According to the National Center for Advancing Translational Sciences, there are about 7,000 rare diseases that affect 25-30 million individuals in the United States. Of those 7,000 rare diseases, fewer than 10% have an effective treatment. From 1973 to 1983, fewer than ten treatments for rare diseases were approved by the Food and Drug Administration (FDA). This led to the passage of the Orphan Drug Act of 1983, an act that established financial incentives to develop treatments for rare diseases. Since then, the act has led to many breakthroughs.
One such breakthrough occurred on November 20, 2020, when the FDA approved Zokinvy™ (lonafarnib). Zokinvy is the first and only available treatment for Hutchinson-Gilford progeria syndrome (HGPS) and two other genetic diseases, classified as “processing-deficient Progeroid Laminopathies“, which all cause premature aging and death. Without treatment, individuals with HPGS die at an average age of 14.5 years from heart failure, heart attack, or stroke resulting from severe hardening of the arteries. Because of the work of numerous scientists, doctors now have a better understanding of the extremely rare HGPS and two other processing-deficient Progeroid Laminopathies. With these findings, researchers were then able to discover a drug, Zokinvy, that targets the underlying mechanism of premature aging in these rare genetic diseases.
Image Source: LUIS ROBAYO
Zokinvy works by being a “farnesyltransferase inhibitor”, which means that it reduces the amount of farnesyltransferase activity. Farnesyltransferase is a molecule that typically carries out the addition of a farnesyl group to specific proteins. Genetic mutations that cause HGPS and the processing-deficient Progeroid Laminopathies form defective progerin and progerin-like proteins, respectively. An essential step in the formation and accumulation of these progerin and progerin-like proteins is the addition of farnesyl by farnesyltransferase. Therefore, inhibiting farnesyltransferase actually reduces the build-up of defective progerin and progerin-like proteins in the nucleus of the cell.
Unfortunately, Zokinvy is not a cure, but rather it is a treatment that offers a more prolonged life for these individuals. Researchers believe that Zokinvy works by slowing the build-up of defective progerin and progerin-like proteins, but over time this continued build-up still leads to instability of the nucleus, subsequent damage of tissue in the human body, and the process of premature aging.
Overall, the Zokinvy clinical trials were promising, showing improved cardiovascular health and an increased average lifespan of 2.5 years for individuals with HGPS. Furthermore, Zokinvy is a hopeful sign for the future development of better treatments and potential cures for both HGPS and processing-deficient Progeroid Laminopathies. Lastly, with continued research and a more complete understanding of these premature aging disorders, researchers may also have an additional model for studies into the normal aging process.
Featured Image Credit: Jorge C. Lucero
