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We’re thrilled to share the results from two very exciting breakthrough studies on the use of RNA therapeutics in Progeria research.  Both studies were co-funded by The Progeria Research Foundation (PRF) and co-authored by PRF’s Medical Director, Dr. Leslie Gordon.

Progerin is the disease-causing protein in Progeria. The RNA therapies interfere with the body’s ability to produce progerin, by blocking its production at the RNA level.  This means that the treatment is more specific than most therapies that target progerin at the protein level.

Though each study used a different drug delivery system, both studies targeted the same basic treatment strategy, inhibiting production of RNA coding for the abnormal protein, progerin. Both were led by researchers at the National Institutes of Health (NIH), and were published today in the journal Nature Medicine.

One study, led by Francis Collins, MD, PhD, Director of the NIH, showed that treating Progeria mice with a drug named SRP2001 reduced the harmful progerin mRNA and protein expression in the aorta, the main artery in the body, as well as in other tissues. At the end of the study, the aortic wall remained stronger and the mice demonstrated an increased survival of over 60%.

“To have a targeted RNA-therapy show such significant results in an animal model gives me hope that this could lead to a major advance for the treatment of progeria,” said Collins.

The other study, led by Tom Misteli, PhD, Director of the Center for Cancer Research, National Cancer Institute, NIH, showed a 90 – 95% reduction of the toxic progerin-producing RNA in different tissues after treatment with a drug called LB143. Misteli’s lab found that progerin protein reduction was most effective in the liver, with additional improvements in the heart and aorta.

We now know there are multiple ways to decrease production of the harmful progerin protein using RNA therapeutics. Each study found different stretches of RNA in the mouse models that, when targeted, delivered an effective pathway for treatment, resulting in Progeria mice that lived much longer than those treated in previous studies with Zokinvy (lonafarnib), the only FDA approved drug for children with Progeria. Furthermore, researchers found that a combination treatment with RNA therapeutics and Zokinvy (lonafarnib) reduced progerin protein levels in liver and heart more effectively than either single treatment on its own.

“These two highly important studies demonstrate the major advancements that are now upon us in the field of targeted Progeria therapeutics,” said PRF Medical Director, Dr. Leslie Gordon. “I was thrilled to work with these brilliant research groups to advance RNA therapy for children with Progeria. Both are exciting proof-of-principle studies, and PRF is excited to forge ahead towards clinical trials that apply these treatment strategies.

 

Erdos, M.R., Cabral, W.A., Tavarez, U.L. et al. A targeted antisense therapeutic approach for Hutchinson–Gilford progeria syndrome. Nat Med (2021). https://doi.org/10.1038/s41591-021-01274-0

Puttaraju, M., Jackson, M., Klein, S. et al. Systematic screening identifies therapeutic antisense oligonucleotides for Hutchinson–Gilford progeria syndrome. Nat Med (2021). https://doi.org/10.1038/s41591-021-01262-4