Large pharmaceutical company shines spotlight on EB
In big news for the EB community, it was announced on Tuesday that the global pharmaceutical company, Shire, has signed an agreement to acquire Lotus Tissue Repair, the biotech company currently developing a protein replacement therapy for dystrophic EB (DEB).
Shire intends to progress the development of this therapy, which has the potential to be the first of its kind for EB. It involves the delivery of recombinant (man-made) collagen 7 protein (rC7) to patients who are missing or have dysfunctional collagen 7. The therapy approach originally emerged from the research lab of Dr. David Woodley and Dr. Mei Chen, University of Southern California. Currently, driven by Lotus, it is at the ‘late pre-clinical' stage - the final phase of development, prior to testing in patients and, so far, the results look very promising.
Dr. Mark de Souza, the driving force behind Lotus Tissue Repair, will work closely with Shire over the coming year to ensure a smooth transition of the programme. A big part of his role, in that regard, will be facilitating the continuance of the many key relationships that he has established in the EB community, with the team at Shire. "I know that Shire Human Genetic Therapies will be a great home for our rC7 program" said Mark. "I am confident that the Shire team will complete the job that we started and that they will do so in a manner that will bring rC7 to patients as quickly as possible. I look forward to the day when this therapy will enter the clinic and I hope will change the lives of patients and families with DEB."
Shire has a strong focus on rare human genetic diseases and considerable expertise in protein replacement therapies. This potential product for EB should therefore fit well with the company's interests and the expertise and resources available to the company bode well for the future of the protein replacement therapy. Also very reassuringly, Shire has a prior interest in EB, in the form of a wound healing product for EB, currently in development. This product, referred to as ABH001, is a biological skin substitute, created by growing human skin cells on a mesh that can be absorbed by the body.
John Dart, Chief Operating Officer with DEBRA International has welcomed the news of the Lotus acquisition by Shire and said "It is immensely encouraging that the future of this exciting potential therapy is in safe and experienced hands. We have worked closely with Lotus and look forward to doing so with the Shire Human Genetic Therapies division, to get protein therapy into the clinic."
For more details, see this press release from Shire.
A link to the DEBRA Ireland Research and Advocacy update, October 2012
A link to the DEBRA Ireland Research and Advocacy update, April 2012
A link to the DEBRA Ireland Research and Advocacy update, December 2011
A link to the DEBRA Ireland Research and Advocacy update, September 2011
The Risky Business of ‘Stem Cell Tourism'
Stem cell treatments are increasingly becoming an everyday topic of conversation and more and more patients are travelling to avail of the latest ‘miracle cure'. Sadly however, many of the stem cell therapies offered are nothing more than a money-making racket for the bogus clinics that offer them. Stephen Sullivan, Director/Chief Scientific Officer of the Irish Stem Cell Foundation has written an excellent article on the issue and provides pointers on how to distinguish the genuine from the fake in the world of ‘stem cell tourism'.
Gene therapy trial starting in the US
Researchers in Stanford, California have begun recruiting patients for a gene therapy trial for RDEB. Skin cells will be taken from the enrolled patients, the missing collagen 7 gene replaced in them and the cells then grown into sheets in the lab. These sheets will then be grafted back to wounded areas on the patient's skin. The purpose of the trial is to test how safe and effective this approach is and is currently limited to adults, resident in the US. The initiation of such gene therapy trials for EB has been a long time coming and we are very pleased to see such a hopeful approach get underway. For more information and an excellent short video click here.
Botox to treat EB Simplex
Botox injections could soon take on a whole new interest for people with EB Simplex, beyond their cosmetic appeal for the masses. A group led by Dr. Carl Swartling in Uppsala, Sweden are undertaking a clinical trial to test the effectiveness of botox in reducing pain in the soles of the feet for EB Simplex. Blistering, and therefore pain, is often exacerbated for patients during the summer months, due to increased sweating. The research team have chosen to test the effectiveness of botox because it acts to block the chemical signals from the nerves that stimulate sweat.
