Translational antiaging skin research

Translational anti-aging skin research: latest advances, personal genomics, and product research opportunities Melanie Swan Founder DIYgenomics +1-650-681-9482 @DIYgenomics www.DIYgenomics.org [email_address] 11th Symposium of LVMH Recherche October 27, 2011, London UK Slides: http://slideshare.net/LaBlogga

About Melanie Swan
Founder DIYgenomics, futurist and applied genomics expert
Work experience: Fidelity, JP Morgan, iPass, RHK/Ovum, Arthur Andersen
Education: MBA Finance, Wharton, University of Pennsylvania; BA French and Economics, Georgetown University
Sample publications:
Source: http://melanieswan.com/publications.htm
Swan M. Meeting Report: American Aging Association 40(th) Annual Meeting, Raleigh, North Carolina, June 3-6, 2011. Rejuvenation Res . 2011, Aug;14(4):449-55.
Swan, M., Hathaway, K., Hogg, C., McCauley, R., Vollrath, A. Citizen science genomics as a model for crowdsourced preventive medicine research. J Participat Med . 2010, Dec 23; 2:e20.
Swan, M. Multigenic Condition Risk Assessment in Direct-to-Consumer Genomic Services. Genet. Med. 2010 , May;12(5):279-88.
Swan, M. Translational antiaging research. Rejuvenation Res. 2010 , Feb;13(1):115-7.
Swan, M. Engineering Life into Technology: the Application of Complexity Theory to a Potential Phase Transition of Intelligence. Symmetry 2010 , 2, 150:183.
Swan, M. Emerging patient-driven health care models: an examination of health social networks, consumer personalized medicine and quantified self-tracking. Int. J. Environ. Res. Public Health 2009 , 2, 492-525.

Agenda
Top 10 translational anti-aging skin research advances
Role of personalized genomics
Skin disease profiling
Skin wellness profiling
Skin care product response
Wrinkles: potential causes and translational remedies
Other translational anti-aging skin advances
Image credit: http://www.hongkiat.com

Top 10 anti-aging skin research advances Botox substitutes Skin microbiomics 3-D skin printing Next-generation skin grafting Cellular therapies Genomic disease profiling Genomic product profiling Retinoids and substitutes Spray-on skin Stem cell facelift 2020 2010 2015 Image credit: http://www.dreamstime.com

Agenda

Personalized genomics and skin research
Using genetic sequencing profiles of individuals in health and wellness decisions
Multilevel analysis
Whole human sequencing, SNP mutations, structural variation, epigenomics, RNA expression, microbiome integration
Consumer cost = $99
International availability
100,000+ subscribers
Image credit: http://snpsinfo.synthasite.com SNP mutation

Numerous useful applications of genomics
Ancestry
Carrier status (pregnancy)
Identity (paternity, forensics)
Drug response
U.S. FDA has validated genomic biomarkers for 75 drugs (July 2011) 1
Disease risk
Criticism re: validity and utility 2
Image credit: http://www.uchsc.edu 1 Source: http://www.fda.gov/Drugs/ScienceResearch/ResearchAreas/Pharmacogenetics/ucm083378.htm 2 Source: Swan M. Multigenic condition risk assessment in direct-to-consumer genomic services. Genet Med. 2010 May;12(5):279-88.

Personal genome results

Drug response

Example: what to do with your data
Check if you have the risk allele for the BDNF gene
Determine related SNP/rsID#, rs6265 (neuroplasticity)
Search genomic data for rs6265 genotype (e.g., CC)
Determine the risk allele (which letter?) (e.g.; G 1 )
Current genomics search resources
PharmGKB, dbSNP, GWAS catalog, SNPedia
Source: http://www.wired.com/wiredscience/2009/10/genetically-bad-driving 1 Ribeiro, L. et. Al., The brain-derived neurotrophic factor rs6265 (Val66Met) polymorphism and depression in Mexican-Americans. Cellular, Molecular and Developmental Neuroscience. May 8, 2007.

