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 protected]

11th Symposium of LVMH Recherche

October 27, 2011, London UK

Slides: http://slideshare.net/LaBlogga

October 27, 2011DIYgenomics.orgOctober 27, 2011DIYgenomics.org 2

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

3

Image credit: http://www.hongkiat.com

October 27, 2011DIYgenomics.org

4

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


Agenda




5



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

6

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 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.

October 27, 2011DIYgenomics.org 8

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.; 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.


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

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.


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


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


Basal and squamous cell carcinoma


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)


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

17Source: 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, TIMP1) DNA damage repair response Subcutaneous fat thickness Overall aging response Other dermis and epidermis wellness

factors

18

Image credit: http://www.dnacustomizednutrition.com

1tissue 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)

19

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)

20

Image credit: Grice EA et al, Nat Rev Microbiol, 2011, Figure 3

Skin microbiome ecosystem distribution


Agenda




21



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

22

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

23

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

24

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

25Source: 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)

26

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)

27

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)

28Source: 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

29

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


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

30

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

31Source: http://www.biojouvance.com

Image credit: http://www.biojouvance.com

Bio-roller microneedle home therapy system


Agenda




32



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

33

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

34

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)

35

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

36

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

October 27, 2011DIYgenomics.org

37

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


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

translational antiaging skin research

Health & Medicine