Hutchinson-Gilford progeria syndrome is a genetic condition characterized by the dramatic, rapid, appearance of aging from the childhood. Hutchinson-Gilford progeria syndrome is caused by a mutation in the lamin A (LMNA) gene. The affected children develop a characteristic facial experience including prominent eyes, small chin, protruding ears, thin lips and a thin nose with a beaked tip. This syndrome also causes hair loss (alopecia), joint abnormalities, aged-looking skin, and a loss of fat under the skin (subcutaneous fat). Moreover, patients of Hutchinson-Gilford progeria syndrome experiences severe hardening of the arteries (arteriosclerosis) from the childhood. The condition worsens with age and increases the risk of heart attack or stroke even at a young age.
Hutchinson-Gilford progeria is a rare condition that affects about one in four million newborns worldwide according to the National Institutes of Health (NIH). Until now more than 130 cases have been reported as per the NIH statistics. The affected patients live up to 30 years maximum, with an average life span of 13 years. Nearly 90% of the patients die from complications related to atherosclerosis. Till 2012 there wasn’t any effective treatment therapy discovered for Hutchinson-Gilford progeria syndrome. The treatments available focused mostly on reducing cardiovascular symptoms and growth abnormalities.
Farnesyltransferase Inhibitor (FTI)
In 2012, findings of the first clinical trial of the drug Lonafarnib, a farnesyltransferase inhibitor (FTI), gave a new hope for the treatment of children with Hutchinson-Gilford progeria syndrome. Clinical trial results demonstrated improvement in weight gain, increase in bone mineral density, reduced vascular stiffness, and improved sensorineural hearing in patients with progeria. Previous treatments with growth hormone, and Sulforaphane helped in reducing the symptoms, and prolong a child’s life. However, it is essential that the patient regularly visits the cardiologist. Rapamycin is one other drug used before, that demonstrated to reverse nuclear blebbing, retard cellular senescence, and facilitate degradation of progerin.
Recently in 2015, the scientists at the Agency for Science, Technology & Research (A*STAR) successfully established a model of Hutchinson-Gilford progeria syndrome. The study conducted by this organization proposed a model which implies that progerin is linked to telomeres. Progerin induces a reduction in heterochromatin, a tightly packed form of DNA, making telomeres in the cell more fragile and susceptible to damage. The damaged telomeres in turn trigger premature cellular aging. This model is radically different from the one believed earlier – the gene progerin caused the nucleus to be deformed, thereby weakening the ability of cells to divide and proliferate. The altered progerin protein makes the nuclear envelope unstable and progressively damages the nucleus, making cells more likely to die prematurely.
Researchers are working to determine how genetic changes further leading to the characteristic features of Hutchinson-Gilford progeria syndrome. Continuous advancement in research with increased understanding of the human aging will provide valuable insights and aid in the treatment of this disease.
Research and development activities by major institutes to find novel therapies for age-related conditions is expected to offer lucrative opportunities for market players. For instance, in August 2019, researchers from the Houston Methodist Research Institute at the Texas Medical Center are focused on using RNA therapeutics—treatment that is focused on ribonucleic acids, a substance found in all living cells—to slow, and possibly reverse Hutchinson-Gilford Progeria.
Similarly, in July 2019, researchers from the University of Oviedo in Spain found that fecal microbiota transplants can help prematurely old mice live longer. The research may help to design targeted probiotic treatments for age-related conditions such as Hutchinson-Gilford Progeria in humans.
Moreover, in March 2019, researchers at the Centro Nacional de Investigaciones Cardiovasculares (CNIC) and the Universidad de Oviedo identified a new molecular mechanism involved in the premature development of atherosclerosis in mice with Hutchinson-Gilford progeria syndrome. The newly identified therapeutic target can be used for blocking early atherosclerosis in progeria.