Finding your BDNF data, variant rs6265
Consumer genomic services genotype 1 million variants but only map a few up to the annotation browser

Health optimization studies
Goal: realize predictive preventive medicine
Optimize individualized care and product recommendations
Generalized hypothesis
One or more polymorphisms may result in out-of-bounds baseline levels of phenotypic markers. These levels may be improved through personalized intervention.
Skin study examples: TERC & TERT/telomere-length, IL1A and TNF genes/Retin-A reaction
Source: Swan, M., Hathaway, K., Hogg, C., McCauley, R., Vollrath, A. Citizen science genomics as a model for crowdsourced preventive medicine research. J Participat Med. 2010, Dec 23; 2:e20.
Genotype Phenotype Intervention Outcome + + =

Genomic disease profiling: skin cancers
Melanoma: 20% heritability (vs. 33% non-skin cancers)
Source: DIYgenomics Consumer genomic service coverage of skin cancer conditions

Personalized genetic risk for melanoma Source: DIYgenomics, Swan M. Multigenic condition risk assessment in direct-to-consumer genomic services. Genet Med. 2010 May;12(5):279-88. Polygenic risk analysis for melanoma

Basal and squamous cell carcinoma Source: DIYgenomics Polygenic risk analysis for basal cell carcinoma Polygenic risk analysis for squamous cell carcinoma

Genomic profiling for other skin disease
Skin irritation disease
Acne, eczema (atopic dermatitis), irritation, dryness, psoriasis, erythema
Sun damage and pigmentation
Sun damage, premature aging, freckles, xeroderma pigmentosa, solar lentigo, skin lesions, vitiligo
Rare genetic and other skin disease
Cockayne syndrome, Kindler syndrome, Dupuytren's disease, scleroderma (limited cutaneous type), keloid (scarring)
Source: DIYgenomics Image credit: http://www.umich.edu

Genomic disease profiling in hair conditions
Hair loss, male pattern baldness, alopecia areata
Premature hair graying
Hair thickness and curliness
Source: DIYgenomics, https://www.23andme.com/health/Male-Pattern-Baldness/techreport/

Genomic wellness profiling in skin
Predictive indicator for which skin conditions may arise over time
Areas of genomic wellness profiling
Cancer: oncogenes and tumor suppressors
Immune system response (photo-damage: melanin production, p53, TIMP 1 )
DNA damage repair response
Subcutaneous fat thickness
Overall aging response
Other dermis and epidermis wellness factors
Image credit: http://www.dnacustomizednutrition.com 1 tissue inhibitor of metalloproteinases

Genomic product response profiling in skin
Personalized product recommendations
Predicted response
Efficacy
Side effects
Skin care products with genomic associations
Tretinoin (P&G, Kaczvinsky JR et al, Skin Therapy Lett, 2011)
Antioxidant treatment
Anti-aging DHEA treatment
Aluminum powder
Mosquito repellent ( microbiomics) ( Verhulst NO et al, FEMS Microbiol Ecol, 2010)
Image credit: http://www.dkorean-beauty.com

Skin microbiome profiling
Bacterial colonization influenced by host and environment
2-way immune response
Microbiota educates immune system
Cutaneous innate and adaptive immune responses modulate skin microbiota
Novel promicrobial and antimicrobial treatments ( Grice EA et al, Nat Rev Microbiol, 2011)
Image credit: Grice EA et al, Nat Rev Microbiol, 2011, Figure 3 Skin microbiome ecosystem distribution

Agenda

Wrinkle formation: potential causes
Sun damage and UV-radiation
Activation of heparanase (an extracellular matrix (ECM) degradation molecule
Loss of subcutaneous fat
Fibrosis
Tissue thickened and loosened from ECM proteins
Telomere shortening
Photo-damage reduces telomere length and increases reactive oxygen species (ROS) production
Image credit: http://cfps.gorillartsgroup.com Loss of subcutaneous fat with aging

