A Non-Invasive Biomarker Platform Using Plucked Hair for Effective Analysis

Easily accessible good quality tissue is crucial for successful biomarker assays. The use of the plucked hair follicle as a surrogate tissue has gained increased attention in recent years. This Epistem innovative biomarker platform is non-invasive and robust, revolutionizing pharmacodynamic monitoring, and patient stratification.

In this article, we examine the use of scalp hair as a surrogate tissue for biomarker analysis and explore how it is becoming an increasingly useful tool within medical research.

p-ERK labelling in the outer root sheath (ORS) of a hair follicle section. The heat-map overlay displays the labelling. This algorithm measures the percentage of ORS area that is positively labelled, divided into three labelling intensity thresholds: Strongly labelled (red), moderately labelled (orange) and weakly labelled (yellow). Blue areas are negative or where labelling is below the minimum intensity threshold. Each of these regions may be individually quantified.

A Decade of Scalp Hair Biomarker Expertise

For over a decade, Epistem has been at the forefront of unlocking the research potential of scalp hair as a biomarker tissue. Hair follicles are highly vascularised, which allows efficient exposure to therapeutic agents. This unique combination of vascularity in an epithelial tissue that is rapid proliferating makes the hair bulb and outer root sheath cells ideal surrogate biomarker tissues for solid tissue drug responses.

The Power of Proof-of-Concept Studies

One of the compelling aspects of using hair as a biomarker tissue is the ease with which proof of concept studies can be conducted. In these studies, plucked scalp hairs from healthy volunteers are exposed to a drug of interest for a specified period. Following exposure changes in gene or protein expression are evaluated. Researchers can measure direct changes to the target, such as phosphorylation, through immunohistochemistry (IHC), or examine alterations induced in downstream gene pathways to generate a unique response signature.

This hair biomarker platform offers invaluable insights for drug development programs, aiding in:

• Monitoring pharmacodynamic responses to treatment.
• Confirming the mechanism of action.
• Stratifying patients based on their biomarker profiles.

Hair Immunohistochemistry: Precision in Protein Analysis

Epistem has also advanced the field of IHC for plucked human scalp hairs. These techniques allow for reliable and reproducible labelling of proteins and site-specific phosphorylation within individual hair samples. Individually optimised protocols allow for customized labelling and quantification options for each antigen of interest.

Formalin-fixed paraffin-embedded (FFPE) longitudinal sections of hair follicles are prepared and subjected to IHC, which can be performed manually or via automated processes. The quantification of specific labelling within each follicle is then achieved via scanned images using the Aperio® ScanScope®, where parameters such as the number of labelled cells, variations in labelling intensity or spatial distribution can be precisely quantified.

Hair Gene Expression: Unlocking Comprehensive Analysis

Gene expression profiling in hair samples is helpful in situations where the target or pathway is unknown. It is also useful when suitable antibodies for protein analysis are not available. This approach enables the simultaneous measurement of multiple gene changes with minimal intra- and inter-donor variation. Epistem’s extensive database, which contains gene expression profiling information from mouse, rat, and human samples, plays a crucial role in confirming the expression of genes of interest in hair.

By exposing hair to a drug ex vivo, researchers can establish drug-related changes in gene expression and potentially generate a unique gene signature. This comprehensive analysis unlocks new possibilities in understanding drug responses and their impact on biological pathways.

The Ideal Surrogate Tissue vs. Blood & Skin Tissue

Why is hair the ideal surrogate tissue for monitoring drug responses? Several key factors provide an advantage over other regularly used tissues such as skin or blood:

Ease of Sampling: Hair is easily accessible and can be plucked with minimal discomfort to the patient whilst leaving no unwelcome cosmetic marking. This simplicity in sampling is a significant advantage over other tissues where sampling may be far more invasive.

Patient Compliance: Patients are generally more willing to provide hair samples compared to more invasive methods thus ensuring a higher rate of compliance in clinical studies.

Ethical Considerations: Hair sampling raises fewer ethical concerns than other tissue sampling methods which makes it a more attractive option for both researchers and patients.

Multiple Independent Samples: Plucking several hair follicles yields multiple independent samples at each time point, enhancing the reproducibility and robustness of subsequent biomarker analysis.

Concluding Remarks

In conclusion, the use of plucked hair as a biomarker tissue has emerged as a critical tool in drug development. Epistem’s pioneering work in this field has showcased the versatility and effectiveness of hair as a surrogate tissue, offering researchers a powerful alternative surrogate tissue for monitoring drug responses, understanding mechanisms of action, and tailoring treatments to individual patients. As the world of biomarker analysis continues to evolve, the perfect surrogate may just be a few strands of hair away.

What Epistem Can Offer

Epistem offers a full suite of services, including sampling kits for clinical studies with detailed collection guides for accurate and high-quality sample collection. We also provide additional remote training to further ensure standardised plucking and subsequent sample preservation.  All our hair biomarker studies adhere to GCLP standards.

With a proven track record of supporting major pharmaceutical customers in their drug development pipelines using plucked hairs as a surrogate biomarker, Epistem stands as a trusted partner in advancing the future of pharmacodynamic monitoring and patient stratification.