exploring new therapies targeting inflammatory skin diseases with novel, minimally invasive skin microbiopsy

Overview of a chronic inflammatory skin condition: Atopic Dermatitis 

Atopic Dermatitis (AD) is a chronic condition causing dry, itchy, and inflamed skin. It is common in young children but can occur at any age. It tends to flare periodically and is not contagious. AD is a common inflammatory skin disease affecting 13% of children and 7% of adults in the U.S. Childhood-onset AD often begins in the first year of life and can persists into adulthood in 20-50% of cases.^[1] 

Diagnosis can be straightforward in children but challenging in adults due to varied presentation. Diagnosis is traditionally based on clinical presentation and history, with exclusion of other conditions like seborrheic dermatitis, scabies, and psoriasis.^[2] 

Several tools are used to assess severity, including SCORing Atopic Dermatitis (SCORAD), Eczema Area and Severity Index (EASI), POEM, and Investigator Global Assessment (IGA). These tools consider factors like lesion extent, intensity, and patient-reported symptoms. Accurate severity assessment is crucial for selecting appropriate treatment and monitoring response. 

Dupilumab is today one of the most effective option for treating moderate-to-severe AD. Other systemic treatments include phototherapy, cyclosporine, methotrexate, and newer agents targeting specific pathways. New treatments targeting specific disease pathways, such as IL-13 and JAK inhibitors, are today in development. 

Indeed, traditional therapies often have limited effectiveness, making AD challenging to treat. The disease's heterogeneous nature complicates treatment, as individual responses to therapies can vary widely. 

The potential for a precision medicine approach to enable prevention and more effective long-term control of this complex disease 

Recent research has improved the understanding of the disease mechanisms, identifying new potential therapeutic targets. There is a growing emphasis on precision medicine approaches to tailor treatments to individual patients' needs.^[3] 

Over 70 new compounds are currently in development, targeting various aspects of the disease's pathophysiology. The potential for precision medicine to enable more effective long-term control and prevention of AD is crucial as AD has a significant impact on patients' quality of life and represents a considerable socio-economic burden. From Jay Bradner, M.D., executive vice president of Research and Development at Amgen, "many patients with moderate to severe atopic dermatitis struggle with chronic, life-disrupting symptoms”. 

There are numerous drugs currently in development for treating atopic dermatitis. These include a variety of monoclonal antibodies and small molecule therapies. Some notable examples are: 

• Monoclonal antibodies: Tralokinumab, GBR-830, Lebrikizumab, Tezepelumab, Fezakinumab, and Nemolizumab. 
• Small molecule therapies: Upadacitinib, Abrocitinib, Baricitinib, and Ruxolitinib. 
• Additionally, new drugs like SYX-5219, an oral pyruvate kinase M2 (PKM2) modulator, are in early-phase trials
  
  

Longitudinal monitoring of skin condition 

Plays a crucial role in the development of drugs for atopic dermatitis. Here are some key aspects: 

• Tracking Disease Progression: Longitudinal monitoring helps in understanding how the disease progresses over time, which is essential for evaluating the long-term efficacy and safety of new treatments^[4]. 
• Assessing Treatment Response: By regularly assessing the skin condition, researchers can determine how well a drug is working. This includes measuring improvements in symptoms like redness, itching, and skin barrier function^[5]. 
• Identifying Biomarkers: Continuous monitoring allows for the identification of biomarkers that can predict treatment response and disease severity. For example, biomarkers like interleukin (IL)-13 are used to monitor the clinical severity and response to treatments such as tralokinumab. 
• Personalizing Treatment: Longitudinal data can help tailor treatments to individual patients by identifying which therapies are most effective for specific patient subgroups. 
• Understanding Mechanisms: It provides insights into the underlying mechanisms of the disease and how different treatments affect these mechanisms over time^[6]. 

 Overall, longitudinal monitoring is vital for developing effective and personalized treatments for atopic dermatitis. 

The role of skin microsampling in drug development 

Minimally invasive skin sampling plays a significant role in the longitudinal monitoring of skin conditions like atopic dermatitis. Here are some key benefits: 

1. Reduced Patient Discomfort: Techniques like microdialysis and microneedle-based bioassays are less painful and less invasive compared to traditional biopsies^[7],^[8]. This makes it easier to perform frequent sampling without causing significant discomfort to patients. 
2. Frequent Monitoring: Because these methods are less invasive, they allow for more frequent sampling. This is crucial for tracking the progression of the disease and the effectiveness of treatments over time^[9]. 
3. Real-Time Data: Minimally invasive techniques can provide real-time data on various biomarkers, helping researchers and clinicians to make timely decisions about treatment adjustments. 
4. Lower Risk of Complications: These methods reduce the risk of complications such as infections and scarring, which are more common with traditional biopsy techniques. 
5. Improved Patient Compliance: The reduced discomfort and lower risk associated with minimally invasive methods can lead to better patient compliance, ensuring more consistent and reliable data collection. 