Wrinkles: potential translational solutions
Topical treaments
Retinoids
Retinoid substitutes
Salicin
CoQ10
Intense pulsed light (IPL) treatment for photo-aging
Cellular therapies
LaViv fibroblast culturing and nasolabial injection
Facial fat transfer / stem cell facelift
Fillers (e.g.; botox) and substitutes
Transdermal hexapeptides and microneedle array
Image credit: http://www.stockpodium.com

Topical treatment of wrinkles - retinoids
Any of various natural or synthetic derivatives of vitamin A
Retinol, retinaldehyde, adapalene, tretinoin, isotretinoin, tazarotene
Retin-A is a popular tretinoin product
Image credit: http://www.skinacea.com/retinoids/types-of-retinoids.html

DIYgenomics Retin-A skin cream study
Widely-used Retin-A often produces side-effects
Source: http://genomera.com/studies/retin-a-wonder-cream-for-acne-and-wrinkles-is-there-a-genomic-link

Retinoid substitutes
Retinoid limitations
Photo-unstable and skin irritation
Retinyl retinoate (a novel hybrid retinoid)
An ester of all-trans retinoic acid (RA) and all-trans retinol
Reduced toxicity due to blocking carboxyl end group of RA
Higher skin regeneration activity than with retinol
Increases the stability of retinol which may have an anti-wrinkle effect ( Kim H et al, Br J Dermatol, 2010 )
Retinyl N-formyl aspartamate
A synthesized photostable retinol derivative with a similar effect on collagenase expression level as retinol (Lee MS et al, J Am Acad Dermatol, 2006)
Image credit: http://www.enprani.com Enprani retinyl retinoate-based product

Additional topical treatments of wrinkles
Salicin (willow bark-derived anti-inflammatory)
Activates heat shock proteins (HSPs) which protect cells from stress-induced damage (Gopaul R et al, J Cosmet Dermatol, 2010)
CoQ10
Reduces reactive oxygen species (ROS) production and DNA damage triggered by UV-radiation (Inui M et al, Biofactors, 2008)
Intense pulsed light (IPL) treatment for photo-aging
Prevents telomere shortening and decreases ROS (Wang R et al, Photomed Laser Surg, 2011)
Image credit: http://www.luckyvitamin.com

DIYgenomics TA-65 study
Skin benefits: look younger, improved wound healing, less sleep but improved quality (de Jesus BB et al, Aging Cell, 2011; Harley CB et al, Rejuvenation Res, 2011)
Source: http://genomera.com/studies/aging-telomere-length-and-telomerase-activation-therapy

Cellular therapies for wrinkles
LaViv (azficel-T) 1 - Fibrocell Science (Exton PA)
Approved June 2011
Collagen-producing fibroblasts biopsied from behind the ear and cultured for 90 days
Injected into smile line wrinkles
Longer-lasting than absorbable fillers
VAVELTA, Intercytex (Manchester UK)
Human dermal fibroblasts for skin repair and rejuvenation
1 Source: Schmidt C. FDA approves first cell therapy for wrinkle-free visage. Nat Biotechnol. 2011 Aug 5;29(8):674-5. Image credit: http://www.consultingroom.com

Facial fat transfer / stem cell facelift
Fat removed via liposuction, stem cells harvested from fat, treated, and injected into the face
Anti-wrinkle treatment
Nasolabial fold and glabellar furrows
Stem cells combined with hyaluronic acid (HA) were able to fill in deep folds (Claudio-da-Silva C et al, Rev Col Bras Cir, 2009)
Improved skin tone and decreasing lines of expression
Image credit: http://www.thebeautyrules.com

Aesthetic dermatology treatments
Traditional filler injections: botox and hyaluronic acid (HA)
Botox alternative Bio Choice
No-needle transdermal delivery
Skin patches saturated with acetyl hexapeptide (Argireline from Lipotec)
Lines smooth with moisture-binding ingredients
Local disruption of nerve signals (like botox)
Bio-roller microneedle therapy
Non-surgical wrinkle treatment
Stimulate collagen and elastin production
Source: http://www.biojouvance.com Image credit: http://www.biojouvance.com Bio-roller microneedle home therapy system

