A peptide approach to regenerative medicine

Are regenerative peptides the answer to current challenges in developing treatments for unmet needs?

Regenerative medicine is a growing field with the potential to provide innovative new treatments for hard-to-treat diseases. Many treatments rely on the use of stem cells or cell therapies, but these are both technically difficult and expensive to produce. To address this problem, a number of biotechnology companies are looking for alternative ways to improve the effectiveness of regenerative medicine treatments, while improving their cost and accessibility.

Using new therapies, such as peptides, offers a different approach that can stimulate the body’s own cells to repair and regenerate at the site of damage, while avoiding the uncertainties of in vitro cell culture. The development of regenerative peptides offers an exciting opportunity to help patients with unmet needs in an affordable, accessible and predictable way.

Stem cell treatments face challenges

Stem cell therapies have been used in a wide range of biomedical applications, from treating burn victims with skin grafts to improving symptoms of osteoarthritis by injecting mesenchymal stem cells into affected joints. . However, to date, successes are rare and anecdotal. Results are often inconsistent, with great variability between patients, in part due to the delicate nature of stem cells. Even though the understanding of their characteristics and preferred culture conditions has improved over time, stem cells can still alter their surface markers and lose their capacity for self-renewal and differentiation during the process of cell growth and division, making treatments less effective.

The source of stem cells has also been the subject of ethical and political controversy. Today, induced pluripotent stem cells (adult cells that have been reprogrammed to regain the ability to differentiate) or hematopoietic stem cells (stem cells extracted and derived from umbilical cord blood) are the most common, but they are difficult to produce. Moreover, only specialized medical centers or facilities can meet the very specific conditions required for cell growth. This means that the cost of generating and maintaining sufficient stem cells for treatment tends to be high, reducing accessibility for patients.

Hope for platelet-rich plasma

In response to the challenges posed by stem cell research, many biotechnology companies are investigating other agents or treatments that can induce tissue regeneration to repair injuries and revitalize bodily functions. One approach is to use stimulating agents to activate the body’s own stem cells. For example, platelet-rich plasma (PRP) therapy is commonly used in orthopedic surgery and sports medicine, and more recently in the treatment of ocular surface diseases. PRP therapy uses injections of a concentration of a patient’s own platelets to speed up the healing process.

This treatment has several drawbacks, however, including unclear classification, due to different preparation methods, inconsistent naming conventions, and numerous reporting requirements. PRP has not yet been approved by the United States Food and Drug Administration, but is widely used in a variety of clinical settings.
In the case of applications in ophthalmology, most PRP studies have had positive results, with at least two-thirds of patients experiencing some improvement. It is, however, difficult to regulate the content of PRP treatments, as the level of relevant blood proteins may vary from patient to patient. For example, patients who have higher levels of signaling molecules, called inflammatory cytokines, in their blood may also have higher levels in their PRP, which can lead to negative effects and reduce the effectiveness of treatment.

Additionally, due to the way PRP treatments are absorbed and used by the body, most of the repair is superficial, as most of the proteins involved cannot reach the target site. This means that recovery of corneal sensitivity is limited. To further develop PRP as a standardized and stable treatment option, more studies are needed to better understand the importance of controlling for lot-to-lot differences in levels of key blood components, such as growth factors, platelets, leukocytes and cytokines. Alternatively, preparing treatments from pooled blood from multiple donors could help control and standardize the quality of PRP for more consistent results.

The power of regenerative peptides

Another approach to regenerative medicine uses new peptides to stimulate and regenerate patients’ own stem cells to speed up the healing process and repair damaged tissue. For example, pigment epithelium-derived factor (PEDF) is a multifunctional protein known to be both anti-inflammatory and anti-angiogenic, meaning it inhibits the growth of new blood vessels. Additionally, one of its functional domains is known to have stem cell regenerative properties and to support the growth, survival and differentiation of neurons and various stem cells. Numerous studies have shown that a fragment of this functional domain, called PEDF-derived short peptide (PDSP), can promote the growth and expansion of limbal epithelial stem cells, as well as meibomian gland stem cells. Therefore, it can be used to treat dry eye by accelerating the corneal repair process through stimulation of corneal stem cell proliferation and differentiation, anti-inflammation and meibomian gland recovery.

PDSP has also been shown to promote the growth of mesenchymal stem cells that can differentiate into multiple tissue types, including bone, cartilage, muscle, and fat cells and connective tissue. Therefore, it has the potential to treat other conditions, such as osteoarthritis, by promoting cartilage regeneration, repairing damage and relieving joint pain.

Regenerative peptides are attractive targets for drug development for several reasons. First, they are easy to manufacture, using a method called solid phase peptide synthesis (SPPS), which provides consistent quality and minimizes batch-to-batch differences. Every impurity is closely monitored and pre-specified during the manufacturing process to ensure drug quality.

Second, with an economy of scale, the cost of these drugs can be significantly reduced and may even be cheaper than PRP treatments. Third, with proper storage conditions and formulations, peptides can be manufactured in large quantities and stored for several years. This long shelf life greatly improves accessibility for patients, especially those living in rural areas.

Fourth, the use of a single natural peptide minimizes complications caused by immune responses, DNA toxicity, or inconsistencies in drug content, resulting in a better and more predictable safety profile. Finally, with consistent quality and scalable quantities, it is possible to conduct large-scale clinical trials to assess the effectiveness of regenerative peptide treatments on a wide range of patients and, therefore, to assess their potential for use in general populations.

Affordable, accessible and predictable treatments

PSDPs are already showing promising results. For example, the PDSP platform is being developed and optimized to address a range of diseases, such as dry eye syndrome, neurotrophic keratitis, limbal stem cell deficiency, wound healing skin and osteoarthritis.

In an ophthalmological application for the treatment of dry eye, the peptide has been tested in two phase II studies with over 300 patients and has shown an excellent safety profile and encouraging efficacy results. The drug is delivered through topical eye drops and the unique mechanism of action works by encouraging the regeneration of limbal stem cells. This method can achieve effectiveness much faster than traditional anti-inflammatory medications, which typically take around three to six months to achieve significant improvement. Patients can experience early benefits in terms of signs (an objective measure of the level of corneal repair) and symptoms (a subjective measure of patient feelings assessed by a questionnaire) within two weeks. Promising results from peptide studies demonstrate their potential as a more affordable, accessible and predictable approach to regenerative medicine.

As regenerative medicine technologies continue to advance rapidly, they are bringing hope to patients suffering from currently incurable diseases. While each approach has its own advantages and disadvantages, by working together as a research community and using each other’s strengths, we hope that many more creative solutions will soon bring transformative treatments to patients. References available upon request.