Injections of botox under anaesthesia are being compared to injections of a simple salt solution, for effectiveness in reducing pain in the soles of the feet. Initial results indicate that there is a reduction in sweating and a considerable reduction in pain, for an average of 3 months. The treatment is somewhat complicated by the need for anaesthesia, due to the sensitivity of the soles, but one treatment a year, to get through the summer months, may be enough to make a big difference to quality of life.
As there have been no treatments for EB simplex to date, we feel this is an exciting development and will keep you updated on progress. For a more detailed article on this treatment please click here.
DEBRA Ireland researcher wins prestigious science prize
(Posted October 2010)
DEBRA Ireland researcher, Dr. Wenxin Wang, was recently honored with the Science Foundation Ireland (SFI) Prize in Regenerative Medicine, at an international conference focusing on tissue engineering and regenerative medicine. Wenxin holds the post of Lecturer in Functional Biomaterials at the National University of Ireland Galway, a position co-funded by DEBRA Ireland and SFI. The TERMIS-EU conference, at which Wenxin was awarded his prize, was held in Galway over four days during the summer of 2010.
The award was judged by an international advisory panel and was presented to Wenxin for his outstanding achievements within the field of tissue engineering and regenerative medicine. Wenxin's research focuses on the development of new technologies for wound healing applications, with a particular focus on the treatment of wounds in EB patients. Wenxin is delighted and encouraged that his work has been recognised in this way and he continues to strive to develop treatments to improve the quality of life for EB patients. We congratulate Wenxin on this achievement.
EB Project in California Receives Large-Scale Funding
(Posted December 09)
In a very exciting development for EB research, a large multi-disciplinary group of scientists in Stanford University, California have received $11.7 million to develop a new approach for the treatment of dominant dystrophic EB (DDEB). This group is led by Prof. Alfred Lane and includes DEBRA Ireland-funded researcher Professor Peter Marinkovich. The aim of the research is to use a relatively new technology in stem cell research, known as iPS cells (induced pluripotent stem cells) to treat the condition. Stem cells are the focus of much research as they have the ability to develop into other types of cell and therefore, have many possible uses in medical applications. Their use presents many problems however, including the ethical issues associated with the use of embryonic stem cells and the fact that adult stem cells can be hard to find and limited in the cell types which they can become. iPS cells on the other hand, are cells taken from an adult but which have been ‘reprogrammed' so that they can become any cell type and therefore overcome many of these problems.
In this proposed research project, the scientists plan to take cells from the DDEB patient to be treated, create iPS cells from them and then correct the genetic fault in them. These corrected iPS cells will be converted to skin cells and grown into ‘sheets' in the lab, which can then be used for skin grafts for the patient. As the genetic fault has been corrected in them, the grafted skin sheets should behave like normal skin and be resistant to blistering.
The review panel who assessed the proposed research felt that it will have enormous technical challenges to overcome but that it holds real promise for the treatment of DDEB. The calibre of the assembled team of scientists was a strong factor in favour of its funding. This is an astonishing amount of funding for research into such a rare condition but the review panel felt that skin was a good ‘model' to test iPS cells on and that this research will have broader applicability to the medical field in general. This funding represents good news for Ireland's DDEB patients, many of whom are still very young and who will hopefully benefit from this research as they get older. The research will also have positive implications for other forms of EB.
New Dublin Dermatology Institute
(posted May 2009)
In an exciting development for skin research, plans for the first dermatology research centre in Ireland are underway. The centre will be based in University College Dublin (UCD) and has been named the Charles Institute, in honour of Andrew Charles, the founder of the City of Dublin Skin and Cancer Hospital at Hume Street, which closed its doors in 2006.
The vision for the Institute came from the Board of the Hume Street Hospital who were eager to ensure that the proceeds from the sale of the hospital site would benefit Irish dermatology patients. They have provided two thirds of the costs for the 2,000 square metre Institute and have joined forces with UCD who are very enthusiastic about the project. The Institute is well placed, in the heart of UCD's research network and with strong connections to Dublin hospitals, to ensure the any scientific discoveries are translated into real benefits for patients. The Institute will also play a central role in the education of healthcare professionals in dermatology practices.
