Clues to Aging Through Clues to Aging Through Progeria ResearchProgeria Research

Leslie Leslie B. B. Gordon, MD,Gordon, MD, PhDPhD• Medical Director, Medical Director, The Progeria Research FoundationThe Progeria Research Foundation

• Associate Professor,Associate Professor, Warren Alpert Medical School of Warren Alpert Medical School of Brown University Brown University and and Hasbro Hasbro Children’s HospitalChildren’s Hospital, Providence, RI, Providence, RI

•Staff Scientist,Staff Scientist, Children’s Hospital Boston and Children’s Hospital Boston and Harvard University, Boston, MAHarvard University, Boston, MA

Audrey SAudrey S. . Gordon, Esq.Gordon, Esq.President and Executive Director,President and Executive Director, The Progeria Research FoundationThe Progeria Research Foundation

• Premature “Aging Disease”Premature “Aging Disease”• Rare: frequency 1/4-8 millionRare: frequency 1/4-8 million• Onset Onset avg. avg. 9 mo9 monthsnths ooldld

• Uniformly FatalUniformly Fatal CVDCVD average age 13average age 13 years years

1998 - There Was No Hope…1998 - There Was No Hope…

•No Research Funding, No Non-profit Driving ResearchNo Research Funding, No Non-profit Driving Research•Was this a genetic disease? We did not know.Was this a genetic disease? We did not know.•No Central Source of Clinical InformationNo Central Source of Clinical Information•No Treatment ProspectsNo Treatment Prospects•No Place for Families and Physicians to go for helpNo Place for Families and Physicians to go for help

1999: The Progeria 1999: The Progeria Research FoundationResearch Foundation

Mission

Cause

Treatment

Cure

www.progeriaresearch.orgwww.progeriaresearch.org

Addressing the Needs of Scientists, Addressing the Needs of Scientists, Physicians, FamiliesPhysicians, Families

Cell/Tissue Bank: 111

Research Funding: 27

Scientific Meetings: 5

Search For The GeneConsortium Established 2002

International Patient Registry/Medical Database: 79

HGPS Publications

20082000

1950

Financial Profile: Income

The Progeria Research FoundationIncome Analysis - 2008

47%23%

30%

Special Events (includes chapter events,

PRF's Night of Wonder gala and annual road race, and

other volunteer fundraising)

Individual Giving

Private Foundations

TOTAL REVENUE: $1,210,367

Financial Profile: Expenses

The Progeria Research FoundationExpense Analysis - 2008

Research Programs 59%

Outreach and Education 7%

PRF Cell & Tissue BankMedical & Research

DatabaseDiagnostic Testing

Clinical Trial

Programs 87%

Administrative Expenses 13%

SUMMARY

Research Grant Funding 21%

Administrative Expenses (includes fundraising) 13%

Total Income:$1,210,367

Total Expenses:$1,086,583

Chapters, Individual Donors and Volunteers

Partnerships create powerfulPartnerships create powerfulforces for change!forces for change!

PreventionGenetics

Private Foundations & Corporations

Families

Normal AgingNormal Aging

NuclearNucleardefectsdefects

Progeria and normal aging: We all make progerin

ProgerinPremature AgingPremature Aging

Progeria Coronary Vessel

93-year-old Coronary Vessel

Progerin Progerin in in NNormal ormal AAgingging

Progerin is expressed in Progerin is expressed in normal fibroblast cultures at low normal fibroblast cultures at low levels compared to Progeria levels compared to Progeria cultures (Scaffidi et al, 2005)cultures (Scaffidi et al, 2005)

Progerin is expressed in Progerin is expressed in normal skin biopsies, and biopsy normal skin biopsies, and biopsy microvasculature, and increases microvasculature, and increases with age (with age (McClintockMcClintock et al, 2007) et al, 2007)

Normal Normal FibroblastFibroblast

Progeria Progeria FibroblastFibroblast

Progeria Progeria FibroblastFibroblast + +FTIFTI, 72 hrs., 72 hrs.

FTIs Normalize FTIs Normalize Progeria CellsProgeria Cells

Capell et al 2005; Glynn et al, 2005; Toth et al, 2005; Young et al, 2005Capell et al 2005; Glynn et al, 2005; Toth et al, 2005; Young et al, 2005

FTIs Improved FTIs Improved Disease in Disease in

Progeria MiceProgeria Mice

Biology-based TreatmentBiology-based Treatment

May, 2007 the First-ever Treatment Trial BeginsMay, 2007 the First-ever Treatment Trial Beginsat Children’s Hospital Bostonat Children’s Hospital Boston

From Gene Finding to Clinical TrialFrom Gene Finding to Clinical Trial

A Home Base for Children/Families/Physicians A Home Base for Children/Families/Physicians Research-related ProgramsResearch-related ProgramsPotential Treatment Based on Basic BiologyPotential Treatment Based on Basic Biology

In vitro and in vivo preclinical testingIn vitro and in vivo preclinical testingExpert Clinical Team Expert Clinical Team Drug Company Collaboration Drug Company Collaboration FundingFunding

Avenues for Treatments and Cure Avenues for Treatments and Cure for Progeriafor Progeria

Drug Development

Pathway BasedPathway Based

Basic BiologyBasic Biology

Stem Cell TherapyStem Cell Therapy

Gene TherapyGene Therapy

Clinical ResearchClinical Research

aberrant

correct

CMV Ex 11 Ex 12 GFP sv40 dsRedSTOP

A high-throughput drug screen for progeriaA high-throughput drug screen for progeria Tom Misteli, PhDTom Misteli, PhD

Key PointsKey Points

1.1. Model for translational Model for translational medicinemedicine

2.2. Clinical Treatment Clinical Treatment PossibilitiesPossibilities

Drug Development – Drug Development –

High Throughput AssayHigh Throughput Assay

3.3. Implications for Aging Implications for Aging and Atherosclerosis and Atherosclerosis

Collaboration is KeyCollaboration is Key

Thank you!Thank you!

Together, we WILL find the cure.Together, we WILL find the cure.