New! Visit our “What’s News in Progeria Research” section
What’s News in Progeria Research
We’ve added this section so you can easily access information on the latest scientific publications on Progeria research. ENJOY!
Is Progeria Reversible?
Two recent publications show that FTIs and gene therapy may do just that!
August and October 2008: Two separate studies show that Progeria is reversible in the cardiovascular system and the skin of mouse models. The experiments were significant in not treating the mice until they expressed Progeria symptoms, whereas most previous studies began treatment before Progeria was apparent. Production of progerin (the damaging protein made from the Progeria gene) was inhibited either by treatment with a farnesyl transferase inhibitor (FTI) or by turning off the gene. In both cases the mice reverted to normal or almost normal conditions. These observations provide encouraging evidence for the current clinical trial of FTIs for Progeria.
In a stunning display of progress with the FTI drug – now being used in the First-ever Progeria Clinical Drug Trial – Dr. Francis Collins’ research team at the National Institutes of Health * found that FTI’s prevented and even reversed the most devastating effect of Progeria in mice: cardiovascular disease.* "We were amazed that [the drug] worked so well," says Francis Collins, a geneticist and former director of the National Human Genome Research Institute, who was senior author for the research team that identified the Progeria gene mutation in 2003. “Not only did this drug prevent these mice from developing cardiovascular disease, it reversed damage in mice that already had disease.”
The Progeria mice develop heart disease that mirrors that of children with Progeria. The authors found that the FTI was both able to prevent the development of heart disease to some degree when mice were treating from the time they were weaned, and partially reverse established disease when mice were treated beginning at age 9 months. “One of the striking things from my perspective was the ability to reverse disease, ” Collins said, which is critical given that Progeria is generally not diagnosed at birth, but only when children begin to show symptoms, when part of the damage already has been done.
"If these drugs are found to have similar effects in children, this could mark a major breakthrough for treating this devastating disease," said NHLBI’s Dr. Nabel, who was a co-author of the study. "In addition, these findings shed light on the potential role of FTI drugs to treat other forms of coronary artery disease."
View the article in Scientific American, “New Hope for Progeria: Drug for Rare Aging Disease”, at http://www.sciam.com/article.cfm?id=new-hope-for-progeria-drug-for-rare-aging-disease and the NIH press release at http://www.nih.gov/news/health/oct2008/nhgri-06.htm
* Capell, et. al, “A farnesyltransferase inhibitor prevents both the onset and late progression of cardiovascular disease in a Progeria mouse model.” Proceedings of the National Academy of Sciences, Vol. 105, no. 41, 15902-15907 (Oct. 14, 2008)
In a second study that was published online in the Journal of Medical Genetics**, Dr. Maria Eriksson’s research team at the Karolinska Institutet in Sweden created another mouse model of Progeria with abnormalities of the skin and teeth. The mice are genetically engineered so that the Progeria mutation can be shut off at any time. Once disease was apparent, the gene for Progeria was turned off. After 13 weeks the skin was almost indistinguishable from normal skin. This study shows that in these tissues the expression of the Progeria mutation does not cause irreversible damage and that the reversal of disease is possible, which gives promise for treatment for Progeria.
**Eriksson, et. al., “Reversible phenotype in a mouse model of Hutchinson-Gilford Progeria syndrome.” J. Med. Genet. published online 15 Aug 2008; doi:10.1136/jmg.2008.060772
To purchase this article, go to: http://jmg.bmj.com/cgi/rapidpdf/jmg.2008.060772v1
To purchase this article, go to: http://jmg.bmj.com/cgi/rapidpdf/jmg.2008.060772v1
More Evidence of the Link between Progeria and
Normal Aging and Heart Disease
The articles about these exciting studies all agree that beyond Progeria, these results have the potential to benefit all patients with cardiovascular disease. Researchers have discovered that the toxic protein responsible for Progeria is actually produced at low levels in all humans, possibly accumulating as we age. Thus, by studying these rare children, Collins says, we can further our understanding of a major mechanism of human aging—and perhaps, find new ways to slow the process.