Agenda

Other areas of translational skin research
Regenerative medicine technology translation: military use to aesthetic enhancement
Dermal substitutes and next-generation skin grafting
Wound-healing and scar reduction
Spray-on skin
Images credit: http://www.stratatechcorp.com StrataGraft dermal substitute

Dermal substitutes/next-generation grafting
Apligraf (Organogenesis, Canton MA)
Allogeneic cell-based epidermis formed in 20 days
Dermagraft (Advanced BioHealing, Westport CT)
Cryopreserved dermal substitute derived from human fibroblasts, extracellular matrix, and a bioabsorbable scaffold
PermaDerm (Regenicin/Lonza, Little Falls NJ)
Autologous tissue-engineered epidermis and dermis in 30 days
Cultured fibroblast and kerotinocytes on an absorbable collagen substrate (biomedical polymer)
StrataGraft (Stratatech, Madison WI)
Epidermal and dermal skin substitute
Human keratinocyte progenitor cell line
Image credit: http://www.regenicin.com PermaDerm

Wound-healing and scar reduction
KeraHeal (KeraNetics, Winston-Salem NC)
Keratin gel for burn repair; burn dressing and bandages
Neodyne (Neodyne Biosciences, Menlo Park CA)
Bandage for improved healing and scar reduction
Reducing scarring by controlling the mechanical environment (Gurtner GC et al, Ann Surg, 2011)
Skin stretching for burn repair to avoid scarring
(Verhaegen PD et al, Plast Reconstr Surg, 2011)
Neodyne scar prevention 'Band-Aid' Image credit: http://www.internalmedicinenews.com

Spray-on skin
Skin-cell Gun (Joerg C. Gerlach, Univ Pittsburg) 1
An aerosol system to spray on cultured skin cells
ReCell spray-on skin (Avita Medical, Cambridge UK)
Autologous cells sprayed in 30-minute on-site procedure
Skin-spraying project (James Yoo, Wake Forest Univ)
3-D laser images of would calculate layers of skin to spray
1 Source: http://www.physorg.com/news/2011-02-skin-cell-gun-drastically.html Image credit: http://www.avitamedical.com ReCell Image credit: http://inhabitat.com/skin-cell-spraying-bio-printer-can-heal-burn-victims-in-three-weeks 3-D wound scanner and skin modeling

Top 10 anti-aging skin research advances Botox substitutes Skin microbiomics 3-D skin printing Next-generation skin grafting Cellular therapies Genomic disease profiling Genomic product profiling Retinoids and substitutes Spray-on skin Stem cell facelift 2020 2010 2015 Image credit: http://www.dreamstime.com

Summary
Exciting translational anti-aging skin innovations
Personalized genomic profiling
Skin disease, wellness, and product response
Commercialization of potential anti-wrinkle remedies
Topical treatments (retinoids, substitutes, Salicin, CoQ10, laser), cellular therapies, botox/filler substitutes
Technology translation: military to aesthetic
Dermal substitutes, anti-scarring wound-healing, spray-on skin
Image credit: http://www.drbaileyskincare.com

Merci! Melanie Swan Founder DIYgenomics +1-650-681-9482 @DIYgenomics www.DIYgenomics.org [email_address] Slides: http://slideshare.net/LaBlogga Creative Commons 3.0 license Collaborators: Lorenzo Albanello Janet Chang Cindy Chen John Furber Eri Gentry Kristina Hathaway Takashi Kido Laura Klemme Lucymarie Mantese Raymond McCauley Louis Nahum Marat Nepomnyashy Ted Odet Roland Parnaso William Reinhardt Greg Smith Aaron Vollrath Lawrence S. Wong Crowd-sourced clinical trials Personal genome apps

Translational antiaging skin research

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