Preclinical Research Shows Promise For New Approach to Treating Progeria


New research is shedding light on a possible new approach to treating the rare and fatal premature aging syndrome, progeria.

Progeria, also known as Hutchinson-Gilford progeria syndrome, is linked to progerin, a defect form of the lamin A protein found in the cell nucleus. The protein helps hold the nucleus together but the mutation inhibits cell division. It is believed that the defective protein makes the nucleus unstable, which could be what leads to the process of premature aging. Progerin is also found in healthy subjects and has been observed to increase with age, suggesting the results may also be important for normal aging and age-related disease.

The syndrome affects about one in 18 million children, which means there are less than 1,000 known cases in the world. That premature aging leads to early-onset death from cardiovascular issues in children at an average age of 14 to 15. Signs of progeria are usually seen within the first two years of life. They include growth failure, loss of body fat and hair, aged-looking skin, stiffness of joints, hip dislocation, generalized atherosclerosis, cardiovascular disease and stroke.

Researchers at Sweden's Karolinska Institute and IFOM, the FIRC Institute of Molecular Oncology in Italy have identified a new potential approach to treating this disease with antisense oligonucleotide therapies. Data from the study was published in the journal Nature Communications. The research team used cell samples from progeria patients to “show an impaired function in the telomeres, a compound structure at the end of chromosomes and the accumulation of “so-called telomeric non-coding RNA.” When the scientists added antisense oligonucleotides, they were able to reduce the level of telomeric non-coding RNA, which lead to normalized cell division. Antisense oligonucleotides are often used to inactivate harmful genes. It’s thought that the normalize cell division will improve the condition of the patients and possibly extend their lives.

Calling the work “promising,” Agustin Sola-Carvajal, the co-author of the study, said they saw positive results in gene-altered mouse models of progeria.  With the addition of the antisense oligonucleotides, the team saw a 44% increase in maximum life expectancy and a 24% increase in average life expectancy.

Maria Eriksson, a professor at Karolinska Institutet, said the effects have been positive in mice but they need to rethink ways to treat the disease in humans.

“More research is needed to assess how the relatively low levels of progerin seen in healthy individuals contribute to aging and age-related disease,” Eriksson said in a statement. “It is interesting to note that antisense oligonucleotides are now included as drugs in advanced clinical trials, some of which are already approved by the FDA in the U.S.”

A number of approaches have been made to develop therapies for progeria. California-based Eiger BioPharmaceuticals is expected to file a New Drug Application with the U.S. Food and Drug Administration by the end of the year for its lonafarnib therapeutic for progeria and progeroid laminopathies.

Lonafarnib, which has been granted Orphan Drug designation Breakthrough and Rare Pediatric Disease designation by the FDA, is a first-in-class, orally active inhibitor of farnesyltransferase, an enzyme involved in the modification of proteins through a process called prenylation.

The Salk Institute has also developed a new type of gene editing called SATI that could provide a treatment option for progeria, as well as other mutation diseases such as Huntington’s disease.

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