About dystrophic epidermolysis bullosa (DEB)

What is dystrophic epidermolysis bullosa (DEB)?
Epidermolysis bullosa (EB) is a group of rare genetic skin diseases of which Dystrophic EB (DEB) is one of the most severe forms. There are two main types of DEB – the dominant form (DDEB) when the affected person inherits the altered gene from only one parent and the recessive form (RDEB) when the affected person inherits one copy of the altered gene from each parent. RDEB tends to be generally more severe than DDEB.

People with DEB have blistering of skin and mucosal membranes that line many tracts and structures of the body, such as the mouth, food pipe etc. Children with DEB are often called ‘Butterfly children’ as their skin is as fragile as the wings of a butterfly. This fragility results from a very weak connection between the dermis (inner layer) and the epidermis (outer layer) of the skin. People with DEB live with constant pain and have a high risk of malnutrition and infections. Symptoms include poorly healing wounds, skin infections, fusion of fingers and toes (pseudosyndactyly), anemia, gastrointestinal tract problems and with adulthood some develop very aggressive forms of squamous cell carcinoma (skin cancer).
What causes DEB?
DEB is caused by mutation(s) (or mistakes) in a gene in the DNA called the COL7A1 gene. This gene is responsible for the formation of collagen type VII (C7) protein that forms anchoring fibrils that bind the dermal (inner) and epidermal (outer) skin layers together. The mutations can occur in different parts of the COL7A1 gene and cause loss or malfunction of the anchoring fibrils. This leads to the fragile skin in DEB patients.
Treatment
Currently, there are no approved treatments available that target the underlying cause of DEB. Patients receive treatments that focus on disease management, prevention of complications and prevention of the formation of new blisters. There are palliative treatment options focused on wound care (bandaging, prevention of infection, better wound healing), pain management and itch management. Other points of attention are bone care, nutrition (due to eating difficulties), oral care and eye care. In addition there is a close surveillance for skin cancer, to which some DEB patients are especially vulnerable.

About QR-313

ProQR is developing an investigational drug called QR-313 for people that have DEB due to a mutation in a specific part of the COL7A1 gene called exon 73. We estimate there are approximately 2,000 patients in the Western world that have DEB due to a mutation in this specific part of the gene. QR-313 is designed to exclude exon 73 from the COL7A1 RNA. This approach is also known as exon skipping.

RNA is the "blueprint" for protein synthesis. Skipping of exon 73 in the "blueprint" is expected to lead to a shortened but functional C7 protein. By restoring the functionality of C7 protein QR-313 aims to bring back the anchoring fibrils and strengthen the skin. This should result in better wound healing and prevent blistering. QR-313 is a water based gel (hydrogel) that will be applied directly onto DEB wounds (topical administration).

QR-313 has received orphan drug designation from the U.S. Food and Drug Administration and European Medicines Agency.

Beyond QR-313 we are working on multiple other programs targeting other mutations causing DEB.

Clinical trials
QR-313 is in the pre-clinical phase of testing. We plan to start a DEB wound observational study as it is important to better understand the behavior of DEB wounds over time. In addition, we plan to start a first clinical trial of QR-313 as soon as possible in people that have the recessive form of DEB (RDEB) due to mutations in exon 73 of the COL7A1 gene. Updates will be posted to this website so please check back regularly.

Information for patients

QR-313 is an experimental medicine that we are developing for people with dystrophic epidermolysis bullosa (DEB) due to mutations in a specific part of the COL7A1 gene called exon 73. QR-313 is a water based gel (hydrogel) that will be applied directly onto DEB wounds (topical administration). We are making good progress in the early stages of the development of the medicine, but we have yet to start the first clinical trial in people that have the recessive form of DEB (RDEB) and QR-313 is not yet available for patients. For more information about the program please visit this page since we will post regular updates here first. If you have any other questions please read the FAQ or contact us through the contact form and we will be happy to answer any question you have.

FAQ

What is QR-313?
QR-313 is an experimental medicine that is designed to treat dystrophic epidermolysis bullosa (DEB) caused by mutations in exon 73 of the COL7A1 gene. By restoring the functionality of C7 protein QR-313 aims to bring back the anchoring fibrils and strengthen the skin. QR-313 has shown promising results in the lab but has not been tested in humans yet.
When and where will QR-313 be tested?
ProQR is moving this program towards first clinical trials in people as soon as possible. Updates will be posted to this website so please check back regularly.
Which known mutations are found within exon 73 of the COL7A1 gene?
Different mutations cause DEB. In the DEB registry database you can search for all known mutations to date and see in which exon of the COL7A1 gene they are found. We recommend that you talk to your physician if you have any questions regarding mutations.

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