New Research Projects 2019
Professor Alain Hovnanian, Head of the research laboratory on genetic skin disease at Imagine Institute, Paris
Professor Fernando Larcher, Universidad Carlos 3 Madrid
Professor John McGrath, Professor of Molecular Dermatology at Guy’s and St Thomas’ NHS Foundation Trust, Kings College London
This is a clinical trial which aims at using gene corrected grafts to treat chronic wounds of patients with RDEB.
A skin biopsy is taken from the EB patient, which is used to culture cells called keratinocytes and fibroblasts in the laboratory. These are then converted with a viral vector which contains a copy of the COL7AI gene which is faulty in Recessive Dystrophic EB patients. These gene corrected cells are used to produce a full-thickness graft called a skin equivalent, which will be grafted onto chronic wounds
As the grafts are gene corrected in all layers, they have the potential to permanently heal the areas they are grafted on to.
The preclinical work for EBGRAFT was made possible through a European Research Grant project called Genegraft – click here to learn more. Cure EB is funding the first phase 1/2 clinical trial.
Constant Pharmaceuticals – Clinical Development of TXA127
Cure EB has joined a consortium with three other EB charities to fund the development of an anti-fibrotic drug called TXA127.
Part of this work will be done in the laboratory of Dr Thomas Walther at University College Cork, who is developing a blood assay for the drug, which hopes to reduce the formation of mitten deformities in the hands of RDEB patients.
In the first part of the program, Constant Pharmaceuticals will develop an oral formulation of the drug, as its current form as a subcutaneous injection is not suitable for EB patients.
The second part of the program will be a Phase 2 clinical trial in Europe and the USA.
Research summary infographic – click to see full-sized version
Mesenchymal Stromal Cells (Msc’s)
MSC’s are cells isolated from umbilical cord blood, bone marrow and other sources. Sometimes called stem cells, they can measure into different cell types and are able to stimulate anti inflammatory responses. Inflammation is considered a key factor in some of the complications that arise in Recessive Dystrophic Epidermolysis Bullosa (RDEB) such as poor wound healing, itching pain and importantly the particularly aggressive malignant skin cancer that develops.
DEFINITION: Gene editing (or genome editing) is the insertion, deletion or replacement of DNA at a specific site in the genome of an organism or cell. It is usually achieved in the lab using engineered nucleases also known as molecular scissors. This work will not just benefit EB but will in theory be applicable to the people who suffer one of the estimated 5400 genetic disorders in the world, which accounts for 10% of people, 30 million in Europe alone.
Therapeutic Reprogramming Consortium
- Continuation of gene editing projects in the UK and US with a focus on getting to clinical trials both locally and whole body
- Continuation of gene modified stem cell work aiming for clinical trials if preclinical research is supportive
- Continuation of funding towards mesenchymal stromal cell production at Kings College London and treatments at Great Ormond Street Hospital
- Generation of gene modified skin grafts and clinical trial
- RNA project
- RDEB squamous cell carcinoma is a particularly aggressive malignant skin cancer. It has extremely high mortality and young adults with severe RDEB are at huge risk of developing it. We aim to pursue projects researching treatment options
- Gene modification and gene editing approaches for Junctional EB
- New project exploring novel treatment approaches for both local and systemic treatments including delivery mechanisms, skin substitutes and protein therapy
- Dedicated GMP facilities for gene editing, gene modification and EB gene and cell therapy treatment suite
- Lectureships in Dermatology, PhD studentships and Clinical Research fellowships