The Charles Institute will be staffed with up to 50 researchers who will undertake cutting edge research into skin conditions. While the exact nature of this research remains to be defined, DEBRA Ireland is hopeful that this centre of excellence in dermatology will be of benefit to Irish EB research and, most importantly, to EB patients.
For more information on the Institute and a 3-D model of the building please see the UCD website.
Interview with Dr. Wenxin Wang, new EB researcher in Galway
From the June 2009 DEBRA Ireland newsletter
Dr. Wenxin (pronounced Wenchin) Wang has recently started EB research in the University in Galway. He is a very talented and ambitious scientist, not to mention a very lovely person, and DEBRA Ireland are extremely grateful to have what we believe will be a very fruitful relationship with him. We asked him some questions about himself.
Tell us a little about yourself Wenxin?
I was born and brought up in Tianjin, China. I discovered during my school years that I had a passion for science and afterwards I attended Sichuan University where I studied Polymer Science and Engineering. In 1999, I received my Ph.D. from Shanghai Jiao Tong University, which focused on materials known as fluoropolymers. In 2000, I moved to Europe and undertook research in the University of Liege in Belgium for a year. Before coming to Ireland I spent seven years as a senior researcher in the University of Nottingham. Through all the years of my research I have always focused on the development and use of novel chemicals and materials for applied applications, especially for medical purposes. My wife is also a scientist and we have a twelve year old daughter named Lucy.
How did you end up undertaking EB research?
In the summer of 2008 I saw an advertisement for a job in the university in Galway, in the Network of Excellence for Functional Biomaterials (NFB). I had heard that Galway was a great place to live and the research undertaken in the university is of very high quality and so I applied. I was successful in obtaining the position and then moved to Galway in September last year. Soon afterwards I applied for the position of Lecturer in Functional Biomaterials in NFB, funded by Science Foundation Ireland and DEBRA Ireland. After a tough interview process I was very excited to be awarded the position and immediately began to focus my expertise on treatments for EB.
What do you hope to achieve in your EB research?
The current goal of my research is to develop an advanced dressing system for the treatment of the recessive dystrophic form of EB. The basis of this wound dressing is miniature devices known as dendritic polymers. At room temperature, the dressing exists in a liquid form. However, upon application to wounds, the solution quickly forms a gel to cover and seal the wound site. In addition this dressing will act to deliver copies of the collagen 7A1 gene which is missing in these patients. This "smart dressing" should also have direct applications for other forms of EB. I really believe that my research will make a contribution to the development of treatments for EB and I look forward to working closely with DEBRA Ireland in the years to come.
EB researcher receives rare disease research award
(posted April 2009)
Professor Leena Bruckner-Tuderman, an eminent EB researcher based in Freiburg, Germany, has received a top award for her research into EB. The German award, known as the ‘Eva Luise Köhler Research Award for Rare Diseases', was presented to her in a ceremony that took place in Berlin in March 2009. The award aims to honour individuals who have made an outstanding contribution to the study of a rare disease. Professor Bruckner-Tuderman has undertaken EB research and treated EB patients for many years. Specifically, the award was given to her in recognition of a project that she initiated on ‘Molecular disease mechanisms and preclinical testing of biological therapies for dystrophic epidermolysis bullosa'. DEBRA Ireland would like to congratulate Professor Bruckner-Tuderman on a well-deserved honour.
Focus on London School of Medicine and Dentistry
(From the February 2009 DEBRA Ireland newsletter)
For some individuals with severe forms of EB, a type of skin cancer call squamous cell carcinoma (SCC) is a persistent worry. This form of cancer is found in the general population but for reasons currently unknown, it is particularly aggressive in EB patients.
