Treating JEB with laminin protein

Putting back the protein that is missing from JEB skin could prevent skin blistering and improve wound healing.

Dr Matthew Caley works at Queen Mary University, London, UK on this project to see if commercially available laminin protein can be delivered into JEB skin and restore it to health. JEB symptoms are caused when changes to the genetic recipe for laminin means a person can no longer make enough of their own laminin protein. This work aims to discover if it is possible to replace the protein by injecting it into healthy skin or using it in a gel treatment on blistered skin and, if so, whether this treatment can strengthen JEB skin and prevent blistering.

About our funding:

Research leader	Dr Matthew Caley
Institution	Queen Mary University London (QMUL), UK
Type of EB	JEB
Patient involvement	None
Funding amount	£177,304.39 co-funded with DEBRA Ireland
Project length	2 years
Start date	3 June 2024
DEBRA internal ID	GR000027

Latest progress summary:

Due 2025.

About our researchers:

Lead researcher:

Dr Matthew Caley is a Senior Lecturer in Cell Biology (Blizard Institute) with more than a decade of experience in skin research, matrix biology and generating in vitro skin models. He is currently running pre-clinical trials focused on a range of different skin diseases including JEB.

Co-researchers:

Dr Emanuel Rognoni is a Senior Lecturer at the Blizard Institute, QMUL. During his PhD he focused on the KEB subtype where he revealed a novel function of the integrin binding protein Kindlin-1 for epithelial stem cell homeostasis. He further specialized in skin research, investigating how different dermal fibroblast subpopulations organize and influence each other during development and wound healing in Prof Fiona Watt’s lab (KCL). Using genome-wide sequencing technologies, innovative 2D/3D culture platforms and skin transgenic/disease models, his group is now uncovering the molecular mechanisms and implications of fibroblast heterogeneity in skin health and disease.

Collaborators: BioLamina.

Back to contents

Why this research is important:

Our approach has the potential to treat blisters quickly and restore skin health, improving the quality of live and survival especially of younger patients, where other treatments are not feasible.

Dr Matthew Caley

Researcher’s abstract:

Grant title: Treating JEB With Recombinant Laminin 332

There is no cure for JEB, management of the disease focuses on managing the blisters, controlling infections and preventing complications. At the root of the disease is the loss of the protein laminin-332 from the skin. If we can restore laminin-332 we can accelerate wound healing and restore a healthier skin in JEB patients improving their survival. Our data show that supplementing synthetic laminin-332 has the potential to ameliorate JEB disease symptoms. This project focuses on identifying the best methods to deliver laminin-332 into the skin of JEB patients for efficient repair. Using our unique preclinical JEB model we will test different delivery methods, injections that would benefit unblistered but easily damaged skin and a topical gel that will benefit blistered skin. We will generate data showing how widespread our laminin restoration is, how long it lasts and demonstrating the effect on skin structure and wound healing. For this project we are closely collaborating with the Swedish company BioLamina who is specialised in the production of laminins for scientific and clinical use. If our preclinical tests are successful this unique partnership will allow us to move this work forward quickly into patient. Supplementing synthetic laminin-332 may not be a curative treatment, however, our approach has the potential to treat blisters quickly and restore skin health, improving the quality of live and survival especially of younger patients, where other treatments are not feasible.

Junctional epidermolysis bullosa (JEB) is a rare genetic skin disease leading to widespread blistering and impaired wound healing ability of the skin, our most important protective barrier. This is caused by the loss of vital proteins that anchor the outer layer of the skin to the rest of the body. The most severe form, JEB severe, is caused by complete loss of one of the parts of laminin-332 a key component of that anchoring structure. Babies diagnosed with this form of JEB nearly all die before their second birthday because of their malfunctioning skin. Patients with JEB have poor wound healing and they develop thick excess wound tissue in existing wounds that fail to heal, increasing the risk of blood poisoning (sepsis). Due to the extent of the wounds this severe subtype of EB is extremely painful. So far there are no effective treatments to halt or cure this deadly skin disease. In collaboration with BioLamina we propose to test if a synthetic laminin (produced by BioLamina) is able to improve wound healing and prevent skin blistering in our model of JEB. We will test different ways to deliver laminin into the skin (Aim-1), determine how long it remains in the skin (Aim-2) and if it improves skin strength (Aim-3) and wound healing (Aim-4). Our goal is to improve the skin of JEB patients, improve wound healing and therefore reduce the risk of infections that can lead to sepsis and premature death.

Researcher’s progress update: