Day 2 :
Keynote Forum
Aziz Ghahary
University of British Columbia, Canada
Keynote: A new approach in preventing hypertrophic scarring/keloid
Time : 10:00-10:45
Biography:
Aziz Ghahary, PhD and Professor, is the Director of the BC Professional Firefighters ‘Burn and Wound Healing Research Group and has published more than 168 peer-reviewed articles some of which directly related to autoimmune diseases such as type I diabetes. He has been awarded more than 50 research grants from different local, national and international granting agencies. He is the leading investigator in identifying a serum 14-3-3 eta protein as a biomarker for early detection of RA and psoriatic RA and this test has now been launched by the Quest Diagnosis and Lifelab in US and Canada, respectively. Finally, he recently identified a small molecular with anti-scaring properties, which has now been approved by the Health Canada and the Vancouver General Hospital Ethic Committee to proceed to Phase 1 Clinical Trial.
Abstract:
Wound healing outcome is regulated by a fine balance between deposition and degradation of extracellular matrix (ECM). Over healing formation such as keloid is mediated by exaggerated ECM deposition and abnormalities in ECM degradation. Current treatment modalities for prevention of keloid and hypertrophic scarring have limited efficacy, which raised a great need for innovation within wound care industry. Moving toward novel approaches to prevent these devastating conditions, we identified the anti-scarring properties of Kynurenic acid (KynA), a naturally occurring small molecule generated from tryptophan degradation. To slow down/prevent keloid and hypertrophic scar formation, we have delivered KynA within the wounds before and/or during epithelialization by using either topical application of KynA containing cream or KynA slow releasing dressing. The results showed a significant outcome improvement in a fibrotic rabbit ear model received this therapeutic agent. During the course of this talk, the challenges associated with dermal fibrosis will be presented, the reason for choosing KynA as a potent anti fibrogenic factor will be discussed, in vitro data on efficacy of KynA as an ECM modulating factor in favor of improving the wound healing outcome will be presented, the benefit of using KynA in a topical cream and slow releasing dressing on a fibrotic rabbit ear model will be shown, finally the safety result of KynA cream in a phase 1 clinical trial will be presented. At the end, the conclusion and the future direction of using KynA as a potent anti-fibrogenic factor for treatment of keloid and hypertrophic scarring will be presented.
- Skin and Infectious Diseases | Dermatologic Surgery | Therapies for Skin Disorders | Genodermatosis | Diagnostic and Clinical Analysis | Dermatological Diseases
Location: Fraser North
Chair
Pieter Spee,
FibroTx LLC, Estonia
Co-Chair
Devashri Mukherjee
Decision Resources Group, India
Session Introduction
Pieter Spee
Chief Technology Officer FIBROTX Innovations for skin Europe
Title: Towards skin point-of care devices for personalized skin treatment based on non-invasive biomarker measurements directly from the skin surface
Biography:
Pieter Spee has received his PhD in immunology from the Netheralands Cancer Institute/University of Leiden (NL). While at Novo Nordisk, he made significant contributions to Lirilumab and Monalizumab, both currently in phase II clinical development by BMS and AstraZeneca in collaboration with Innate Pharma, respectively. As a Director and Scientific Director he was heading up preclinical translational research at Novo Nordisk. In 2012, he founded PS! Pharmaconsult, offering expert advise on drug and medical device development through a unique 360 degrees patient centric approach. Currently, he functions as chief technology officer at FibroTx LLC, developing two highly innovative skin diagnostic devices, TAP and SELF, allowing personalized medicine in skin care and clinical dermatology.
Abstract:
Diagnosis of chronic skin inflammation is largely performed by visual assessment, for instance by judging the shape, pattern, position, thickness, redness and scaling of skin lesions on the body. These phenotypic characteristics are typically end-products of the underlying biological processes responsible for disease. Despite the unquestionable value of visual assessment for treatment decisions and patient monitoring, more detailed analyses methods are needed for answering the unmet medical need for offering personalized medicine to patients, e.g., methods that can be used for selection as well as fine-tuning of treatment. Proteins that play a crucial role in skin inflammation, such as cytokines and chemokines, form the molecular root of inflammation and thus have tremendous value for catering personalized medicine in the form of biomarkers. Skin biomarker measurements are typically performed on skin material obtained through invasive procedures and analyses are typically costly and elaborate. FibroTx TAP and SELF are novel molecular diagnostic platform technologies for biomarker measurements directly from skin. These platform technologies are currently being tested in clinical studies for the development of skin diagnostic tools that can objectively assess the disease activity status of skin lesions. The aim of the studies is to develop practical point-of-care devices that can markedly improve skin treatment, which is cost-efficient and does not require the need for extensive clinical laboratory expertise.
