Thank you, Jeffrey, and thank you to Steve and the Office of Rare Diseases for inviting me to be a part of this panel.
This is my son Sam Our story began 11 yrs ago when at the age of 2 years he was diagnosed with progeria.
Leslie …was to find the cause, treatment, and cure for Progeria
And this is where the heavy collaboration begins…. We asked ourselves what can we build to help people to help the children? To achieve our goals, our first steps were to identify the tools and resources essential to pushing the field forward. Researchers needed cells and tissues to conduct their research, so we created a cell and tissue bank and we send those cells and tissues to labs around the world. They needed money to conduct research, so we award research grants – 21 to date. We hold scientific meetings to bring scientists together to form collaborations. We built a medical records database that helps doctors and parents understand how to treat the children and optimize their quality of life. And perhaps most importantly, we formed a 20-scientist consortium to find the gene for Progeria.
PRF partners with Progeria families, academic institutions, and scientists to accomplish its scientific goals. We have received support from private US foundations and companies, volunteers who hold fundraisers, individuals who give donations, our volunteer board of directors, and many others. All of these logos and boxes represent just some of the people and organizations with whom we have established a relationship and that have provided support to PRF over the past 9 years. None of our work would be possible without them.
Leslie The Progeria gene finding led us to a drug treatment called FTI. This drug is extremely promising in preclinical studies. Here on the left you see a skin cell from a child without progeria. In the middle, you see a progeria skin cell. It is damaged, deformed, and will soon die. But in the last panel, we see a dramatic change in a progeria skin cell treated for just 36 hours with the FTI drug. The cell is normalized.
28 children from 16 countries are in the trial, and they come to Boston every 4 months for 2 years.
I’ve been asked to describe for you our experience at The Progeria Research Foundation with going from almost nothing, through discovery, and on to treatment, for an extremely rare disease, and in the meantime, probably discovering something new and important about aging in all of us. A key item for each step of the process has been collaboration.
Progeria Research Foundation at Partnering for Cures
Clues to Aging Through Progeria Research <ul><li>Leslie B. Gordon, MD, PhD </li></ul><ul><li>Medical Director, </li></ul><ul><li>The Progeria Research Foundation </li></ul><ul><li>Associate Professor, </li></ul><ul><li>Warren Alpert Medical School of Brown University and Hasbro Children’s Hospital , Providence, RI </li></ul><ul><li>Staff Scientist, </li></ul><ul><li>Children’s Hospital Boston and Harvard University, Boston, MA </li></ul>Audrey S . Gordon, Esq. President and Executive Director, The Progeria Research Foundation
<ul><li>Premature “Aging Disease” </li></ul><ul><li>Rare: frequency 1/4-8 million </li></ul><ul><li>Onset avg. 9 mo nths o ld </li></ul><ul><li>Uniformly Fatal </li></ul><ul><ul><li>CVD </li></ul></ul><ul><ul><li>average age 13 years </li></ul></ul>
1998 - There Was No Hope… <ul><li>No Research Funding, No Non-profit Driving Research </li></ul><ul><li>Was this a genetic disease? We did not know. </li></ul><ul><li>No Central Source of Clinical Information </li></ul><ul><li>No Treatment Prospects </li></ul><ul><li>No Place for Families and Physicians to go for help </li></ul>
1999: The Progeria Research Foundation <ul><li>Mission </li></ul><ul><ul><li>Cause </li></ul></ul><ul><ul><li>Treatment </li></ul></ul><ul><ul><li>Cure </li></ul></ul>www.progeriaresearch.org
Addressing the Needs of Scientists, Physicians, Families Cell/Tissue Bank : 111 Search For The Gene Consortium Established 2002 International Patient Registry/Medical Database: 79 HGPS Publications 2008 2000 1950 Research Funding : 27 Scientific Meetings: 5
Chapters, Individual Donors and Volunteers Partnerships create powerful forces for change! PreventionGenetics Private Foundations & Corporations Families
Normal Aging Nuclear defects Progeria and normal aging: We all make progerin Progerin Premature Aging Progeria Coronary Vessel 93-year-old Coronary Vessel
Progerin in N ormal A ging <ul><li>Progerin is expressed in normal fibroblast cultures at low levels compared to Progeria cultures (Scaffidi et al, 2005) </li></ul><ul><li>Progerin is expressed in normal skin biopsies, and biopsy microvasculature, and increases with age ( McClintock et al, 2007) </li></ul>
FTIs Normalize Progeria Cells Normal Fibroblast Progeria Fibroblast Progeria Fibroblast + FTI , 72 hrs. Capell et al 2005; Glynn et al, 2005; Toth et al, 2005; Young et al, 2005 FTIs Improved Disease in Progeria Mice Biology-based Treatment
May, 2007 the First-ever Treatment Trial Begins at Children’s Hospital Boston
From Gene Finding to Clinical Trial <ul><li>A Home Base for Children/Families/Physicians </li></ul><ul><li>Research-related Programs </li></ul><ul><li>Potential Treatment Based on Basic Biology </li></ul><ul><ul><li>In vitro and in vivo preclinical testing </li></ul></ul><ul><li>Expert Clinical Team </li></ul><ul><li>Drug Company Collaboration </li></ul><ul><li>Funding </li></ul>
Avenues for Treatments and Cure for Progeria Drug Development Pathway Based Basic Biology Stem Cell Therapy Gene Therapy Clinical Research
CMV Ex 11 Ex 12 GFP sv40 dsRed STOP A high-throughput drug screen for progeria Tom Misteli, PhD aberrant correct
Key Points <ul><li>Model for translational medicine </li></ul><ul><li>Clinical Treatment Possibilities </li></ul><ul><ul><li>Drug Development – </li></ul></ul><ul><ul><li>High Throughput Assay </li></ul></ul><ul><li>Implications for Aging and Atherosclerosis </li></ul><ul><li>Collaboration is Key </li></ul>
Thank you! <ul><li>Together, we WILL find the cure. </li></ul>