DEBRA Ireland is currently funding two projects on SCC with Professor Edel O'Toole, a highly respected researcher and consultant dermatologist, in Barts and the London School of Medicine and Dentistry. Dr. O'Toole, originally from Co. Mayo, received her medical degree from NUI, Galway. She was inspired to undertake research into EB during her time spent as a registrar in the EB unit at St. James Hospital in Dublin, in 1992. Together with two members of her team, Dr. Vera Martins and Dr. Manos Papadakis, Edel is focused on understanding what makes EB patients more susceptible to SCC than the general population and why it then spreads so rapidly. To answer these questions, they are analysing changes at the molecular level in tumour cells from EB patients. With DEBRA Ireland funding, they have identified a gene, called Axl, that they believe to be playing a critical role in tumour development. They are currently designing drugs to block Axl, in the hope of preventing the growth of tumours.
In addition, the team has found some evidence that molecules known as chemokines may also be playing a critical role in the formation and spread of skin tumours. Chemokines are small molecules that enable cells to talk to one another and are involved in influencing the way cancer cells move from the skin to other organs. Understanding more of the involvement of chemokines in this type of cancer will open up other avenues for therapy. There are already anti-chemokine drugs being developed for other types of cancer, making the possibility of treatment for EB skin cancer all the more feasible. Edel's exceptional talent as a researcher has recently been recognised through her appointment as Professor of Molecular Dermatology at the London School. DEBRA Ireland would like to take this opportunity to congratulate Edel on her professorship and to thank her for her commitment to EB research.
Focus on Stanford University, USA
(From the June 2008 DEBRA Ireland newsletter)
For a minority of individuals with EB, specifically some of those with the recessive dystrophic form, the possibility of skin cancer is unfortunately an ever persistent worry in adulthood. Why exactly these individuals are susceptible to skin cancer is still not fully clear but is certainly related to the lack of collagen 7 protein in their skin. Collagen gives the skin strength and elasticity which is why you will often hear it mentioned in adverts for anti-wrinkle creams. In individuals with recessive dystrophic EB, a tiny problem (or mutation) in the gene for collagen 7 means that there is either very little or none of this form of collagen produced in their bodies. This leaves the skin weaker, susceptible to blistering and, in some cases, at risk of cancer. There is currently much research being undertaken around the world to look at why the lack of collagen make these individuals more susceptible to skin cancer and many researchers are investigating possible treatments for the cancer.
DEBRA Ireland is currently funding Professor Peter Marinkovich in Stanford University in the USA to undertake research into a potential cure for skin cancer in EB. His particular approach involves the use of antibodies. Antibodies are the little soldiers of our immune systems that patrol the body seeking out bacteria and viruses to destroy. Peter is using the ‘seek and destroy' ability of the antibodies to target proteins which play a role in the many changes that occur in the skin during the formation of a tumour. He is hoping to use the antibodies to block the action of these proteins and in this way to stop the formation of tumours.
Peter is also part of a team in Stanford University that is about to undertake the first clinical trial into EB in the USA. The term ‘clinical trial' simply refers to the testing of a medicine in humans. In this particular case they will be testing a method for gene transfer (which will be known as gene therapy if it is successful). Their aim is to replace the missing collagen 7 gene in sections of skin in individuals with recessive dystrophic EB. They will do this by taking some of the individual's own skin cells and inserting into them the missing collagen gene. The cells will then be grown in sheets which will be grafted back to chronic wounds on the same individual's skin. The first consideration of the trial is safety and individuals with EB are currently being screened to see whether they qualify for the trial. This trial is currently limited to adults who are resident in the USA but hopefully will have implications worldwide in the near future. Click here to see more information about this exciting undertaking.
Focus on National University of Ireland, Galway (NUIG)
(From the February 2008 DEBRA Ireland newsletter)
DEBRA Ireland has been funding Professor Abhay Pandit's research since 2004, when an article in the Irish Times first drew our attention to the relevance of Abhay's work to EB. Abhay and his team are based in the impressive ‘National Centre for Biomedical Engineering Science' in NUIG. The group's research there has been going from strength to strength, a fact that was recently recognised by the awarding of a highly competitive ‘Strategic Research Cluster' grant to Abhay and his collaborators, by Science Foundation Ireland (SFI).
