Innovator Spotlight

Q: What prompted you to start your own foundation?
When my nephew Sam was diagnosed with Progeria in 1998, my family and I immediately collected as much information as we could find on the disease. We discovered that Progeria was a 100 percent fatal premature aging disease, but incredibly there was almost no progress being made to help the children. There was no way to definitively test for the disease, no funding for Progeria research, and no organization advocating for children with Progeria. We recognized the need to fill that void – to take these children out of the background where they had been for more than 100 years, and put them and Progeria at the forefront of scientific efforts. So in 1999, we gathered family, friends, and colleagues and established the Progeria Research Foundation (PRF). With the support of hundreds of volunteers, we have the opportunity to drive medical and research programs that push the field of Progeria forward towards discovery, treatments, and cure.

PRF has made remarkable progress in a brief period of time. Despite the fact that Progeria is one of the rarest diseases on earth, and we had to start from ground zero, in our short, 11-year history we have achieved the Progeria gene discovery, first-ever clinical drug trials, an enormous growth in knowledge of and interest in the field, and worldwide awareness of the disease and PRF’s work. We have also solidified biological links between Progeria, heart disease, and aging. This is due in large part to PRF’s creation of all the research-related tools and programs needed to advance toward a cure for Progeria, including the Cell & Tissue Bank, Diagnostic Testing, Medical & Research Database, grant funding, scientific workshops, International Registry, and Translation and Public Awareness programs.

Q: What do you think have been your biggest research achievements?
In 2003, The Progeria Research Foundation’s collaborative research team, including Dr. Francis Collins, discovered the Progeria gene mutation – the cause of Progeria. It lies within a gene called LMNA (lamin-A). We discovered that the LMNA gene is producing an abnormal protein called progerin, that we never knew existed. The Progeria gene discovery literally flung open the doors of science for the field of Progeria, for the children, and for the field of aging research. This discovery helped us to understand how we can learn about Progeria through studying heart disease and aging – and we can discover keys to heart disease and aging through understanding Progeria. It’s amazing. By studying one of the rarest diseases on earth, we are learning a tremendous amount about ourselves.

Q: What are your goals for 2011, and what will it take to get you to realize these goals?

  • Continue to forge ahead with analyzing the progeria treatment trial data, and discover whether the treatments are working to help the children.
  • Establish a Progeria Center of Excellence, so that there is a central place for children to go for expert clinical care.
  • Continue our efforts to promote drug discovery and partnership with drug companies to develop potential treatments and the cure for Progeria.
  • Continue our partnership with Spectrum and GlobalHealthPR, and expand the Find the Other 150 Campaign to other countries, to increase awareness of Progeria so more children will be found and helped by PRF.
  • Increase the number of participants in the International Registry, Cell & Tissue Bank, and Medical & Research Database projects, so that scientists can continue to use them as research tools to understand Progeria, heart disease, and aging.
  • Fund additional research proposals that focus on studying the Progeria gene and how this defect can be corrected.

Expansion of our volunteer base, staff and revenue will help us realize the above goals.

Q: Can you tell us about the clinical trials you have been the driving force behind?
To date, PRF has funded and co-coordinated three clinical trials:

  1. In 2006, after only seven years in existence, we became scientifically ready to begin the first-ever Progeria clinical drug trial with a drug that shows great promise to effectively treat children with Progeria. The drug is called a farnesyltransferase inhibitor, or FTI, and here’s how it works. The protein responsible for Progeria is called progerin. In order to block normal cell function and cause Progeria, a molecule called a “farnesyl group” must be attached to the progerin protein. FTIs act by blocking (inhibiting) the attachment of the farnesyl group onto progerin. This is how FTIs work on progerin to make it less toxic, and how we hope to improve disease for children with Progeria. For the first time, we have in front of us a possible treatment for children with Progeria. This trial began in May 2007, with 28 children, ages 3 to 15 years, flown in to Children’s Hospital Boston from 16 different countries. We look forward to trial results on this exciting treatment.
  2. The Feasibility Trial: Researchers have identified two additional drugs that, when used in combination with the current FTI drug being tested, may provide an even more effective treatment for children with Progeria than FTIs alone. The trial team conducted a mini-trial for five children with Progeria, to determine if a three-drug combination of FTI, pravastatin, and a bone drug called zoledronate would be well-tolerated, prior to embarking on a larger trial. The drugs were well tolerated, paving the way for the full, two-year, Triple Drug Trial.
  3. The Progeria Triple Drug Trial is a much larger trial, including 45 children from 24 countries, speaking 17 languages. This trial adds two drugs, called pravastatin and zoledronate, to the current treatment with FTI. With the larger group of participants, we can ask about whether the three-drug combination improves disease in Progeria. All three drugs target different points along the pathway leading to production of the disease-causing progerin. We hope that the drugs will work as partners, to complement each other so that the progerin protein is “paralyzed” and therefore less toxic. 

Q: What is the significance of progress in Progeria research for the rest of us?
All children diagnosed with Progeria die of the same heart disease that affects millions of normal aging adults (atherosclerosis), but instead of experiencing a potentially fatal heart attack or stroke at age 60 or 70 , these children may suffer the same stroke or heart attack at ages 5 or 6. The scientifically proven connection of Progeria to common heart disease and aging has far-reaching implications for millions: The Progeria gene discovery revealed that Progeria is caused by a protein called progerin, the same protein produced at much lower levels by healthy individuals and that builds normally over a lifetime as people age. Thus researchers have confirmed the link between normal aging, heart disease, and Progeria, so finding the cure will help not only these special children, but perhaps also those who suffer from heart attacks, strokes, and other aging-related conditions.