Welcome to The Lee Smith Foundation Website
We need your help for our children’s Patient Trial with the unique new version of our Gene Therapy. You will be helping to save the lives of critically ill children at Great Ormond Street Hospital, London. Your money will be used to treat children suffering from cancer, leukaemia, fatal immunological disorders and AIDS. Once this 3 year Trial is completed, The Lee Smith Foundation’s new Gene Therapy will be made available to children and adults Worldwide.
In the past, the support that we have received has enabled our work to reach the stage where we are now ready to treat patients with our groundbreaking treatment under the supervision of Professor Adrian Thrasher.
Registered with the Charity Commission in 1982, The Lee Smith Foundation was founded by Jon Smith in memory of his wife Lee who died of Leukaemia at the age of 29. It was Lee’s dying wish that others should not suffer as she did. Since then, Lee’s Charity has helped to save thousands of lives – this could not have been achieved without the generosity of people like you. We also have a Lee Smith Foundation scientist in Wales, working on placental stem cell/laser light therapy, plus a cancer laboratory at Middlesex University, London where our work has included a cancer vaccine and nanoparticle technology. We work with the most eminent professors and doctors.
Due to the challenging economic climate, patients need your help more than ever in order for our £200,000 Patient Trial to go ahead. A grant per year for 3 years will make a real difference but anything you can give will be gratefully received. As a supporter, we will be delighted to promote you on our website and printed material.
Help to eliminate the pain and trauma caused by these terrible diseases.
Please phone me on 020-8958 6118 or email firstname.lastname@example.org if you need any further information. We look forward to hearing from you.
Kindest personal regards,
THE LEE SMITH FOUNDATION GENE THERAPY PATIENT TRIAL
Gene therapy has promised much for many years, and a range of clinical projects are now showing strong signs of efficacy, indicating that this field of technology will soon enter into mainstream medicine for a wide range of diseases (see references 1-8 as examples). There are many reasons contributing to these encouraging developments as the studies showing clinical promise cover several different diseases and employ a variety of genetic medicines (vectors), ranging from simple oligonucleotides through to replicating lytic viruses. However one crucial unifying feature is that they all focus on realistic and achievable objectives. Careful selection of disease targets on the basis of the vector systems available is therefore an essential pre-requisite to success. A number of these notable clinical advances were recently highlighted at a collaborative congress held in Brighton UK between the European Society of Gene & Cell Therapy and the British Society for Gene Therapy1 (http://www.esgct.eu/congress/2011/ ).
The Molecular Immunology Unit at the Institute of Child Health, allied with Great Ormond Street Hospital has pioneered the development of novel treatments for children born with inherited diseases and also for those who develop cancer. Over the last ten years, developments in the laboratory, many of which have been supported by the Lee Smith Foundation, have been translated into genuine clinical benefits in patients. One of the most striking of these has been in the treatment of severe inherited immunodeficiency (so called ‘bubble baby disease’ because the children are born without any protection against infections) by gene therapy. Whereas many patients can be successfully cured by conventional bone marrow transplantation, for those who don’t have a good donor, the risks and complications are high. Gene therapy has revolutionised the potential to treat these patients by offering a way to fix the problem in the child’s own bone marrow. These pioneering treatments are among the first to demonstrate the huge potential for genes to be used as medicines and opens up the scope for treatment of many other serious diseases. In the first phase of trials at Great Ormond Street Hospital, we have now treated over 30 patients, making us one of the leading groups worldwide.
