Introduction
How peptide therapy works
Key areas of peptide therapy research
Advantages of peptide therapy over traditional treatments
Challenges and limitations
Future directions in peptide therapy
What this means for healthcare and drug development
References
Further reading
Peptide therapy consists of a unique pharmaceutical class of agents that are constructed of a range of organized amino acids, which usually have a molecular weight of 500-5,000 Da.1
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Precision vs. Personalized Medicine
Introduction
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.1
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.1
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.1
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.2
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.1
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.1
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.1
Key areas of peptide therapy research
Oncology
Investigational peptide therapies in cancer and targeted drug delivery are essential, with direct drug delivery into tumor cells mitigating off-target effects. This key characteristic causes decreased quality of life in patients receiving chemotherapy.4
Peptide therapeutics are also being investigated for their capacity to disturb and disrupt critical tumor anti-apoptosis proteins, as well as their ability to inhibit tumor drug resistance mechanisms through targeting related protein-protein signaling pathways.4
An example of a well-researched related peptide is Bim BH3, which stimulates apoptosis using the regular protein Bcl-2. With cancer cells varying in their cell surface receptors, even within the same organ, precision targeting mechanisms for these are critical, with peptide therapies being the ideal solution due to the capacity to screen and synthesize specific peptide sequences fit for purpose.4
Metabolic Disorders
Metabolic homeostasis is critical for all life activities, which is enabled through several biological pathways. The disruption of metabolic homeostasis can lead to the development of metabolic diseases, which are slow-forming and challenging, with many complex etiologies.
Approximately 35% of adults and 50% of the aging population have metabolic diseases within the United States.5
The most common metabolic diseases include, but are not limited to, obesity, diabetes, non-alcoholic fatty liver disease, metabolic function-associated fatty liver disease, and cardiovascular diseases.5
The peptide liraglutide, known under Saxenda, as well as semaglutide, known more commonly under the name Ozempic, are two obesity peptide drugs. Liraglutide consists of an agonist for the GLP-1 receptor, which has physiological effects such as increasing insulin release, reducing glucagon release, and decreasing hunger sensations.5
Studies on incorporating liraglutide into a lifestyle intervention experiment found that this peptide therapeutic caused an average weight loss of 4-6 kg within one year. Semaglutide also has similar effects to liraglutide, impacting hypoglycemia and weight loss.5
Neurodegenerative Diseases
Within neurodegenerative diseases that are characterized by gradual neuron loss in the brain, resulting in death, peptide therapy research may be significant in advancing insufficient available treatments to manage these diseases.6
Approximately 25% of global deaths and disabilities are caused by brain-associated diseases, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis (ALS).6
Peptide therapy research can be used to investigate the properties of misfolded proteins/peptides within neurodegenerative disorders that lead to disrupted signaling in neurons and their eventual death.6
Peptide vaccines, which have been predominantly researched for fighting against influenza, also include UB-311 and were found to stimulate improvements in cognition in patients with early-stage Alzheimer’s dementia.6
Other peptide inhibitors being researched for neurodegenerative diseases include (i) neurotrophins, (ii) NAPVSIPQ, (iii) and vasoactive intestinal peptides (VIP).6
Regenerative Medicine
Finally, with the wound healing process consisting of complex and multi-stage steps, such as hemostasis, inflammation, proliferation, and remodeling, the use of peptide research may be crucial in advancing this process, especially for those suffering from chronic wounds secondary to diseases.7
Peptide-based wound dressings may provide a novel approach to wound management, with many natural peptides, such as RL-QN15, derived from secretions in the skin, that function to accelerate the wound healing process.
Additionally, other natural peptides, such as fibroblast growth factor and epidermal growth factor, function to improve wound healing processes, including proliferation and tissue remodeling.7
The Future of Medical Treatments: Personalized Medicine.
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.6
This may lead to faster development timelines compared to small-molecule drugs that go through significant trial and error.9
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.4
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.4
What's Next for Semaglutide? Beyond Diabetes and Weight Loss
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.6
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.8
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.9
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.9
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.9
Overall, the integration into the drug discovery process can exponentially reduce the time and cost of identifying and developing new peptide therapies.9
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.9
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.9
In 2017, peptide drug sale reached $20 billion, and this was expected to grow to more than $50 billion by 2024; the market size is also likely to increase from $25.3 billion in 2024 to $41.7 billion by 2030, with a Compound Annual Growth Rate (CAGR) of more than 8%.9
How is AI Transforming Drug Discovery?
References
- 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.
- Barman P, Joshi S, Sharma S, Preet S, Sharma S, Saini A. Strategic Approaches to Improvise Peptide Drugs as Next Generation Therapeutics. International Journal of Peptide Research and Therapeutics. 2023;29(4). doi:10.1007/s10989-023-10524-3.
- 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.
- Warthen JL, Lueckheide MJ. Peptides as Targeting Agents and Therapeutics: A Brief Overview. Biomacromolecules. 2024;25(11):6923-6935. doi:10.1021/acs.biomac.4c00518.
- Teng B, Li J, Ren P. Peptide Drugs Application in Metabolic Diseases and Discovery Strategies. Journal of Holistic Integrative Pharmacy. 2022;3(1):24-31. doi:10.1016/s2707-3688(23)00063-8.
- Baig MH, Ahmad K, Saeed M, et al. Peptide Based Therapeutics and Their Use for the Treatment of Neurodegenerative and Other Diseases. Biomedicine & Pharmacotherapy. 2018;103:574-581. doi:10.1016/j.biopha.2018.04.025.
- He X, Wu W, Hu Y, et al. Visualizing the Global Trends of Peptides in Wound Healing Through an In‐Depth Bibliometric Analysis. International Wound Journal. 2023;21(4). doi:10.1111/iwj.14575.
- Wu J, Sahoo JK, Li Y, Xu Q, Kaplan DL. Challenges in Delivering Therapeutic Peptides and Proteins: A Silk-Based Solution. Journal of Controlled Release. 2022;345:176-189. doi:10.1016/j.jconrel.2022.02.011.
- Hashemi S, Vosough P, Taghizadeh S, Savardashtaki A. Therapeutic peptide development revolutionized: Harnessing the power of Artificial Intelligence for Drug Discovery. Heliyon. 2024;10(22). doi:10.1016/j.heliyon.2024.e40265.
Further Reading