In just 10 years, since we founded PRF and there were no resources for these children, we have gone from gene finding to the first clinical trials in Progeria. We are now being hailed as a model for disease-research organizations. and a prime example of successful translational research, moving from the lab to treatments at a pace virtually unheard of in the scientific community. And while helping this handful of children, the connection of Progeria to common heart disease and aging has tremendous implications for us all.

To date, PRF has funded and co-coordinated three clinical trials: the first ends December 2009, the second was a 1-month trial in March 2009 to determine if we could move forward with a larger population, which we did and that newest trial began August 2009.

 Announcing the Progeria Triple Drug Trial

 
May 7, 2007 - December 2009: First-Ever Progeria Clinical Drug Trial Marks Historic Moment in Progeria Research History!

After only 7 years in existence, we became scientifically ready to begin this trial with a drug that shows great promise to effectively treat children with Progeria, and in the process we may help millions of older people who suffer from heart disease and other, aging-related conditions.

Researchers have now identified a potential drug treatment for children with Progeria, called FTIs.  For the first time, we have in front of us a possible treatment for children with Progeria. Exciting times!

 

The Progeria clinical drug trial began on May 7th, 2007 with two children arriving in Boston, MA for their first of seven visits over a 2-year period. At this first visit, they were given extensive tests and their first doses of the drug. An average of two families have been flying to Boston each week since then, and in October 2007, the trial became fully enrolled. The trial is expected to end in October 2009, with results published in 2010. 

 

Megan proudly wears her 1-year Trial Medal, which she received at the end of her May 2008 trip to Boston

 

 

 

 

“I know of no other rare genetic disease that has gone from gene discovery to clinical trial in under four years - a phenomenal testament to the hard work of The Progeria Research Foundation.”    Francis Collins, MD, PhD, Director of the National Human Genome Research Institute that mapped the human genome, workshop speaker and co-discoverer of the Progeria gene.

 

 

 

 

 

 

 

 

 

 

Julieta, from Argentina.

Twenty-eight (28) children from sixteen countries are participating, ages 3 to 15 years. Children return to Children’s Hospital Boston every four months, for testing and to receive new drug supply, and stay in Boston for 4-8 days each visit.  While at home, their doctors keep a close watch over the children and submit periodic health reports to the Boston research team.  For the duration of the trial, an average of 2 children per week are traveling to Boston to participate. 

 

“The two Megans”, both 6 years old, in Boston for the clinical trial in May 2007.

Children Originate from the Following Countries:  Argentina Belgium Canada Denmark England India Israel Italy Japan Mexico Pakistan Poland Portugal Romania USA Venezuela

Michiel, 8 ½ , from Belgium with Hayley, 9 ½ , from England in June 2007 at Children’s Hospital Boston during their first visit.

The Progeria Clinical Research Drug Trial:

What will the trial cost PRF?  We estimate the trial will cost PRF $2 million dollars. This will pay for clinical testing, translators, travel, food, lodging, and certain medical costs during that 2 ½ year time period.  Thanks to our many supporters, PRF raised the money needed to fund the trial!

 

 Click here to learn more about the science behind the clinical trial

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Announcing the Progeria Triple Drug Trial

The Progeria Research Foundation and Children’s Hospital Boston are once again partnering to conduct a second clinical trial for children with Progeria. This exciting and much larger trial will include up to 45 children from 19 different countries!

Summary: 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 FTI’s alone.

Scientific Basis for Treatment
Progeria is caused by an abnormal protein named progerin. The Progeria research team at Children’s Hospital Boston will add two drugs, called pravastatin and zoledronate, to the current treatment with FTI.

Strategy: All three drugs will target different points along the pathway leading to production of the disease-causing progerin. In exciting laboratory studies presented by Dr. Carlos Lopez-Otin of Spain at the 2007 Progeria Research Foundation Scientific Workshop, the two new drugs improved disease in Progeria cells and extended lifespan in mouse models of Progeria.

