Translational antiaging skin research
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Transcript of 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
11th Symposium of LVMH Recherche
October 27, 2011, London UK
Slides: http://slideshare.net/LaBlogga
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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.
October 27, 2011DIYgenomics.orgOctober 27, 2011DIYgenomics.org
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
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Image credit: http://www.hongkiat.com
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Top 10 anti-aging skin research advances
Botox substitutes
Skin microbiomics
3-D skin printingNext-generation
skin grafting Cellular therapies
Genomic disease profiling
Genomic product profiling
Retinoids and substitutes
Spray-on skin
Stem cell facelift
20202010 2015
Image credit: http://www.dreamstime.com
October 27, 2011DIYgenomics.orgOctober 27, 2011DIYgenomics.org
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
5
Image credit: http://www.hongkiat.com
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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
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Image credit: http://snpsinfo.synthasite.com
SNP mutation
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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 utility2
Image credit: http://www.uchsc.edu
1Source: http://www.fda.gov/Drugs/ScienceResearch/ResearchAreas/Pharmacogenetics/ucm083378.htm2Source: Swan M. Multigenic condition risk assessment in direct-to-consumer genomic services. Genet Med. 2010 May;12(5):279-88.
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Personal genome results
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Drug response
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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.; G1) Current genomics search resources
PharmGKB, dbSNP, GWAS catalog, SNPedia
Source: http://www.wired.com/wiredscience/2009/10/genetically-bad-driving1Ribeiro, L. et. Al., The brain-derived neurotrophic factor rs6265 (Val66Met) polymorphism and depression in
Mexican-Americans. Cellular, Molecular and Developmental Neuroscience. May 8, 2007.
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Finding your BDNF data, variant rs6265
Consumer genomic services genotype 1 million variants but only map a few up to the annotation browser
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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
Genotype Phenotype Intervention Outcome+ + =
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.
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Genomic disease profiling: skin cancers
Melanoma: 20% heritability (vs. 33% non-skin cancers)
13Source: DIYgenomics
Consumer genomic service coverage of skin cancer conditions
Cancer condition 23andMe deCODEme Navigenics* Pathway*1 Basal Cell Carcinoma X X2 Cutaneous Melanoma/Melanoma X X X3 Squamous Cell Carcinoma X
3 1 1 1
Total conditions reviewed 208 49 40 71Service price to consumers (October 10, 2011) $ 99 $ 2,000 $ 999 $ 299
*Not truly direct-to-consumer, only available through physicians
Sources:
https://www.23andme.com/health/all
http://demo.decodeme.com/health-watch
http://www.navigenics.com
http://www.pathway.com/dna-reports/full-list-of-conditions
Company
Consumer genomic service coverage of skin cancer conditions
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Personalized genetic risk for melanoma
14Source: 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
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Basal and squamous cell carcinoma
15Source: DIYgenomics
Polygenic risk analysis for basal cell carcinoma
Polygenic risk analysis for squamous cell carcinoma
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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)
16Source: DIYgenomics
Image credit: http://www.umich.edu
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Genomic disease profiling in hair conditions
Hair loss, male pattern baldness, alopecia areata Premature hair graying Hair thickness and curliness
17Source: DIYgenomics, https://www.23andme.com/health/Male-Pattern-Baldness/techreport/
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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, TIMP1) DNA damage repair response Subcutaneous fat thickness Overall aging response Other dermis and epidermis wellness
factors
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Image credit: http://www.dnacustomizednutrition.com
1tissue inhibitor of metalloproteinases
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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)
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Image credit: http://www.dkorean-beauty.com
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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)
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Image credit: Grice EA et al, Nat Rev Microbiol, 2011, Figure 3
Skin microbiome ecosystem distribution
October 27, 2011DIYgenomics.orgOctober 27, 2011DIYgenomics.org
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
21
Image credit: http://www.hongkiat.com
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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
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Image credit: http://cfps.gorillartsgroup.com
Loss of subcutaneous fat with aging
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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
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Image credit: http://www.stockpodium.com
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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
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Image credit: http://www.skinacea.com/retinoids/types-of-retinoids.html
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DIYgenomics Retin-A skin cream study
Widely-used Retin-A often produces side-effects
25Source: http://genomera.com/studies/retin-a-wonder-cream-for-acne-and-wrinkles-is-there-a-genomic-link
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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)
26
Image credit: http://www.enprani.com
Enprani retinyl retinoate-based
product
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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)
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Image credit: http://www.luckyvitamin.com
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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)
28Source: http://genomera.com/studies/aging-telomere-length-and-telomerase-activation-therapy
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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
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1Source: 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
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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
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Image credit: http://www.thebeautyrules.com
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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
31Source: http://www.biojouvance.com
Image credit: http://www.biojouvance.com
Bio-roller microneedle home therapy system
October 27, 2011DIYgenomics.orgOctober 27, 2011DIYgenomics.org
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
32
Image credit: http://www.hongkiat.com
October 27, 2011DIYgenomics.orgOctober 27, 2011DIYgenomics.org
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
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Images credit: http://www.stratatechcorp.com
StrataGraft dermal substitute
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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
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Image credit: http://www.regenicin.com
PermaDerm
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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)
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Neodyne scar prevention 'Band-Aid'
Image credit: http://www.internalmedicinenews.com
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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
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1Source: 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
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Top 10 anti-aging skin research advances
Botox substitutes
Skin microbiomics
3-D skin printingNext-generation
skin grafting Cellular therapies
Genomic disease profiling
Genomic product profiling
Retinoids and substitutes
Spray-on skin
Stem cell facelift
20202010 2015
Image credit: http://www.dreamstime.com
October 27, 2011DIYgenomics.orgOctober 27, 2011DIYgenomics.org
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
38
Image credit: http://www.drbaileyskincare.com
Merci!
Melanie SwanFounder
DIYgenomics+1-650-681-9482
@DIYgenomicswww.DIYgenomics.org
[email protected]: http://slideshare.net/LaBloggaCreative 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
Crowd-sourced clinical trialsPersonal genome apps
Marat Nepomnyashy
Ted Odet
Roland Parnaso
William Reinhardt
Greg Smith
Aaron Vollrath
Lawrence S. Wong