Progeria and Atherosclerosis
Progeria, also known as Hutchinson-Gilford progeria syndrome (HGPS), is a rare disease affecting just 400 people across the world. It is caused by a mutated LMNA gene. This mutation makes the nucleus of cells unstable, leading to premature aging. Patients have a high risk for developing cardiovascular disease and often suffer from heart attacks or strokes. Additional symptoms include joint abnormalities, hair loss, a scleroderma-like skin condition, and fat loss. Sadly, the condition is currently fatal with most patients dying between the ages of 6 and 20.
Atherosclerosis is caused by a buildup of immune cells and cholesterol in the blood cells, restricting blood flow. When these blockages caused by atherosclerosis rupture, strokes or heart attacks can occur. The main cause of atherosclerosis is aging, meaning children with progeria are very susceptible to the condition. In fact, this prognosis can be worse for progeria patients because these individuals typically have arteries with multiple defects already.
New Findings
The Centro Nacional de Investigaciones Cardiovasculares (CNIC), in collaboration with the Universidad de Oviedo, have recently made two noteworthy contributions to the study of atherosclerosis in progeria.
First, they uncovered a new molecular mechanism which is involved in the appearance of the condition in HGPS patients. Second, they believe they have found a new potential therapeutic target for atherosclerosis which could slow its progression. This could ultimately extend the lifespan of progeria patients.
The results from this research have been published in the EMBO Molecular Medicine journal.
The Study
Research of atherosclerosis in progeria has been, like all rare diseases, limited by the number of patients living with the condition. Even more restraining is the fact that researchers hadn’t yet developed an animal model who had atherosclerosis and progeria.
These researchers thankfully were able to generate the very first mouse model which encompassed both of these conditions. It is this model which allowed them to finally uncover these noteworthy results.
What they found is that unfolded protein response (UPR) caused by endoplasmic reticulum (ER) stress contributes to the death of vascular smooth cells. This means that if researchers can find a therapy which targets this molecular pathway, they may be able to slow vascular disease progression in progeria patients.
Thankfully, these researchers did.
They investigated a compound called tauroursodeoxycholic acid, otherwise known as TUDCA, in the mice. It effectively reduced the effects placed on the vascular smooth cells. That means that TUDCA could become an effective way to inhibit the progression of atherosclerosis and vascular disease in those living with HGPS. Ultimately, these new discoveries could lengthen the lifespan of this patient population.
You can read more about this study and the outcomes it could have for progeria patients here.
