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Joining us is Dr. Jasmina Jankicevic, the Chief Medical Officer of Innovaderm. Dr. Jankicevic is a globally recognized authority in the field of dermatology drug and medical device development. Her extensive experience encompasses all phases of clinical research leading to many regulatory approvals. She has contributed significantly to the scientific community with her numerous talks and publications. Her expertise is not limited to dermatology but also extends to immunology and aesthetic medicine.
We will dive into gene therapy, exploring 3 crucial points in our discussion:
- Gene Therapy: The Potential Future of Dermatology
- Stem Cell Therapy: Its Influence on Dermatology Treatment
- Key challenges to Consider in Gene Therapy Investigations
The Potential Future of Gene Therapy in Dermatology
Gene therapy in dermatology has been originally focused on a few genetic disorders. The most significant progress has been made in the case of hereditary dystrophic epidermolysis bullosa, where the first gene therapy for both dominant and recessive forms has been approved. Other potential candidates in terms of genodermatoses that conceptually could be managed by gene therapy are diseases such as epidermolysis bullosa simplex, junctional epidermolysis bullosa, pachyonychia congenita, Netherton syndrome, xeroderma pigmentosum, lamellar ichthyosis, X-linked ichthyosis, Harlequin ichthyosis, and even nebulous congenital ichthyosisform erythroderma.
In essence, whether through ex vivo, in vivo, or gene editing approaches, we have a vast area to explore and validate for safety and effectiveness. Equally, if not more crucial, is ensuring manufacturing and commercial sustainability.
Gene therapy research is not confined to genodermatoses. It also plays a role in wound healing, cancer treatments like melanoma and squamous cell carcinoma, immunomodulation, and potentially in combating skin aging as part of the regenerative medicine movement. For instance, in wound healing, gene transfer is simpler due to the absence of an epidermal barrier. The treatment area is limited, and therapy is only needed until the wound fully heals.
Research into refractory burn wounds, diabetic ulcers, vascular ulcers, and decubital ulcers holds great promise for expedited healing. Additionally, it is hoped that the newly regenerated skin would be less prone to irregular healing and potential scarring, particularly in the development of hypertrophic and keloid scars.
Stem Cell Therapy
Stem cells are fascinating. They are essentially undifferentiated cells found in various organ systems, possessing 2 defining characteristics. The first is self-renewal, signifying their capacity to go through numerous cycles of asymmetrical cell division to generate either differentiated cells or cells closely resembling the parent cell.
The second trait is differentiation, which is the stem cell’s capacity to evolve into cells of the tissue where it resides. Interestingly, they also possess what is known as plasticity or transdifferentiation. This is the ability of an adult stem cell to differentiate into cells of a tissue different from its original tissue.
In the context of the skin, stem cells from the epidermis, hair follicles, and sebaceous glands undergo multiplication and differentiation independently, unless a problem arises. For instance, in the event of an injury, a stem cell from any of these locations has the potential to produce an entire cell lineage.
Dermatological conditions such as systemic sclerosis, systemic lupus erythematosus, pemphigus, psoriasis, and vitiligo have attracted attention in both preclinical and clinical settings. Wound healing, which presents multiple approaches, along with scleromyxedema, hair loss, melanoma, and aesthetic medicine, also fall under the areas of focus.
Therapies based on stem cells hold potential for addressing both degenerative and inflammatory diseases. However, these therapies necessitate careful consideration. The propensity of stem cells for self-renewal and differentiation is significantly influenced by their local environment, complicating predictions of their behavior within the human body. Factors such as changes in oxygen levels within the stem cell niche can affect their rate of proliferation, pluripotency, and ultimately, phenotype. Therefore, the isolation and characterization of stem cells become critical, even though the survival rates of isolated stem cells may be low.
Moreover, the cultivation of stem cells without contamination demands highly sophisticated laboratory procedures. Adding to the complexity is the need for careful monitoring, a fundamental aspect of stem cell therapy, given that stem cells can lose genetic stability over time and become more prone to malformation.
Furthermore, therapies based on stem cells necessitate regular follow-ups to monitor the regenerated tissue throughout the patient’s recovery period. The efficiency and timeliness of cell processing and manufacturing are areas that need improvement. Future research focusing on optimal patient selection, intervention timing, suitable conditioning regimens, post-intervention care, and cost-effectiveness could enhance the outcomes of stem cell therapy.
Key Challenges to Consider in Gene Therapy Investigations
The complexities of gene therapy and clinical research primarily stem from decision-making processes and informed consent. Misunderstandings about the nature of the intervention and associated risks can arise, particularly when participants are dealing with debilitating or life-threatening diseases. This can lead to an overestimation of benefits and an underestimation of potential safety issues. Therefore, it is crucial to provide patients with comprehensive information to prevent unrealistic expectations or misconceptions about safety.
Another consideration is the irreversible nature of gene therapy, which means that the right to withdraw consent does not apply in the same way as it does for continued medical treatments. The probabilities and outcomes of adverse events related to gene transfers are challenging to define and completely predict. Gene therapy brings up concerns about long-term safety and efficacy, as well as serious or irreversible side effects.
The main risks include technical issues related to the quality and stability of transgene expression, the transfer of an unwanted gene, the administration of a replication-competent virus, or bacterial contamination of vector preparation. Other potential issues include immune responses and unintentional modification of germinal cells, among others.
Both viral and non-viral vectors still present challenges in terms of efficacy and safety. From a regulatory perspective, gene therapy is likely to remain strictly regulated, potentially leading to increased bureaucracy and costs, and decreased speed and adoption in clinical trials. However, due to the relative ease of gene transfer, dermatological disorders could become prime targets for gene therapy.
To make this a reality, significant investments will be required, along with close collaboration with regulatory agencies to gain approval for intelligent clinical development programs. These programs should address current safety concerns and efficacy shortcomings, keeping the market access environment in mind from the beginning. This approach will ensure that all patients who need these therapies can access them once approved.
As we conclude another illuminating episode of Phase Forward, we find ourselves at the crossroads of science and progress. Remember that behind the jargon and statistics, lies stories of unwavering commitment, meticulous observation, and the pursuit of evidence that shapes our understanding of health and disease. Stay at the forefront of knowledge and innovation and follow Phase Forward on your preferred platform. My name is Valerie Coveney. Thank you for joining us. Until next time.
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