Colin P White
Surrey Memorial Hospital, Canada
Title: Local skin flap utilization for cutaneous malignancies: A practical approach for success to reconstruction
Biography:
Colin P White is a Plastic Surgeon in British Columbia, Canada. His clinical practice includes skin cancer surgery, hand surgery and congenital & trauma reconstruction.
Abstract:
The approach to superficial melanoma and non-melanoma skin cancer reconstruction is complex. Surgical excision and reconstruction can be approached in multiple ways depending on the size of defect, tissue quality, tissue character and position of hairline. The most important factor in skin cancer reconstruction is the location of the defect relative to the anatomic body area. An effective solution to skin defects is not always advanced complicated skin flaps but primary closure and skin grafts can work quite well when used appropriately. We will show that knowledge of basic reconstruction of areas such as the nose, ear and lower extremity are best done with a combination of complex local flaps like the bilobed flap, keystone flap and basic skin grafts. We will show successes and failures of different techniques at sites. The keystone flap is emphasized, as this flap tends to be underutilized and can be of tremendous help in areas such as the lower extremity. We also show that where appropriate primary closure and skin grafts which are often perceived as easier reconstructions can have far superior cosmetic results than more complex flaps. We would like to encourage use of this approach for complex defects and other defect closures. There are several basic principles that we believe are key when approaching various skin defects and we would like to highlight these components during our talk.
Layla Nabai
Dermatologist pursuing PhD in Wound Healing
Title: Controlled delivery of kynurenic acid: A novel approach to prevention of post-surgical fibrosis
Biography:
Layla Nabai is a Dermatologist pursuing PhD in Wound Healing. Her focus is hypertrophic scarring with emphasis on its prevention. Her novel approach involves the use of controlled release drug delivery system which has gained a lot of interest in recent decades. She has worked on controlled delivery of the small molecules with anti-fibrogenic property to the wound bed.
Abstract:
Statement of the Problem: Hypertrophic scars and keloids are devastating fibrotic conditions. Despite advances in knowledge and various therapeutic methods prevention and treatment of these conditions remains a challenge. Our group has previously shown that kynurenic acid (KyA) as a topical formulation reduces hypertrophic scarring in rabbit ear model. In this study we hypothesized that the use of a biocompatible and biodegradable polymer microsphere for controlled slow release of KyA will reduce fibrosis in closed wound in a rat model.
Methods: The FDA approved Poly (lactic-co-glycolic acid) (PLGA) polymer was used to encapsulate KyA. An animal model of wound healing which involves subcutaneous implantation of pre-cut PVA sponges in rat was used to evaluate the in vivo efficacy of the microspheres.
Results: The in vitro experiments revealed a successful encapsulation of KyA (average encapsulation efficiency=80.65±18.49%) and a release profile that showed a gradual release over 35 days following a lag phase for 30 days. Both histological examination and hydroxyproline assay of the samples harvested after 66 days revealed a significant reduction in collagen deposition inside and around the PVA sponge implants loaded with KyA microspheres compared with the PVA alone or loaded with empty microspheres (0.3±0.5, 6.74±2.77, 2.7±0.89 mg collagen/PVA respectively). There was no significant difference between samples collected after 35 days.
Conclusion & Significance: Our data suggests that gradual release of KyA after 30 days can prevent fibrosis in vivo while the lag phase allows normal healing process to occur. This drug delivery system provides a novel approach toward prevention of fibrosis after surgical interventions.