The Galway team currently focus on two different aspects of EB research; wound healing and the use of nanotechnology to deliver therapies. One of the more difficult problems encountered by individuals with EB is the presence of persistent, and sometimes non-healing, wounds. Dr. Gopinath Damodaran is currently working on a treatment to encourage wounds to heal faster. He has been successfully developing artificial skin in the lab, consisting of a ‘scaffold' of proteins found naturally in the body. When proven safe, this scaffold could be placed over a wound and would ‘spur on' the skin to heal itself. The team are also taking this approach one step further and looking at using the scaffolds to delivery therapeutic drugs to the skin of individuals with EB.
Other members of Abhay's team, Dr. Gildas Réthoré and Suzanne O'Rorke, are taking an alternative approach to developing a therapy for EB. This method involves the use of nanotechnology and they are becoming very proficient at making nanoshells in the lab. Nanoshells are essentially microscopic spheres with a hollow core, into which a therapeutic agent may be inserted. Gildas and Suzanne are devising methods to tag the nanoshells with ‘homing devices', which will lead the nanoshells to the cells of the body where they are required and where they will deposit their therapeutic cargo. One of the appeals of this approach is that this method of therapy delivery would be capable of targeting, not just the skin cells, but also the internal tissues which can be affected in individuals with EB.
Stem cells in EB Research
(Posted November 2007)
What is a stem cell?
Obviously we have many different cell types in our bodies - heart cells, liver cells, skin cells... A heart cell is always going to be a heart cell and doesn't have the ability to become a skin cell, for instance. A stem cell however, is one that has the potential to become many different cell types. There are different categories of stem cell, which have more or less potential to become other types of cells. Embryonic stem cells (taken from a developing embryo and referred to as ES cells) are the ultimate in stem cells because they can become ANY type of cell. Naturally however, there are ethical issues to be considered in the use of embryonic stem cells and because of this, many regulatory issues surround their use. There are also stem cells in adult tissues but they are more limited in the types of cell that they can become. For example, skin stem cells can only become one of the types of cells found in our skin. They are harder to find, harder to grow and of more limited use than ES cells
Stem cells in EB research
There is a considerable amount of EB research making use of stem cells at present. So far however, this research has mainly focused on the use of skin stem cells taken from adults. In this case, the scientists take the adult stem cells from the patient, grow them up in a petri-dish and introduce into them the gene that is missing in the patient e.g laminin. They then graft the cells back to the patient's skin to heal the patient's wounds.
Stem cell breakthrough
The big excitement about stem cells at the moment is because two different groups, in Japan and the US, have taken human adult cells (well, in one case they were actually taken from a baby) and essentially ‘reprogrammed' them to behave as if they were ES cells. They did this by using a virus to carry four genes into the cells, which then acted in such a way as to make the cells believe that they were ‘starting over'. Obviously this over-rides all the issues relating to using cells from embryos and yet these cells (which they are calling iPC cells) have all the advantages of ES cells. Of course, there is always a hitch or two and in this case the biggest problem is that some of the cells created this way become cancerous. If these cells were introduced into patients they could actually give them cancer. Hopefully this is a problem that will be resolved in the near future however.
What does this breakthrough mean to EB research?
In order to avoid an immune reaction, a stem cell therapy should ideally use cells from the patient's own body. Finding stem cells in an adult patient is difficult and particularly so in the case of an EB patient. This new development will make it much easier to obtain a source of cells for a stem cell therapy. As I have mentioned, adult stem cells are limited in the types of cell they can become. The new iPC cells are much more closely related to the younger, fitter and smarter ES cells! This will allow researchers much more flexibility in the treatment EB patients and will undoubtedly open up other avenues of research. Due to the ethical issues, there is currently no ES cell research in Ireland. Now that another approach has been identified it will open the door to the possibility of our own EB researchers developing new avenues of stem cell research. Interestingly, these iPC cells started out life as skin cells and hopefully, one day we will see them go full circle to become a skin stem cell therapy.