Scientists create next-generation hair loss treatment safe for both men and women

A little change in the cycle that produces hair could tip the scales toward either healthy, continued hair growth or slow, progressive hair reduction. Many individuals suffering from hair loss have hair follicles that become “stuck” in their resting phase without moving into growth mode.

A research team set out to determine how to unlock that “stuck” phase.

A combined team from Kyungpook National University and the Daegu Gyeongbuk Institute of Science and Technology created a synthetic peptide that appears to trigger the hair follicle to resume growth. Unlike other products currently in use, it does not exhibit the same unwanted side effects experienced by users of those products.

This investigatory team’s candidate, the peptide known as MLPH, was developed using a fragment of erythropoietin (EPO), a natural hormone known to control the production of red blood cells.

The team’s goal is to address consumers’ concerns about the negative side effects associated with current treatments for hair loss.

Approximately 1 billion people worldwide are affected by hair loss. The marketplace for treatment is dominated by two medications, minoxidil and finasteride. While effective, these medications have their benefits and drawbacks.

Minoxidil can cause irritation of the scalp. Finasteride alters hormonal pathways and may be inappropriate for use in many women. Both products do not directly impact the cellular processes that control hair cycling.

Research has long established that, under specific conditions, EPO stimulates growth of hair follicles via attachment to hair follicle receptors. However, when applied systemically, EPO raises levels of red blood cells, resulting in potential complications.

The team’s strategy seeks to separate these two effects.

In their own words, “We have eliminated the parts of EPO that result in unwanted side effects, and have isolated the active component that stimulates hair follicle growth.”

To identify a small region of EPO that binds to follicle cells, scientists created a 3D model using computer simulations rather than using the entire hormone. After developing multiple peptide versions of EPO based on this information, they determined which ones would best show affinity to the EPO receptor.

MLPH emerged as the best candidate.

In their structural modeling, the researchers visualized that MLPH was likely to form stable interactions with the EPO receptor. They also found that MLPH displayed a strong propensity to form the helical structure necessary for activating the receptor. This structure helps elicit a biological response from the downstream signaling cascade associated with the receptor.

To investigate the potential function of MLPH as an agonist to stimulate hair growth, the researchers treated both human hair follicle samples and murine (mouse) samples with MLPH.

Hair follicles go through three distinct cycles: growth (anagen), involution or regression (catagen), and dormancy or resting phase (telogen). The inability of the follicle to enter the growth phase is indicative of hair shedding.

MLPH has shown the ability to reverse this process.

In mouse model studies, the treated hair follicles moved from the dormant (telogen) phase into active growth (anagen). Microscopic examination of skin tissue showed evidence of anagen, including deeper follicles, increased thickness of the hair follicles, and an increased rate of cell division.

In cultured human hair follicles, the hair shafts produced by treated samples were, on average, longer than the untreated control over a period of six days. This result was similar to outcomes previously observed with minoxidil exposure.

Insulin-like growth factor 1 (IGF-1) was the most abundant signaling molecule produced by cells cultured in the presence of MLPH. Levels rose to up to three times greater than baseline after only a few days of exposure. This indicates that MLPH promotes the release of IGF-1 from follicular cells.

The peptide IGF-1 is pivotal in maintaining the growth status of hair follicles, as it promotes cellular survival and the creation of new hair fibers.

The fact that blocking IGF-1 signaling diminished the effect of the peptide on hair fiber growth suggests that the peptide produces a direct effect on follicle development through specific pathways. This occurs rather than through an indirect effect via several different pathways.

A benefit of this peptide over EPO is that it did not produce the same effects on red blood cells in preclinical studies.

For example, mice treated with MLPH had no difference in red blood cell counts, total hemoglobin, or hematocrit values compared to placebo-treated animals. However, animals treated with EPO showed significantly increased levels in these parameters.

This difference is largely due to the design of MLPH. Removing the components of the EPO molecule responsible for stimulating red blood cell production leaves a product that retains only its regenerative signaling properties.

Professor Cheil Moon at DGIST stated, “The MLPH peptide developed in this study represents a novel, safe, mechanism-based treatment option that will provide therapeutic benefit to patients, without the gender or blood-related side effects associated with currently available products.”

The peptide acts specifically on dermal papilla cells, which serve as the cellular control center for the hair follicle. These cells determine when the follicle grows or rests.

In many cases of hair loss, dermal papilla cells have reduced activity.

This study found that MLPH increased both the proliferation and metabolic activity of dermal papilla cells. It also reduced the effects of oxidative stress, which can compromise the function of hair follicles.

MLPH activates two signaling pathways in dermal papilla cells, namely the AKT and ERK pathways. Both pathways are associated with cellular survival and growth. Their activation leads to increased IGF-1 production in these cells, supporting hair regeneration and growth.

The results indicate a more concentrated means of controlling hair follicle development, focused on the cellular mechanisms of the follicle rather than broader physiological systems.

The findings, however, are in their infancy. Research has primarily been conducted using cultured human tissue and preclinical mouse models.

Future studies will focus on long-term safety, methods of delivery, and effects on various forms of hair loss. It will also be important to investigate how MLPH behaves with repeated use and under real-world conditions, and whether it effectively reaches the dermal papilla of hair follicles.

On a practical level, if these findings are replicated in subsequent studies, the MLPH peptide or similar peptides could represent a new therapeutic class. These treatments would target cellular mechanisms associated with hair loss without hormonally induced side effects.

This could expand treatment options for both men and women who are not able to use current medications. It may also influence the design of future therapies by focusing on specific intracellular signaling in the hair follicle instead of indirect stimulation of these mechanisms.

Research findings are available online in the journal Biomedicine & Pharmacotherapy.

The original story "Scientists create next-generation hair loss treatment safe for both men and women" is published in The Brighter Side of News.

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