Using the same principles, we can now offer more effective and safe treatments using technological advances that have been recently developed in the research laboratory. We are at the point where these highly novel agents (‘world firsts’) can be used in the clinic for the first time. At present very few Centres can offer gene therapy as a treatment because of the complex infrastructure required both in terms of clinical laboratory space and expertise. We have therefore developed a substantial programme that enables us to do this, including construction of state-of-the-art clinical laboratories where patient cells are treated. Implementation of ‘first-into-man’ studies in patients is expensive (£500K-£3M per disease target), although economic benefits from improved healthcare will make this treatment option relatively cheap when established in mainstream medicine. These studies are necessarily funded by large grants obtained from the Medical Research Council, Leukaemia Research Fund, Wellcome Trust, and the European Union. However, the regulatory process (as for any medicine) is complex, and can slow delivery of new therapies to patients. For this reason we have recently developed a programme based on ‘specials’ which are unlicensed medicines that can be administered to patients at the discretion of the treating physician outside the confines of a formal clinical trial. This is regulated properly by ethics committees and the Medicines and Healthcare products Regulatory Agency (MHRA), but enables us to streamline delivery of new treatments to patients, and also to establish the conditions for subsequent formal clinical trials if these pilot treatments show promise. At GOSH, we are running gene therapy clinical trials for several diseases including severe combined immunodeficiency and leukaemia in both children and adults (in collaboration with Professor Hans Stauss, Royal Free Hospital). We are also in advanced stages of treatment development for other immunodeficiencies (such as chronic granulomatous disease, one patient treated recently on a ‘specials’ basis), inherited blistering skin disease (epidermolysis bullosa), infectious disease (HIV), and other cancers (including liver cancer). Before these latter applications reach clinical trial, we intend to treat several patients in each category using our ‘specials’ license. Although the infrastructure exists to support these treatments, the costs of the vector (per patient), laboratory costs (including reagents and personnel) to transfer the genes to patient cells, and monitoring costs of patients after treatment are not covered. Our proposal is therefore to provide financial costs for treatment of patients with any of these diseases treated under the ‘specials’ legislation. This provides an opportunity for you to support the delivery of highly novel treatments to real patients with a variety of diseases for which existing therapies are either unsatisfactory or non-existent. This will also form the basis for later more substantial trials in larger numbers of patients. We estimate that for each patient (irrespective of the disease target) the costs will range from £20-40K, meaning that £200K would support treatment of 5-10 patients (a detailed breakdown of estimated costs per patient is available on request, although will vary between individual diseases and patients). The time frame for these treatments would be less than 3 years, but we would provide regular updates on patients treated under this protocol as they occur.
Cirak, S. et al. Exon skipping and dystrophin restoration in patients with Duchenne muscular dystrophy after systemic phosphorodiamidate morpholino oligomer treatment: an open-label, phase 2, dose-escalation study. Lancet 378, 595-605 (2011).
Booth, C., Gaspar, H.B. & Thrasher, A.J. Gene therapy for primary immunodeficiency. Curr Opin Pediatr (2011).
Bainbridge, J.W. et al. Effect of gene therapy on visual function in Leber's congenital amaurosis. N Engl J Med 358, 2231-2239 (2008).
Jessup, M. et al. Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID): a phase 2 trial of intracoronary gene therapy of sarcoplasmic reticulum Ca2+-ATPase in patients with advanced heart failure. Circulation 124, 304-313 (2011).
Nathwani, A., Tuddenham, E.G.D., Rangarajan, S., Rosales, C., McIntosh, J., Linch, D., Chowdary, P., Riddell, A., Jaquilmac Pie, A., Harrington, C., O'Beirne, J., Smith, K., Pasi, J., Glader, B., Rustagi, P., Ng, C., Kay, M., Zhou, J., Spence, Y., Morton, C., Allay, J., Coleman, J., Sleep, S., Cunningham, J., Srivastava, D., Basner-Tschakarjan, E., Mongozzi, F., High, K., Gray, J., Reiss, U., Nienhuis, A., Davidoff, A. Adenovirus-Associated Virus Vector–Mediated Gene Transfer in Hemophilia B. The New England Journal of Medicine 10.1056/NEJMoa1108046 (2011).
Perez, E.E. et al. Establishment of HIV-1 resistance in CD4+ T cells by genome editing using zinc-finger nucleases. Nat Biotechnol 26, 808-816 (2008).
Porter DL, Levine BL, Kalos M, Bagg A, June CH. Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N Engl J Med. 2011 Aug 25;365(8):725-33. Epub 2011 Aug 10.
Kaufman, H.L. & Bines, S.D. OPTIM trial: a Phase III trial of an oncolytic herpes virus encoding GM-CSF for unresectable stage III or IV melanoma. Future Oncol 6, 941-949 (2010).
Professor Adrian Thrasher
Cheques payable to: The Lee Smith Foundation Limited. (Post to:The Secretary
The Lee Smith Foundation Ltd, First Artist House, 85A Wembley Hill Road, Wembley, Middx. HA9 8BU.) Tel: 020-8958 6118. Email: email@example.com Registered Charity No.1112905. Trustees: J Smith, H Ingram, S Bourne