SKIN LIKE BUTTERFLY WINGS: UP scientists investigate rare deadly disease

By Eunice Jean Patron, UPD-CS SciComm

As rare and deadly as it is poetically named, “Butterfly’s Disease” (scientifically known as “epidemolysis bullosa” or simply “EB”) has no known cure. But a handful of Filipino scientists are working their way towards a treatment.

EB is a very serious disease, for those afflicted as well as for their families. Sufferers have severely fragile skin that easily blisters and tears even with the slightest touch, hence the comparison to butterfly wings. EB also varies in form, with mild cases that only affect the outer skin to extreme cases that injure even internal organs—an extreme condition that can lead to severe disability or even death.

To further understand Butterfly’s Disease, scientists from the University of the Philippines – Diliman College of Science (UPD-CS) have focused on a genetic mutation known to cause an even rarer type of EB called Junctional EB (JEB), which affects more layers of the skin and can be fatal if it happens during early infancy.

Genetic investigators’ surprise discovery

The onset of JEB has been associated with a genetic mutation called G273D that affects how the body produces a protein called ITGA6-ITGB4 integrin (or Integrin A6B4 for short), which plays a vital role in joining together cells and tissues. The G237D mutation causes the production of malfunctioning Integrin A6B4 and decreases the presence of functional Integrin A6B4 on epithelial cell surfaces, leading to weaker cell adhesion in the skin tissue and resulting in severe skin blisters.

Molecular biologist Dr. Neil Andrew Bascos and his graduate students, Kim Ivan Abesamis and Camille Anne Bagoyo, of the National Institute of Molecular Biology and Biotechnology (UPD-CS NIMBB) are investigating just how G237D affects the structure of Integrin A6B4.

“We weren’t looking to study EB when we started this study,” Dr. Bascos narrated. “The main goal of the research has previously been looking at the function of integrins and their roles in cancer. Interestingly though, we’ve found that integrins may be associated with many other relevant diseases.  Finding its involvement in this disfiguring disease provides us a means through which our research may be able to help the afflicted people.”

In their computational study, the researchers investigated how the G237D mutation prevents Integrin A6B4 from forming, and from  binding their targets properly.  Some factors, such as the presence of calcium ions, were also observed to stabilize integrin interactions.

Paving the way for future research

The study sets the direction for further research into factors that can alter the effect of the G237D mutation on Integrin A6B4 function. Exploring these factors can pave the way for discovering cures for EB. “At this point, it’s very much basic research, medyo predictive pa. It would need proof of principle, but these studies give us concrete targets to test in the search for ways to alleviate the disease,” Dr. Bascos said.

Some people with EB die as infants. Others manage to survive, but suffer from chronic illnesses that stem from its effects.  Although little is currently known about effective treatments and cures for Butterfly’s Disease, the UP scientists remain steadfast in their quest to gain a deeper understanding of EB, in hopes of improving the quality of life of these patients and their families.

References:

Abesamis, K. I. A., Bagoyo, C. A. S., & Bascos, N. A. D. (2021). Investigating the effect of a non-conservative mutation (G273D) on integrin alpha6-beta4 binding interactions. Biophysical Journal, 120(3). https://doi.org/10.1016/j.bpj.2020.11.1709

Cincinnati Children’s Hospital Medical Center. (n.d.). Epidermolysis Bullosa. Retrieved from https://www.cincinnatichildrens.org/health/e/epidermolysis-bullosa

EB Research Network. (n.d.). Understanding EB & its classification. Retrieved from https://www.eb-researchnetwork.org/research/what-is-eb/

GMA Integrated News and Public Affairs. (n.d.). Butterfly Child. Brigada. Retrieved from https://www.facebook.com/watch/?v=1693026984165308.