 Minimally invasive skin sampling enhances the ability to monitor skin conditions effectively and safely over long periods, which is essential for developing and optimizing treatments for diseases like atopic dermatitis. 

The Harpera™ Microbiopsy™ Punch is one of such minimally invasive skin microsampling device offering a virtually painless approach to collect skin samples. From Phase 1 trials to Phase 3 studies, the Harpera punch can allow Primary Investigators (PIs) to gather precise data while potentially improving patient retention and compliance. 

Just to cite one example in the field of AD drug development; The ability to analyze cytokine expression levels from lesional and non-lesional samples could provide insights into immune dysregulation, enabling personalized approaches to treatment.  

The Harpera punch 's efficiency also supports longitudinal studies, allowing researchers to monitor therapeutic outcomes over time. These features accelerate drug development and help investigators meet ethical standards for trial participants. 

Skin microsampling for ethical and practical pediatric applications 

Pediatric applications pose unique challenges in dermatology. Infants and children often experience heightened anxiety over medical procedures, making invasive biopsies particularly distressing. The physical and psychological impact of traditional biopsies—scarring, pain, and the use of anesthesia—further complicates sampling. 

The Harpera device could offer an ethical and practical alternative. Its minimally invasive design allows for painless sampling without scarring, even in cosmetically and sensitive areas like the face, neck, and diaper areas. By enabling repeated sampling over time, the use of Harpera punch could facilitate the monitoring of AD in pediatric populations, empowering clinicians to tailor treatments to the fluctuating nature of the disease; this represents a significant step forward in patient care and precise diagnostics in pediatrics. 

Future perspective - companion diagnostics and personalized medicine in Atopic Dermatitis 

Biological treatments for AD, such as FDA-approved Dupixent®, have revolutionized care for moderate to severe cases. However, the effectiveness of these treatments depends on understanding each patient's unique cytokine expression levels. Skin biopsies remain the gold standard for obtaining such data, but traditional methods are not suited for frequent or repeated use. 

Harpera could address this gap by enabling minimally invasive sampling that supports companion diagnostics. This technology allows clinicians to align treatments with individual patient profiles, optimizing outcomes. As more biological treatments enter the clinical pipeline, Harpera is poised to play a critical role in advancing personalized dermatology. 

Current barriers to Microbiopsy adoption and how to overcome them 

Despite its transformative potential, the Harpera device faces several adoption barriers: 

• Volume Sample Limitations: The small sample size restricts the range of biomarkers that can be analyzed. 
• Lack of Validated Workflows: Standardized protocols and historical usage data are needed to build trust and scalability. 

These challenges highlight the need for ongoing research, validation, and cost-reduction strategies to make the device more accessible and widely accepted. Harpera's benefits far outweigh its current limitations, particularly for clinical trials and dermatology research. 

• Ethical Compliance: The device aligns with low-risk ethical standards, reducing the need for invasive sampling. 
• Longitudinal Sampling: Researchers can collect data at multiple time points without compromising patient comfort or tissue integrity. 
• Remote Sampling: Its portable design facilitates decentralized research, expanding opportunities for clinical studies in remote or underserved areas. 

These features position Harpera as a vital tool for modern dermatological research, offering both precision and practicality. 

Future applications of Microbiopsy in dermatology research 

The potential applications of Harpera extend beyond AD. The device could play a pivotal role in pediatric studies of other dermatological conditions, such as psoriasis or eczema, where minimally invasive methods are essential. Additionally, as workflows and biomarkers are validated, Harpera could become integral to companion diagnostics and personalized medicine across dermatology, particularly in low-income settings where infectious and inflammatory skin diseases are prevalent. By addressing these challenges, Harpera could transform global dermatological care. 

Shaping the future of skin sampling with Harpera™ 

The Harpera™ Microbiopsy™ Punch exemplifies innovation in dermatological research, offering a minimally invasive, ethical, and precise alternative to traditional biopsies. Its ability to support longitudinal studies, enhance patient compliance, and align with personalized medicine makes it a cornerstone for advancing dermatology. As researchers and clinicians continue to explore its applications, the Harpera device has the potential to redefine skin sampling standards, ensuring better patient outcomes and groundbreaking discoveries in dermatological science.