Hutchinson-Gilford Progeria Syndrome (Progeria) is an extremely rare, fatal, segmental premature aging syndrome caused by a genetic mutation. Without treatment, death occurs at an average age of 14.6 years.
Two and half years ago, the progeria community lost one of its greatest advocates – Sam Berns – to the disease. A clip of his TED Talk is at the end of this article. While Sam is no longer with us, the foundation he inspired – the Progeria Research Foundation–continues to work on treatments to improve the lives of those living with Progeria.
To that end, the Foundation recently announced the results of their 4th Progeria clinical trial – the triple drug trial – was published online by the journal Circulation. Building on the success of the lonafarnib monotherapy trial, investigators tested a combination therapy of lonafarnib, pravastatin and zoledronic acid in 37 Progeria patients.
The study found increased bone mineral density, but no other improvements (weight gain or cardiovascular variables) were noted beyond the earlier lonafarnib trial. No patients withdrew due to side effects.
That is the good news. The bad news is that it is not clear that the improvement is of clinical benefit. To that end, the researchers are using the data collected to begin a new clinical trial combining lonafarnib with everolimus.
In a news release, Sam Berns’ mother, Dr. Leslie Gordon, Medical Director of The Progeria Research Foundation said, “The results of the triple drug trial demonstrate the need for us to continue an aggressive study protocol as we search for additional treatments and a cure. It is vital to continue to identify treatments with the most promise to offer these children longer, healthier lives.” Dr Gordon added, “PRF continues to fund promising research and clinical trials aimed at curing Progeria. PRF is currently funding and co-coordinating a promising new two-drug trial to assess lonafarnib plus everolimus, at Boston Children’s Hospital Children are enrolling from the USA and countries throughout the world”
The reasoning behind the lonafarnib plus everolimus study is that lonafarnib may block progerin from developing, while everolimus appears to allow cells to more rapidly clear out the toxic progerin protein. Thus with everolimus targeting a different pathway than lonafarnib, the combination may prove to be a “one-two punch” to Progeria.
For more information about the clinical trials, click here.