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SCIENTIFIC RESEARCH: Use of variability in national and regional data to estimate
the prevalence of lymphangioleiomyomatosis Room to Breathe For a small group of New Zealand women with a rare but fatal lung condition, Mervyn Merrilees' pioneering research on heart disease offers an unexpected glimmer of hope. Dayby day, Imeleta Maddox's lungs are running out of space. You can almost feel the effort of each laboured breath - the fight to draw in air and the suffocating sensation of never quite getting enough. MILES Trial Results Published The LAM Foundation is extremely pleased and proud to share some outstanding news. The MILES Trial final analysis has taken place and the trial results are reported in today’s on-line version of the New England Journal of Medicine (NEJM). In addition to the trial results, the NEJM also published an editorial which highlights the trial and the role of The LAM Foundation in research advancements The MILES Trial was the first randomized, controlled study designed to develop a therapy for LAM. The primary endpoint was met. Treatment with sirolimus, also known as rapamycin, for one year resulted in a small but significant improvement in FEV1. Frank McCormack, MD, Director of the Pulmonary, Critical Care and Sleep Medicine Division at the University of Cincinnati, was the lead investigator on the study. Dr. McCormack also serves as the Scientific Director of The LAM Foundation, which played an integral role in the success of the trial. In addition to providing supplemental funding, which covered the costs of data monitoring and patient travel reimbursement, the Foundation worked together with the investigators on the education and recruitment of LAM patients. The LAM Foundation would like to take this opportunity to thank the LAM patients in the United States, Japan and Canada who were involved in the MILES Trial. Because of their hope for a treatment and ultimately a cure, they chose to become involved. Trials are not for everyone for a variety of reasons, but for the 111 LAM patients who consented, and the 89 who completed this trial, all LAM patients and their families thank you. Without your courage, a treatment would have been missed. Our gratitude is extended to the generous sponsors who provided the funding. The LAM Foundation would also like to thank Dr. McCormack and all of the professionals and institutions involved in the MILES Trial. Please click here to go to The LAM Foundation’s website for the links to the full New England Journal of Medicine article, the editorial, a press release from the University of Cincinnati and also FAQs about the Trial results. links: The Power of Patient and Family Pays Off There are an estimated five women per million in the United States who suffer from lymphangioleiomyomatosis (LAM), a rare and devastating disease that almost exclusively strikes young women.1-3 These patients have progressive loss of lung function, and many die from respiratory failure. Until recently, a diagnosis of LAM was a medical anomaly, and a woman who received this diagnosis had little cause for hope. The disease was likely to be managed symptomatically by physicians unfamiliar with the disease. > read more New LAM Research A contract has been signed and work begins this month at the Malaghan Institute for Medical Research in Wellington. The Agreement to fund a one year pilot programme of new LAM Research is between the Malaghan Institute's Cancer Cell and Molecular Biology Group and The New Zealand LAM Trust in collaboration with LAM Australasia Research Alliance (LARA).
The Project will investigate the cancer-like properties of LAM cells; in particular, whether LAM cells can grow in culture, under conditions that support the growth of self-renewing cancer cells. The team will investigate whether LAM cells grown in these conditions, express self renewal genes typical of cancer stem cells.This work is designed to be part of a larger study that will explore the feasibility of treating LAM, using the immunological therapies currently being developed for treating cancer. Both the Australian and New Zealand LAM patient organisations which have raised the money for this project wish to thank supporters for their donations that have made this work possible and we wish the research teams well in the first year of this exciting programme. Feasibility of Immunotherapy for Lymphangioleiomyomatosis LAM strikes women during their reproductive years and leaves patients with a much reduced life expectancy at diagnosis. Patients with LAM present with recurrent pneumothoraces, hemoptysis, pleural effusions, and dyspnea on exertion. There is no truly effective treatment available beyond lung transplantation. LAM is definitively diagnosed by detecting expression of the glycoprotein recognized by the antibody HMB45. Differential diagnosis is otherwise difficult, and patients with sporadic LAM typically remain undiagnosed for several years. > more Melanoma–Associated Antigen Expression in
Lymphangioleiomyomatosis Renders Tumor Cells Susceptible to Cytotoxic T Cells Following the identification of underlying mutations responsible for the symptoms incurred in LAM and intracellular signaling pathways affected by TSC1/TSC2 through the mammalian target of rapamycin complex, proposed disease treatments have been aimed at the hyperproliferative responses observed in mutant cells. The mammalian target of rapamycin inhibitor rapamycin has been tested in phase 1 trials with mixed results. > more Molecular Pathogenisis of LAM Lymphangioleiomyomatosis (LAM) is a rare progressive cystic lung disease affecting young women. The pivotal observation that LAM occurs both spontaneously and as part of the tuberous sclerosis complex (TSC) led to the hypothesis that these disorders share common genetic and pathogenetic mechanisms. In this review we describe the evolution of our understanding of the molecular and cellular basis of LAM and TSC, beginning with the discovery of the TSC1 and TSC2 genes and the demonstration of their involvement in sporadic (non-TSC) LAM. This was followed by rapid delineation of the signaling pathways in Drosophila melanogaster with confirmation in mice and humans. This knowledge served as the foundation for novel therapeutic approaches that are currently being used in human clinical trials. > more
As a result of three years of work by The New Zealand LAM Trust, the team of New Zealand and Australian researchers (pictured right) are working against the clock as part of an international collaborative effort to uncover answers to the causes of this rare and cruel disease. Dr Lyn Moir began her work at The University of Pennsylvania in the lab of Dr Vera Krymskaya in June 2007. Dr Moir will return to The University of Sydney in 2008, and it is hoped that funds will be raised to enable her to continue her cell signalling work there. A presentation abstract on the work completed in Philadelphia will be made at the American Thoracic Society's annual meeting in Toronto in 2008 and at the Australasian Thoracic meeting in Melbourne in May 2008. Lymphangioleiomyomatosis Lymphangioleiomyomatosis (LAM) is a rare, progressive, cystic lung disease that occurs almost exclusively in females, usually between menarche and menopause. The hallmarks of LAM are diffuse infiltration of the pulmonary parenchyma with atypical smooth muscle cells, airflow obstruction, pneumothorax and chylothorax, and progressive respiratory failure... > more Australian Scientific Investigation In June 2004 the prestigious UK Journal of Pathology published a Paper from Professor Mervyn J Merrilees, principal investigator,University of Auckland in conjunction with Professor Judith L. Black, University of Sydney. The paper is titled "Matrix Proteoglycans and remodelling of interstial lung tissue in Lymphangioleiomyomatosis (LAM)". This Paper can be seen on line in Wylie InterScience (www.interscience.wiley.com) and is published in J Pathol 2004; no 203: 653-660. Currently, NZ LAM Trust funded LAM science investigation continues at the University of Auckland. Professor Merrilees and his team's recent studies (UK Journal of Path) have shown that LAM is characterised not only by the growth of defective smooth muscle cells, but also by significant amounts of interstitial tissue that contain normal fibroblasts and large amounts of space occupying matrix proteoglycans. Of particular interest is the finding that areas rich in proteoglycans are depleted in elastic fibres which are essential to the proper functioning of the lung during breathing. Prof Merrilees and the team have been working with the drug rapamycin which has been found to be a very effective inhibiter of cell migration. |
The Wellington based work which is part of a proposed three year study will be undertaken by Professor Mike Berridge and his team at the Institute, in collaboration with Dr Lyn Moir from Professor Judy Black's lab at the University of Sydney.
Telephone: +64 9 376 4936 .. Fax: +64 9 376 4997 .. E-mail: director@lam.org.nz