By Dr Ángeles Mencía

My name is Dr Ángeles Mencía, a researcher at CIEMAT in Madrid, where I have done extensive work in the field of epidermolysis bullosa (EB). My academic background includes research in human molecular genetics, and, during my postdoctoral years, I entered the field of molecular diagnosis of individuals with various forms of EB. This means providing genetic test results to people with EB symptoms to confirm the specific type of EB that they have. Simultaneously, I embarked on the path of gene editing-based therapeutic approaches, with a special focus on recessive dystrophic epidermolysis bullosa (RDEB). At present, my research team and I are steadily advancing in the in vivo treatment of diverse aspects of EB. In vivo treatments are applied to a person directly rather than to their cells in a laboratory (called in vitro).

 

Which aspect of EB are you most interested in?

My passion is deeply rooted in the search for new ways to correct the genetic changes that cause EB. The promising avenues unlocked by gene therapy have motivated us to advance further with this transformative approach. Viral vectors, our invaluable laboratory tools, have emerged as an essential method for correcting genetic changes or to deliver healthy genes to restore the proteins affected in EB. These vectors, often from diverse viruses (such as adenovirus or herpesvirus), offer us a pathway to the potential "cure" of genes in people with EB. As researchers, we aim to use advanced molecular tools to give patients correct diagnoses. Then, we'll try to find ways to reduce symptoms or even cure the disease starting from its genetic roots.

 

What difference will your work make to people living with EB?

Our research efforts are directed towards a topical "viral cream" with the potential to help heal all the skin blisters and wounds suffered by people with EB, leading to permanent healing of the treated areas. Although our research is still in its experimental stages, we have high expectations for this new viral vector based on the porcine (pig) pseudorabies virus (from the Herpesviridae family of viruses). It offers advantages over others, such as a natural ability to target skin cells, improved safety and easier large-scale production. Using this virus, we aim to generate treatments for RDEB that complement those currently in clinical trials, with the potential for longer lasting impact after they are applied.

 

Who/what inspired you to work on EB?

My journey in EB research began during my postdoctoral years, when I collaborated in the genetic testing of individuals with various types of EB. It was during this time that I had the opportunity to attend dermatology consultations with Dr. Raúl de Lucas at the Hospital La Paz to collect family genetic information. There, I had the chance to talk with families living with EB and I met people from the DEBRA Spain team. That human connection is what keeps us going in the lab every day, despite the challenges and frustrations of research, with the unwavering conviction that we are bringing a ray of hope to all those living with EB.

 

What does the funding from DEBRA mean to you?

This funding means the possibility of developing the production platform for this new viral vector and improving safety to generate a drug that can be applied to human skin. For me, it is a path to independence to pursue my vision in EB research.

 

What does a day in your life as an EB researcher look like?

When I arrive at the lab, the first thing I do is check emails and pending tasks. Then I meet with my group, usually over coffee, to discuss the results we have obtained and design the experiments to move forward. We review any new results published by other researchers in relation to different gene editing tools and viral vectors for in vivo delivery of these tools. Particularly those that are being carried out in EB, but also those in other conditions that could be transferable to the treatment of the skin.

After that, work at the laboratory bench carrying out experiments and, occasionally, writing up our results into manuscripts for publication or presentations at conferences and grant proposals occupies the rest of my day.

 

Who’s on your team and what do they do to support your EB research?

I started my research in EB with Dr Rodolfo Murillas, researcher at CIEMAT, and Dr Marta García, professor at the University Carlos III of Madrid. Rodolfo, my mentor, has been fundamental in my training as a researcher. Marta guided me through my early stages of EB research. Both bring extensive experience in the diagnosis, modelling and treatment of EB. Together, they help me create gene editing therapeutic tools, generate models for skin diseases to test new therapies on before they are progressed to clinical trials in humans, produce viral vectors and analyse skin samples under the microscope. Diana de Prado is the most recent addition to our team. As a PhD student, she is actively involved in the experimental work of producing and testing viral vectors, as well as in the experimental design and analysis of the results. Research on these therapeutic viruses for EB requires additional skills I am learning from Dr. Mirentxu Santos, a researcher at CIEMAT, who is an expert in EB models. A key collaborator in this project is Dr. Silvia Gómez, a professor at the Autonomous University of Madrid. She specializes in herpesvirus vectors, specifically the porcine pseudorabies virus that is the focus of this research project and its use in gene therapy.

 

How do you relax when you’re not working on EB?

When I finish my day in the lab, it's time to be with my family, share a nice dinner with my husband and kids, and talk about how the day went. Another hobby of mine is belly dancing. I participate in a semi-professional group and we perform once or twice a year.

 

What these words mean:

Molecular genetics = the study of DNA molecules as opposed to population genetics which looks more at evolutionary changes within groups of plants or animals.

Molecular diagnosis = identifying the specific DNA change causing a person’s EB symptoms.

Gene editing = a type of gene therapy where a person’s own gene is altered to correct a change that is responsible for a condition.

In vivo treatment = treating a person’s body directly as opposed to in vitro treatments which take cells from a person’s body and treat them in a laboratory before returning them to the patient.

Models/modelling = ways of testing therapies before trialling them on actual people in a clinic.

Manuscript = a written explanation of a researcher’s experiment that will be published so that other researchers can see what was done and the results that were achieved.

Viral vectors = altered viruses that safely deliver new genes into cells. Viral vectors overview: https://youtu.be/Q6qk6Wh6cXU

 

Full glossary of scientific terms