Nanoneedle wound study in RDEB

Some RDEB wounds can develop into skin cancer (SCC). This PhD studentship will train a new EB researcher while developing a painless tool to take samples that could aid choice of the best dressings to help wounds heal and avoid unnecessary biopsies.

Prof John McGrath works at King’s College, London, UK on this project to study wounds in RDEB by taking tiny samples across a wound surface using patches of nanoneedles. Nanoneedles are hundreds of thousands of times smaller than the needle that would be used to take a blood sample, over a thousand times thinner than a human hair, and tiny enough that they can pierce a single cell. The molecules found in these nanoneedle biopsies will be studied to better understand whether cancer is developing and what dressings will help an individual wound to heal.

About our funding:

Research leader	Prof John McGrath
Institution	St John's Institute of Dermatology, King's College London, UK
Type of EB	RDEB
Patient involvement	Nanobiopsies taken during routine clinical care
Funding amount	£142,035 (co-funded with Mölnlycke)
Project length	PhD studentship: 3 years
Start date	1 September 2022
DEBRA internal ID	McGrath22

Latest progress summary (2023):

Researchers are addressing three aims: 1 - to detect RDEB cancer without biopsies, 2 – to be able to test whether wounds are likely to heal or not so the most appropriate dressings can be used, and 3- to deliver gene therapy using tiny nanoneedles to help RDEB wounds heal.

Biopsy samples from the edge of an RDEB tumour and unaffected RDEB skin have been used to compare different ways of detecting cancer. A technology called ‘Raman microscopy’, that hasn’t been used before on skin, has been developed to detect RDEB skin cancer in the biopsies. This could potentially be used, without a biopsy, by shining light directly onto the skin at the bedside. Comparing this to regular microscopy and an additional technology using nanoneedle sampling will show how accurate each technology is at picking up early stages of cancer and wound healing.

Cells from the biopsies have also been treated with gene therapy using nanoneedles to fix the genetic mistake responsible for RDEB symptoms. This shows promise for treating skin directly via dressings containing nanoneedle patches in the future.

About our researchers:

Lead researcher: John McGrath MD FRCP FmedSci is Professor of Molecular Dermatology at King’s College London and Head of the Genetic Skin Disease Unit, as well as Honorary Consultant Dermatologist at St John’s Institute of Dermatology, the Guy’s and St Thomas’ NHS Foundation Trust in London. He was previously a DEBRA-funded junior EB research fellow and has worked on EB research for more than 25 years. He now leads and collaborates on several national and international projects to develop gene, cell, protein and drug therapies that can lead to better treatments for people living with EB.

Co-researchers: Dr Ciro Chiappini, Dr Mads Bergholt, Prof Jemima Mellerio

Collaboration: Mölnlycke Health Care

Why this research is important:

Our project hopes to develop a new bedside tool which can use painless nanoneedle sampling to generate nanobiopsy material which can then be evaluated to generate data which give a better indication of whether SCC is present and whether a skin biopsy is needed or not. Thus, developing a bedside diagnostic tool will improve how EB healthcare teams evaluate and monitor wounds in people with RDEB.

The second goal is to be able to generate molecular data about wounds and how these are impacted by the application of certain dressings… Ultimately, we hope to be able to use this information to help EB healthcare teams and people with EB choose and apply the best dressings to help their wounds heal.

John McGrath

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Researcher's abstract:

Grant title: Improved characterization of chronic wounds in RDEB

This project offers a new approach to assessing wounds and wound healing interventions in the inherited blistering skin disease, recessive dystrophic epidermolysis bullosa (RDEB).

Ultimately, we wish to develop a bedside test to inform on whether a wound is healing or not, whether a biopsy is indicated (e.g., for cancer), or what might be the best dressing to apply to the wound to promote optimal wound healing.

Using technologies and methods unique to the investigators, we aim to use nanoneedle tissue sampling to develop molecular micro-profiling of RDEB wounds. The work will involve Raman Spectroscopy Imaging and Mass Spectrometry Imaging of nanobiopsy material aligned to machine learning classification algorithms.

Initially, we plan to work on RDEB wound skin biopsies (taken as part of routine clinical care) to match the molecular profiles to skin histology. The work will then expand to in vivo sampling from patients to develop a more dynamic readout of the status of an RDEB wound. The goal is then to begin to use the technology to assess the impact of various wound care dressings on wound healing. Ultimately, the approach could lead to a more evidence-based approach to dressing selection for specific wounds in individual patients.

Researcher’s progress update:

Updated grant title: Improving wound healing monitoring and treatment options for patients with recessive dystrophic epidermolysis bullosa.

This project is about wound healing in RDEB. We want to address three main challenges. First, we want to develop a new way of detecting cancers in RDEB wounds at an early stage without having to resort to taking multiple skin samples. Secondly, we want to develop new readouts of the state of wound healing (likely to heal or not) which will provide guidance on which dressing might be the best one to apply to the wound. Thirdly, we want to try to improve wound healing in RDEB by correcting the COL7A1 gene by gene editing, delivering the correction using tiny needles called nanoneedles. At this stage, we are mainly focusing on the first challenge. We are testing a technology called “Raman microscopy” which is something new for the skin. This approach bounces light off the skin and then, depending on what the light hits, we can detect the rebounding light which comes back at different wavelengths. The readouts of the various wavelengths look different for proteins, fats, and other components of skin. Our work is showing that RDEB skin cancer can be picked up by Raman microscopy. With further refinement, we plan to test how good this approach will be at picking up early cancer. If successful, in the future we would like to develop a device to use in the clinic for screening for cancer without having to take a skin biopsy. As the project develops, we will also address the issue of choice of best dressing along with another technique for assessing the state of wounds called mass spectroscopy which can give additional information about wound healing. We are also making progress in gene editing skin cells from people with RDEB using the nanoneedles. The next step will be to study the impact of the gene repair in models of RDEB before we can make plans for clinical trials and hopefully the journey to a new treatment that can make RDEB wounds heal better. (From 2023 progress report.)