Pooya Khan Mohammad Beigi
University of British Columbia, Canada
Title: Efficacy of “Interferon alpha-2a combined with PUVA†compared with “PUVA monotherapy†in various stages of Mycosis Fungoides (MF)
Biography:
Pooya Khan Mohammad Beigi is a Clinical Research Fellow at the Child & Family Research Institute affiliated with the University of British Columbia, Canada and the President/Owner of the NWM Medical Clinic, Canada. He is also the Founder/CEO of Misdiagnosis Association and Society, USA and Founder/CEO of Father Medical Charity, Canada. He is the author of several books in the medical field including Acrodermatitis Enteropathica: A Clinician's Guide (2015), A Clinician's Guide to Mycosis Fungoides (2016), A Clinician's Guide to Pemphigus Vulgaris (2016), A Clinician's Guide to Psoriasis (2017) and A Clinician's Guide to Alopecia Areata (2017).
Abstract:
Mycosis fungoides (MF) is the most common form of cutaneous T-cell lymphoma (CTCL). Even though phototherapy is one of the most effective treatment methods during the early phases of MF, it does not seem to be as effective for long-term remission when used solely. The use of interferon as an effective immunotherapy in the treatment of MF could be considered as an adjunctive therapy. The objective of this study was to compare the efficacy of the two treatment methods, PUVA monotherapy and PUVA combined with interferon alpha-2a. This study examined 150 patients diagnosed with MF through biopsy, who were either treated with PUVA or PUVA and interfron 2A at Razi Dermatology Hospital during the years of September 2005 to August 2015. In PUVA monotherapy group, all patients at stage IA had complete or partial remission. However, patients at stages III or IVA did not respond to treatment. In PUVA+INF group, all patients at stage IA had complete or partial remission but similar to PUVA alone group, patients in stages III or IVA did not respond to treatment. Complete remission was found in 78.6% of patients at stage IA, 57.1% of stage IB and 75% of stage IIA. Partial remission was documented in 21.4% of patients at stage IA, 28.6% of stage IB and 25% of stage IIA. 66.7% of patients at stage III and 75% of individuals at stage IVA did not respond to treatment (P=0.007). Complete and overall remissions showed no significant difference based on the type of treatment. This study found that PUVA alone and the combination of PUVA with interferon are both effective in patients with MF, especially at the early stages of MF.
- Skin and Infectious Diseases | Dermatologic Surgery | Therapies for Skin Disorders | Genodermatosis | Diagnostic and Clinical Analysis | Dermatological Diseases
Location: Fraser North
Chair
Madalene C Y Heng
David Geffen School of Medicine at UCLA, USA
Co-Chair
Pieter Spee
FibroTx LLC, Estonia
Session Introduction
R B Jalili
University of British Columbia, Vancouver, BC, Canada
Title: Application of Adipose Derived Progenitor Cells for Treatment of Chronic Wounds
Biography:
Dr. Jalili is an Assistant Professor in the Department of Surgery at the University of British Columbia. He is a Principal Investigator at ICORD. Dr. Jalili attended the Tehran University of Medical Sciences for his M.D. and the University of British Columbia for his Ph.D. in Experimental Medicine.
Abstract:
Introduction: Chronic wounds such as diabetic foot ulcers usually fail to progress through the normal wound healing process. Despite widespread effort, current conventional prevention and treatment methods have neither decreased prevalence of these ulcers nor significantly improved their outcomes. This speaks to the need for development of innovative and clinically translatable strategies for treatment of chronic wounds. Stem cell therapy has been examined as a therapeutic approach to chronic wounds throughout the past decade. The use of Adipose derived cells (ADCs) in treatment of chronic wounds has been both promising and practical treatment because of its relatively non-invasive extraction, high proliferation rate, and ability to differentiate into several mesodermal lineages. It has been shown that wounds treated with ADCs applied in the combination of a three-dimensional scaffold exhibit the greatest wound healing outcome.
Methods: In this study, we developed a novel bio-hybrid system comprising an injectable biocompatible crosslinked matrix that is populated with adipose derived cells to form a scaffold within the wound bed. Layers of a nano-woven biopolymer mesh were then served to enhance graft toughness and restore tissue homeostasis ultimately improving the rate of healing of a chronic wound. We compared the viability of adipose derived cells in vitro in combination with and without this bioengineered in-situ forming skin substitute and then applied it in treatment of full-thickness wounds in a pilot murine chronic wound model.
