Scientists at the University of Bath, King’s College London and Brunel University London, UK, have created a molecule offering protection to patients with rare genetic disease.
According to new research skin cells taken from patients with a rare genetic disease are up to ten times more sensitive to damage from ultraviolet A (AVA) radiation in laboratory tests, than those from a healthy population. The scientists have custom-built a molecule which acts like a claw to scoop up excess iron particles within mitochondria, preventing them from amplifying UVA-induced damage. The goal is to essentially see this molecule added to sun creams to enhance their protective effect against UVA rays.
Tackling the rare genetic diseases that come from UVA damage
Although most sun creams are effective against UVB rays, generally they only protect against UVA rays through the reflective properties of the cream alone. When cells are exposed to UVA rays, the damage caused to cells can be aggravated by excess free iron in mitochondria which fuels the generation of ‘free radicals’, including Reactive Oxygen Species (ROS), which can damage DNA, protein and fats – increasing the risk of cell death and cancer.
It is hoped that the work, which has involved designing a brand-new molecule with potential to be added to sun cream, could benefit those with the rare genetic disease Friedrich’s Ataxia (FA), as well as those with other disorders characterised by mitochondrial iron overload, notably Wolfram Syndrome and Parkinson’s disease, where UVA rays from the sun may pose particular challenges.
Patients with FA have high levels of free iron in their mitochondria. This new research, led by scientists at the University of Bath, King’s College London and Brunel University London shows that this excess free iron makes skin cells from these patients up to 10 times more susceptible to UVA damage.
Build-a-molecule
In a series of in vitro experiments using human skin cells called fibroblasts from FA patients, the researchers demonstrated that their claw – termed an ‘iron chelator’ – decreased damage to mitochondria membranes from realistic doses of UVA rays by a factor of two.
In cells pre-treated with the chelator, UVA-mediated cell death was prevented. The chelator is cleverly designed so that it travels to the mitochondria specifically.
Dr Charareh Pourzand, from the Department of Pharmacy and Pharmacology at the University of Bath, explained: “Unfortunately, because mitochondria are so crucial as the main source of energy, when something goes wrong with them, the consequences can be severe. Mitochondria dysfunction lies at the heart of a growing number of diseases.
“Friedreich’s Ataxia is one example of a disease of ‘mitochondrial iron overload’. Our results -should they translate to people’s skin (in vivo), suggest that patients could be up to 10 times more sensitive to UVA. The damage you and I would get in our skin from for example 2.5 hours’ exposure to solar UVA would be 4-10 times higher for a patient with FRDA.
“There’s a vicious cycle – excess iron in the mitochondria means more reactive oxidising species and more damage to cell constituents, resulting in cell functions being compromised. This situation leaves cells more sensitive to subsequent oxidative damage notably by environmental factors such as UVA of sunlight.
“We’re interested in the biology of iron and how it impacts humans and disease. One of our goals is ultimately to develop new therapies to protect from the sun. Our research shows that adding an iron chelator to sun creams could enhance the photoprotective capability of current preparations and be particularly beneficial to people with acute sensitivity to solar UVA.
“We hope that our findings can be ultimately translated to the people to give them a better quality of life, and that we can inspire other researchers to follow those avenues. We are very thankful to our sponsor the Biotechnology and Biological Sciences Research Council (BBSRC) to have made this project feasible.”
