Our mission is to develop innovative, non-pharmacological medical devices for the management of inflammatory skin diseases and conditions, offering a safe and effective alternative to steroid-based therapies.
Leveraging our proprietary HA c-40 technology, we target the skin microbiota and its interkingdom interactions to restore skin homeostasis and support long-term disease management across pediatric and adult populations (Magnifico et al., 2020; Paller et al., 2019). Through a science-driven approach, we aim to address unmet needs in dermatology while improving patient quality of life.
Mechanism of Action
HAc40 is a proprietary macromolecular conjugate developed through an innovative patented process that chemically links a purified fragment of the beneficial bacterial cell wall derived from Cutibacterium acnes DSM 28251 to sodium hyaluronate or other mucopolysaccharides.
HA c-40 Technology
HAc40 is designed as a microbioma-modulating system targeting the pathological dysbiosis associated with inflammatory skin conditions such as atopic dermatitis and psoriasis. Its activity is based on a dual mechanism of action:
1. Skin barrier protection
Experimental evidence indicates that HA c-40 interferes with the pathogenic activity of Staphylococcus aureus-derived extracellular vesicles (EVs) on keratinocytes. In vitro studies show that treatment with HAc40 leads to:
- Modulation of EV biophysical properties: including an increase in vesicle size, reducing cellular interaction and penetration into the deeper epidermal layers (Pietrangelo et al., 2021; Pietrangelo et al., 2023)
- Reduction of EV-induced keratinocytes cytotoxicity: protecting the viability of the skin’s primary cellular defense.
- Preservation of tight junction (TJ) proteins: including zona occludens-1 (ZO-1) and claudin-1 (CLDN1), thereby supporting the maintenance of epidermal barrier integrity and preventing barrier disruption (Magnifico et al., 2023; Petronio Petronio et al., 2024)
2. Microbiota modulation
In parallel, HAc40 has been shown to modulate the cutaneous microbiota by preserving commensal microbial populations, thereby supporting the maintenance of a balanced and resilient cutaneous ecosystem (Nakatsuji et al., 2017).
This dual mechanism—combining barrier protection and microbiota modulation—positions HAc40 within a novel therapeutic paradigm focused on restoring skin homeostasis, rather than solely targeting inflammatory pathways.
These effects translate into an improved barrier function, including a reduction in transepidermal water loss (TEWL) and a consequent improvement in skin hydration (Monola et al., 2023).
Safety and Platform Advantages
The use of non-viable bacterial components provides an improved safety profile, as HAc40 contains no live or inactivated microorganisms. This eliminates any risk of microbial replication and horizontal gene transfer events, including the potential dissemination or selection pressure associated with antibiotic resistance mechanisms.
References
1. Magnifico, Irene et al. “A Wall Fragment of Cutibacterium acnes Preserves Junctional Integrity Altered by Staphylococcus aureus in an Ex Vivo Porcine Skin Model.” Pharmaceutics vol. 15,4 1224. 12 Apr. 2023, doi:10.3390/pharmaceutics15041224
2. Magnifico, Irene et al. “Atopic Dermatitis as a Multifactorial Skin Disorder. Can the Analysis of Pathophysiological Targets Represent the Winning Therapeutic Strategy?.” Pharmaceuticals (Basel, Switzerland) vol. 13,11 411. 22 Nov. 2020, doi:10.3390/ph13110411
3. Monola, A., et al. (2023). Evaluation of a HA-conjugate system in restoring the skin barrier and modulating the microbiome in atopic-prone skin. Dermatological Reports (In Press/Selected Proceedings).
4. Nakatsuji, T., et al. (2017). Antimicrobials from human skin commensal bacteria protect against Staphylococcus aureus and are deficient in atopic dermatitis. Science Translational Medicine, 9(378), eaah4680.
5. Paller, A. S., et al. (2019). The microbiome in patients with atopic dermatitis. Journal of Allergy and Clinical Immunology, 143(1), 26-35.
6. Petronio Petronio, Giulio et al. “Targeting S. aureus Extracellular Vesicles: A New Putative Strategy to Counteract Their Pathogenic Potential.” Pharmaceutics vol. 16,6 789. 11 Jun. 2024, doi:10.3390/pharmaceutics16060789
7. Pietrangelo, Laura et al. “Efficacy and Microbiota Modulation Induced by LimpiAL 2.5%, a New Medical Device for the Inverse Psoriasis Treatment.” International journal of molecular sciences vol. 24,7 6339. 28 Mar. 2023, doi:10.3390/ijms24076339
8. Pietrangelo, Laura et al. “LimpiAD foam and the potential control of the pressure ulcers onset.” Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie vol. 144 (2021): 112327. doi:10.1016/j.biopha.2021.112327
References
1. Magnifico, Irene et al. “A Wall Fragment of Cutibacterium acnes Preserves Junctional Integrity Altered by Staphylococcus aureus in an Ex Vivo Porcine Skin Model.” Pharmaceutics vol. 15,4 1224. 12 Apr. 2023, doi:10.3390/pharmaceutics15041224
2. Magnifico, Irene et al. “Atopic Dermatitis as a Multifactorial Skin Disorder. Can the Analysis of Pathophysiological Targets Represent the Winning Therapeutic Strategy?.” Pharmaceuticals (Basel, Switzerland) vol. 13,11 411. 22 Nov. 2020, doi:10.3390/ph13110411
3. Monola, A., et al. (2023). Evaluation of a HA-conjugate system in restoring the skin barrier and modulating the microbiome in atopic-prone skin. Dermatological Reports (In Press/Selected Proceedings).
4. Nakatsuji, T., et al. (2017). Antimicrobials from human skin commensal bacteria protect against Staphylococcus aureus and are deficient in atopic dermatitis. Science Translational Medicine, 9(378), eaah4680.
5. Paller, A. S., et al. (2019). The microbiome in patients with atopic dermatitis. Journal of Allergy and Clinical Immunology, 143(1), 26-35.
6. Petronio Petronio, Giulio et al. “Targeting S. aureus Extracellular Vesicles: A New Putative Strategy to Counteract Their Pathogenic Potential.” Pharmaceutics vol. 16,6 789. 11 Jun. 2024, doi:10.3390/pharmaceutics16060789
7. Pietrangelo, Laura et al. “Efficacy and Microbiota Modulation Induced by LimpiAL 2.5%, a New Medical Device for the Inverse Psoriasis Treatment.” International journal of molecular sciences vol. 24,7 6339. 28 Mar. 2023, doi:10.3390/ijms24076339
8. Pietrangelo, Laura et al. “LimpiAD foam and the potential control of the pressure ulcers onset.” Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie vol. 144 (2021): 112327. doi:10.1016/j.biopha.2021.112327