Results: Adipose derived cells (ADCs) exhibited greater viability and functional characteristics when cultured with the bioengineered skin substitute than those cultured alone. Gross wound measurements of the wound treated with combination of ADCs and bioengineered skin substitute exhibited significantly improved wound healing than untreated wounds or those that were treated with ASCs alone. Future research is warranted to examine the promising use of ADCs as treatment for chronic wounds.
Conclusion: Our bottom-up approach will integrate fundamental aspects of biomaterials design with cellular and molecular medicine to innovate an affordable and employable, novel system for the treatment of chronic wounds.
Biography:
Devashri Mukherjee has completed her Master’s in Public Health from the reputed Christian Medical College of Vellore in India. She is a Dental Surgeon by training and is presently working as an Associate Epidemiologist at the Bangalore office of Decision Resources Group India. She holds 10 international publications to her credit.
Abstract:
At Decision Resources Group, we specialize in forecasting trends in the global burden of diseases bolstered by extensive and comprehensive literature review. Atopic dermatitis, an inflammatory disease characterized by intense itching and eczematous lesions has become a common health problem affecting about 20% of children and 3% of adults worldwide. We base our report on the internationally accepted ISAAC Phase III results to which we retrofitted curves looking at historical data and developed a robust model to generate age and gender wise prevalence estimates for all ages. This model accounted for spontaneous remission as well as the birth cohort effect, which is the observed higher disease risk in children than adults. The ISAAC study results capture a uniform disease definition across all countries in our global estimates and allow for defensible and comparable rates of 12-month prevalence, lifetime prevalence and drug treatable population which we present across the North and South American, European, Asia Pacific, Middle East and African regions. We provide a snapshot of the worldwide prevalence indicating a worrisome rise in the low income countries but almost plateauing in the high income countries. Our report highlights the variation amongst the population eligible for drug treatment between high and low income countries. We also report the distribution of the disease based on its severity and atopic association. Combined with our ten year forecast, our results facilitate identification of countries at risk and enablement of opportunities for affordable promising therapies in those vulnerable countries.
Madalene C Y Heng
Professor of Medicine/Dermatology UCLA School of Medicine USA
Title: Phosphorylase kinase inhibition and removal of aggravating factors in the induction of long term remissions in psoriasis
Biography:
Madalene C Y Heng is a Clinical Professor of Medicine, Dermatology at the David Geffen UCLA School of Medicine. From 1979 to 2003, she was a Chief of Division of Dermatology, UCLA San Fernando Valley Medicine Program. She is currently in private practice in Heng Medical at Camarillo, CA and is a Reviewer for the Journal of the American Academy of Dermatology, American Journal of Geriatric Medicine, British Journal of Dermatology, Lancet, London, and International Journal of Angiology. She is the author of more than 140 scientific publications, including 78 published peer-reviewed articles on topics such as phosphorylase kinase activity and psoriasis, pathophysiology of common skin diseases, and wound healing.
Abstract:
Phosphorylase kinase (PhK) is a cyclic AMP-dependent dual specificity kinase capable of breaking down glycogen and phosphorylating both serine/threonine and tyrosine moieties in the activation of the transcription activator, NF-kB, which in turn is responsible for activating multiple genes responsible for inflammation and cell proliferation. Elevated PhK levels have been observed to correlate with increased phosphorylation and psoriatic activity, while suppression of PhK activity leads to resolution of psoriasis. Genes for psoriatic familial susceptibility have been mapped to 17q and psoriasis susceptibility loci to both 16q and 17q, apparently correlating with genes for the β-subunit of PhK (mapped to 16q) and the regulatory subunit for cAMP protein kinase (mapped to chromosome 17). These genetic findings provide some credence that defective inhibition of PhK activity may be responsible for its elevated activity in psoriasis. PhK is released within 5 minutes following injurious stimuli, including trauma, contact allergens and infections, which serve as aggravating factors in psoriasis. We have developed a protocol, consisting of inhibition of PhK by its selective inhibitor, curcumin, together with removal of aggravating factors to achieve not only total clearance of psoriasis, but also to produce long term remissions without the need for maintenance therapy. In this presentation, we include details of this combination therapy and identification of aggravating factors in our psoriatic patients.