History of EB research

EB Research is carried out by dermatologists and scientists who are pioneering techniques with EB that are applicable to many other conditions.

There is a huge unmet clinical need for effective treatments for this devastating condition and research is now on the brink of delivering some.

Incurable genetic diseases

There are about 6000 human genetic diseases and in principle, the mutation cause of the majority of them could be correctable by genome editing and other forms of gene therapy. This is approximately 10% of people, 30 million in Europe alone. With advancing technologies, the new medical miracle will be treatments for these ‘incurable’ conditions.

Scientific advances relevant to EB research

• EB first described by Austrian dermatologist Ferdinand Ritter von Hebra.

• EB-associated cancer first identified.

• Transmission Electron Microscopy (TEM) allowed differentiation of EB into three main categories.

• TEM shows abnormalities in keratin filaments in EBS, in hemidesmosomes in JEB, and anchoring fibrils in DEB.

• Antigen mapping brought the ability to diagnose and differentiate types of EB.

1991

• First EB genes (K5 and K14, and COL7A1) discovered and linked to EBS and DEB respectively.

1995

• First DNA based pre-natal diagnosis of RDEB carried out.

1997

• Revertant mosaicism in EB first described. (Jonkman et al.)

1999

• First COL7A1 knockout mouse exhibiting a severe phenotype generated in the US.
• By the late 1990s, 10 EB causative genes have been identified.

2000

• Grafting engineered human skin heals skin in animal (mouse & dog) models of RDEB.

2006

• First ex vivo gene therapy for a JEB patient performed (Mavilio et al.)
• Shinya Yamanaka discovered he could reprogramme mature cells to become pluripotent stem cells, i.e. immature cells that are able to develop into all types of cells in the body. He won a Nobel prize in 2012 for this discovery. Exciting research for EB around this work is ongoing.

2007

• Kindler Syndrome included as a fourth type of EB.
• John E. Wagner, a respected and experienced transplant surgeon, performed a bone marrow transplant on Nate Liao (who suffers from RDEB). This treatment yielded positive results and led to full bone marrow transplants in other children.

The results of this trial, whilst positive, highlighted the significant risks associated with full bone marrow transplants in RDEB patients. Two of the 7 children transplanted died. One as a result of pre-transplant treatment and the second because of transplant rejection 6 months after transplant. Treatment protocols have been changed but still carry a high risk.

2008

• A surviving RDEB mouse model developed in Germany.

2010

• The first ex vivo gene therapy study for RDEB started in the US (Marinkovich, Abeona Therapeutics).

2011

• First induced pluripotent stem cell (iPSc) from EB cells produced (read more: Tolar et al. and Itoh et al.)
• Katsuto Tamai and John McGrath identified, for EB, which cells in the bone marrow are important in repairing wounds in skin and also pinpointing the signalling mechanism that directs cells to the wounded areas marked a huge step in this direction.

2013

• First clinical trial of allogeneic fibroblast injections in 11 RDEB patients performed in the UK.
• Clinical diagnosis by next generation sequencing started.

2015

• 10 children with RDEB treated with autologous mesenchymal stromal cells (MSCs) in a clinical trial in the UK, funded by Cure EB (formerly the Sohana Research Fund).
• Gene editing a cure for leukaemia – Professor Waseem Qasim (UCL) used gene editing to disable a gene in donor cells that makes a receptor that recognises other cells as foreign. Read the New Scientist report.

2016

• First CRISPR correction of RDEB cells demonstrated.
• Targeted exon skipping restores type VII collagen expression and anchoring fibril formation in an in vivo RDEB model.

2017

• Lifesaving ex vivo gene therapy carried out on a seven-year-old boy with JEB in Europe. Read more or watch the video below.

• In vivo and ex vivo RNA trans-splicing correction of RDEB first demonstrated in mouse models.

2018

• Phase 2/3 trial of diacerein ointment in 17 EBS patients.
• Genetic landscape of RDEB tumours assessed
• European phase 1/2 clinical trial of losartan as an antifibrotic drug for children with RDEB commences.
• International phase 2 trial of rigosertib for RDEB-associated cancer initiated.
• Phase 2 study of topical delivery of the COL7A1 gene to RDEB patients usuing Herpes Simplex virus commenced.
• The first ex vivo gene therapy study for JEB patients with mutations in the COL7A1 gene started in Europe.

2019

• First clinical trial on exon skipping in RDEB started in Europe (Wings Therapeutics).
• First protein therapy for RDEB patients started. Phase 1/2 study with intravenous injection of collagen VII protein (Phoenix Tissue Repair).
• Results published of the first UK gene therapy trial in 4 RDEB patients being injected with gene corrected fibroblasts, a study funded by Cure EB.

2021

• The first large scale stem cell clinical trial in children with EB commences in the UK. Mission EB is part funded by Cure EB.

2022

• The European Commission approved Filsuvez, a topical gel treatment for partial thickness wounds associated with DEB and JEB. This is the first approved treatment for EB in any market.

Thanks to EB Research Network for some of these milestones.