allow them to behave as strong inhibitors of protein-protein interactions in comparison.1 Additionally, with high target specificity and low toxicity, peptide therapeutics can be a safer and more effective option for treating cancer.2

Peptide therapeutics in chronic disease management

Peptide therapeutics have been used for over a century since a Canadian team of researchers discovered the potential therapeutic use of insulin for chronic disease management, such as the treatment of type 1 diabetes.2

Peptide therapy for chronic illness - the timing can make all the difference

Insulin is a classic example of the use of an endogenous hormone as a therapeutic treatment, with it being the first peptide drug to be used clinically as well as being the most commercially successful.5 After being first isolated in 1921 and further developed, it was available for patients diagnosed with diabetes mellitus a year after being isolated.1

Peptide therapeutics can be applied to cancer in four main ways, including (i) using radioisotopes, dyes, or as probes for tumor diagnosis and imaging; (ii) using peptide-coupled nanomaterials for tumor therapeutics; (iii) using peptide vaccines in order to activate the immune system to prevent cancer development; (iv) using peptides alone to develop targeted drugs.

Octreoscan is a Food and Drug Administration (FDA) approved probe consisting of a radiolabeled conjugate of a somatostatin-like peptide used for tumor imaging in neuroendocrine and lung cancer.1

Challenges in peptide drug development

Peptide therapeutics have two main intrinsic challenges, including membrane impermeability and poor in vivo stability.1

Peptides consist of weak membrane permeability, with multiple factors such as peptide length and amino acid composition. Peptides are not usually able to cross the cell membrane to target intracellular targets, and this can limit their application in drug development.

A 2018 study reported more than 90% of peptide therapeutics in active clinical development worked by targeting extracellular targets such as G-protein coupled receptors and gonadotrophin-releasing hormone.[1]

Another significant challenge is that peptides have poor in vivo stability. Natural peptides consist of amino acids that are joined with amide bonds; however, as they do not have secondary or tertiary structures, they lack the same stability. Additionally, amide bonds can be hydrolyzed or destroyed easily by enzymes in vivo due to environmental exposure. These chemical properties make peptides characteristically unstable both chemically and physically, as well as having a short half-life and being eliminated quickly in vivo.1

Strategies to overcome the challenges of peptide therapeutics include direct optimization of the therapeutic compound properties, which have a knock-on effect on the chemical structure, drug formulation, and delivery approaches. This can aid in overcoming some challenges without modifying the peptide structure.6

Case studies: Success stories in peptide therapeutics

Peptide therapeutic research into chronic disease management led to the development of glucagon-like peptide-1 (GLP-1), which is produced by ileal endocrine cells and can stimulate insulin secretion.7

In healthy individuals, GLP-1 is usually produced after eating and reduces glucose concentrations through stimulating insulin secretion and suppressing glucagon release.8 There have been extensive efforts to use GLP-1 for the treatment of chronic disease management in type 2 diabetes mellitus due to its glucose-reducing effects; GLP-1 has been successfully marketed for this application since.7

GLP-1 can also be used to treat obesity, with its receptor agonists being found to inhibit food intake. In a mice study, GLP-1 receptor-knockout mice were observed not to become obese; additionally, injecting GLP-1 into the peripheral or central nervous system has been shown to reduce food intake in rats effectively.7

Future directions in peptide therapeutics research

Global industry analysis on peptide therapeutics has predicted a compound annual growth rate (CAGR) of 9.1% from 2016 to 2024. The growth in this field has been attributed to increased incidence of metabolic disease and cancers, with the two top-selling drugs for metabolic disease, including liraglutide and glucagon-like peptide, having a minimum of two billion USD in sales per annum.4

Peptide drugs have grown significantly since their conception and can be used for more than just mimicking hormones or being composed of natural amino acids. The potential of peptide therapeutics is monumental, with promising treatments for many diseases. An example includes enfuvirtide, which mimics HIV proteins and is used in combination therapy for the treatment of HIV-1, while teduglutide is a glucagon-like peptide 2 analogue that is used for the treatment of short bowel syndrome.1

Conclusion

With therapeutic applications of peptides growing in interest and 26 peptide drugs gaining approval between 2016 and 2022, it is almost a certainty that more peptide drugs will gain FDA approval over the coming years. More than 200 peptide therapeutics are in clinical development, and another 600 are in preclinical studies.2

The growth of peptide therapeutics is significant for improving patient outcomes in various diseases, especially cell-penetrating peptides that are currently under investigation as drug delivery tools for anticancer, antiviral, and antibacterial therapeutics.2

References

  1. Wang L, Wang N, Zhang W, et al. Therapeutic peptides: Current applications and Future Directions. Signal Transduction and Targeted Therapy. 2022;7(1). doi:10.1038/s41392-022-00904-4
  2. Rossino G, Marchese E, Galli G, et al. Peptides as therapeutic agents: Challenges and opportunities in the Green Transition Era. Molecules. 2023;28(20):7165. doi:10.3390/molecules28207165
  3. Peptide Definition. Nature news. Accessed March 10, 2024. https://www.nature.com/scitable/definition/peptide-317/.
  4. Lee AC-L, Harris JL, Khanna KK, Hong J-H. A comprehensive review on current advances in peptide drug development and Design. International Journal of Molecular Sciences. 2019;20(10):2383. doi:10.3390/ijms20102383
  5. Muttenthaler M, King GF, Adams DJ, Alewood PF. Trends in peptide drug discovery. Nature Reviews Drug Discovery. 2021;20(4):309-325. doi:10.1038/s41573-020-00135-8
  6. Lamers C. Overcoming the shortcomings of peptide-based therapeutics. Future Drug Discovery. 2022;4(2). doi:10.4155/fdd-2022-0005
  7. Gao Y, Yuan X, Zhu Z, Wang D, Liu Q, Gu W. Research and prospect of peptides for use in obesity treatment (review). Experimental and Therapeutic Medicine. 2020;20(6):1-1. doi:10.3892/etm.2020.9364
  8. Meier JJ. GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus. Nature Reviews Endocrinology. 2012;8(12):728-742. doi:10.1038/nrendo.2012.140

Further Reading

Last Updated: Jun 4, 2024

Marzia Khan

Written by

Marzia Khan

Marzia Khan is a lover of scientific research and innovation. She immerses herself in literature and novel therapeutics which she does through her position on the Royal Free Ethical Review Board. Marzia has a MSc in Nanotechnology and Regenerative Medicine as well as a BSc in Biomedical Sciences. She is currently working in the NHS and is engaging in a scientific innovation program.

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