Goal: If the three drugs administered in this trial can effectively block this farnesyl group attachment, then progerin may be “paralyzed” and Progeria may be improved. We hope that the drugs will work as partners, to complement each other so that the progerin protein is affected more by combining the three drugs than using any one drug alone.

Who Will Enroll In The Triple Drug Trial?
The Feasibility Trial: The team has already conducted a mini-trial for 5 children with Progeria. The short, one month “feasibility” trial, asked whether the three-drug combination would be well-tolerated, prior to embarking on a larger international trial. Side effects were acceptable, and the team has moved ahead to the larger efficacy trial.
The Efficacy Trial: We anticipate up to 45 children will enroll in this trial, from 19 different countries, speaking 11 different languages. This includes children participating in the FTI-only trial, the 5 in the feasibility trial, and other children that were either too young to participate in the first trial or children that we’ve discovered over the past 2 years. Children currently enrolled in the FTI-only trial will have the opportunity to enroll in the triple trial when they arrive for their last visit for the current trial. This allows the children to continue taking FTI without any missed doses.

The Treatment/Progeria Relationship
How did we get from gene discovery to drug therapy for children with Progeria? Finding the gene for Progeria was the key. This gene is called LMNA, and it normally encodes a protein called prelamin A (this protein is further processed and becomes lamin A). Children with Progeria have a mutation in LMNA which leads to the production of an abnormal form of prelamin A called “progerin.” Many years’ worth of basic research on prelamin A and lamin A gave us the ability to understand that the drugs administered in this trial may affect disease in Progeria. Over the past six years, research has focused on systematically testing these drugs on Progeria cells and Progeria mice.

The Clinical Trial Team
Since May 2007, a 28-member team has treated children with Progeria from around the globe. Members of the team have expertise not only in Progeria, but also in the three drugs administered in this trial.

Trial Medications at a Glance

Pravastatin (marketed as Pravachol or Selektine) is a member of the drug class of statins. It is usually used for lowering cholesterol and preventing cardiovascular disease.
Zoledronic acid is a bisphosphonate, usually used as a bone drug for improving osteoporosis, and to prevent skeletal fractures in people suffering from some forms of cancer.
Lonafarnib is an FTI (Farnesyltransferase inhibitor), a drug that can reverse an abnormality in Progeria cells in the laboratory, and has improved disease in Progeria mice.
All 3 drugs block the production of the farnesyl molecule that is needed for progerin to create disease in Progeria.

Timing
Patients will travel to Boston for testing and examinations lasting 4-7 days, every 6 months for a period of 2 years. For the FTI-only trial, Boston visits occur every four months.

Cost
We estimate the trial will cost PRF nearly $1.7 million over a 2 ½-year period for drugs, clinical testing, translators, travel, food, lodging and staff. Click here to donate to the triple drug trial and help make the GOAL of treatment and cure a REALITY!

* “Combined treatment with statins and aminobisphosphonates extends longevity in
a mouse model of human premature aging”,by Ignacio Varela, Sandrine Pereira, Alejandro P. Ugalde, Claire L. Navarro, Marıa F. Suarez, Pierre Cau, Juan Cadinanos, Fernando G. Osorio, Nicolas Foray, Juan Cobo, Felix de Carlos, Nicolas Levy, Jose MP Freije and Carlos Lopez-Otın. Nature Medicine, 2008. 14(7): p. 767-72.

The new generation of children PRF is helping…
In March, 2009, five children, ages 2-3, participated in a one-month feasibility study to determine if the side effects of the three drugs taken together were tolerable. The results were positive, paving the way for the full, two-year, Triple Drug Trial to enroll up to 45 children with Progeria. Hats off to these amazing families!

Here is what some of them had to say:


“EVERYONE has been so wonderful. To us you are ALL GOD SENT and we APPRECIATE all that you do for these little angels. Our family is so overwhelmed with excitement and all sorts of emotions with Adalia’s trip to Boston this weekend, I can’t even begin to type the words of how we are feeling”.

Cam and his dad learn how to mix the FTI drug with a sweetener.

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