In this first update on the activities and progress of The Stop ALD Foundation (SALD), we want to first and foremost thank you for your participation in the fight to seek out and develop promising therapies to prevent, diagnose, and cure adrenoleukodystrophy (ALD). SALD's guiding principal is to make investments using your generous donations that will most effectively lead to viable therapies in the shortest time frame. Because of the rarity of and lack of attention paid to ALD, even when compared to diseases with similar levels of incidence, research money devoted to fighting the disease is comparatively miniscule. Thus, every dollar SALD strategically deploys in the fight can really make a difference. We want to update you on SALD's progress to date.
SALD ONGOING PROJECTS IN CONNECTION WITH TREATMENT OPTIONS
Treatment options for ALD sufferers are extremely limited. The only uniformly accepted and recommended therapy is bone marrow transplant (BMT), but the procedure itself is risky and not even an option for all sufferers of the disease. In fact, BMT is only suitable during a relatively narrow window of opportunity before ALD has progressed too far. As BMT does not generally reverse ALD, which continues to progress for six to 12 months even after a successful procedure, lack of an early diagnosis of the disease can mean that a patient will not benefit from the procedure. BMT may also not be appropriate for some patients because there is no good bone marrow match found. Additional therapies must be developed to fight ALD.
- Gene Therapy
- Cell Cloning Therapy
- Mesenchymal Stem Cell Therapy
1. GENE THERAPY
One of the promising new therapies, which SALD is helping to develop, is gene therapy. Several members of SALD met with Dr. Patrick Aubourg, a researcher in France who is the only doctor in the world developing gene therapy for ALD. Dr. Aubourg has published in The New England Journal of Medicine, Nature, Lancet and other top-tier journals. His published work concerns the diagnosis, therapy and understanding of ALD disease mechanisms. Dr. Aubourg has been doing important research related to ALD gene therapy for over eight years, but his promising work has been slowed by the lack of qualified personnel and resources devoted to it. In keeping with SALD's policy of channeling resources to promising therapies in development, SALD saw an opportunity to enhance and accelerate Dr. Aubourg's research. To that end, SALD has sponsored a tremendously skilled and experienced post-doctoral student to work in Dr. Aubourg's lab. She is already running various experiments in the lab in Paris in preparation for a human clinical trial.
To carry out the human clinical trial, researchers will need a large quantity of gene therapy "product" of the very highest quality. There is only one company, Cell Genesys, in the U.S. currently on track towards making the appropriate product (also called a vector) in the near future, and SALD is proud to say that the company agreed to cooperate with SALD's plans for the human trial. This development is a direct result of a series of meetings organized or implemented by SALD and held throughout the U.S. and Europe between Cell Genesys, SALD scientific advisors, various ALD researchers, FDA advisors, and SALD members. The project was officially launched by Cell Genesys on March 1, 2002. As Cell Genesys is only providing the vector, SALD itself is driving this huge but exciting project and is responsible for getting the actual clinical protocol up and running. Ongoing meetings and discussions are occurring even now to accomplish this, and SALD will commit additional resources and personnel to the project over the coming year. SALD aims to have the project protocol and plan reviewed and approved by relevant governmental advisory and regulatory committees by Q2 2003.
In another development on the gene therapy front, several members of SALD met in March 2002 with Dr. Alain Fischer in Paris to specifically discuss ALD and gene therapy. This meeting was important because Dr. Fischer is the only researcher in the world so far who has, by most counts, cured a fatal pediatric genetic disease. Everyone agrees the children he treated are now basically fine; however, it has only been a few years and so it is too early to call it a definitive cure. Dr. Fischer will be one of the key participants in the European arm of our gene therapy clinical trial.
2. CELL CLONING THERAPY
In another promising area of research, SALD is working with Advanced Cell Technology (ACT), a highly innovative company in Massachusetts working in the area of therapeutic cloning. The concept is that if someone has liver failure, for example, and a donor liver is not available, doctors could remove some cells from a part of the person's body (likely the blood, skin or from the organ in question itself) and then reprogram them to develop into the required tissue once they are returned to the person's body. The obvious advantage of therapeutic cloning is that there are no rejection problems typical with transplanted tissue or organs because the cells come from the person's own body.
A similar scenario with ALD would be as follows: cells are taken from a person with ALD, the defect causing the ALD is repaired, the cells are expanded and then reprogrammed to become the type of cells used in the one successful model for treating ALD that already exists: BMT. Therapeutic cloning sounds farfetched, but it is only a matter of refining the technology because the process was recently proven to be successful in an animal model. Members of SALD met with the CEO and other officers of ACT, and the company is committed to helping the Foundation. So far, ACT has underwritten the bulk of the expense of this project. SALD is in contact with ACT on a regular basis and both sides meet to discuss progress with the project. SALD is constantly tweaking its end of the protocol, which involves providing ACT with various ALD samples.
3. MESENCHYMAL STEM CELL THERAPY
SALD is also contributing resources to research involved with another type of cell called a mesenchymal stem cell (MSC). This cell has shown promise in terms of differentiating into various brain cells. With ALD, children get sick and die because they lose myelin, the "white matter" of their brains. Recently MSCs have shown promise in the area of remyelinating brains. On April 8, 2002, SALD conducted a meeting with the world's leading experts in MSCs (which are currently used in the treatment of some other diseases) along with ALD experts so that MSCs and their potential as an ALD therapy could be explored. The parties outlined a clinical trial that would involve giving MSCs to patients in the more advanced stages of ALD who have already elected BMT and have found a perfect bone marrow donor match. Because of the progression of the disease for a period after BMT, the hope is that the addition of MSCs to the protocol will allow for cells to get into the brain much sooner and ultimately improve the long term outcome. Much of this theory is based on preclinical data performed by researchers who attended the April 8 meeting. One of the proposed primary investigators, Dr. Ed Horwitz from St. Judes Hospital in Memphis, is one of the few hematologists in this country that already has experience giving MSCs to children with a genetic disease. He has a track record and is eminently qualified and motivated to help these "index case" patients, typically the first ones to be identified with a genetic disease in a family.
SALD continues to explore one of the most painful aspects of this disease, the timing of its onset. A child is diagnosed with the ALD defect in his genes. Will he develop the devastating disease as a child or will he get adult-onset ALD, itself a physically disabling illness with a 30% chance of fatal brain involvement? Through SALD's efforts, GlaxoSmithKline (GSK), the world's second largest pharmaceutical company, has initiated a project to help answer this crucial question. By using sophisticated technology (which has cost millions of dollars to develop), GSK researchers will analyze ALD tissue samples provided by SALD and determine if data can be generated to elucidate this issue. This field is called proteinomics.
So many therapeutic options for ALD have not been explored for the simple reason that the world's leading experts in areas like gene therapy, therapeutic cloning, proteinomics, and MSCs go about their fascinating work without ever encountering ALD. Wherever in the world there is a scientist, researcher, physician, biotech concern, or pharmaceutical company working on anything that may potentially advance the world of ALD diagnosis and treatment, you can be sure that SALD will find that individual, group, or company and do whatever is necessary to enlist their aid.
Please let us know if you have any questions about the initiatives of SALD in its fight against this devastating disease. Thank you again for your past, present and future support.