Posted on 07/10/2008 6:28:54 PM PDT by Coleus
The primary focus of the trial at this stage was to establish the procedure’s safety, said Langleben, director of the JGH’s Centre for Pulmonary Vascular Disease. The positive effect that was observed in both patients’ health was a bonus that astonished the scientific team. The doctors are not claiming a cure, but Langleben said the treatment appears to have halted the progress of the disease. Doctors observed an almost immediate drop in the pressure in the tiny arteries in the patients’ lungs by 10 to 15 per cent, “which is not insignificant,” he said. Moreover, the flow of the blood through the arteries did not increase, which is sometimes an undesirable reaction when resistance is reduced.
“Yes, this is still at the very, very early stage, but we have nothing else to offer patients,” Langleben said. “But to see something work so quickly and effectively is incredibly encouraging.” The first patient treated, Lucie Moison, now 45, has had the disease for 13 years and was on the waiting list for a lung transplant before she underwent the stem cell procedure a year ago. She said she felt no ill effects from the treatment, an injection of seven million stem cells, and almost immediately felt much better than she had in years. She even played a game of tennis. That initial burst of health lasted only a couple of weeks, but the mother of two continues to enjoy an improvement over her previous condition. The doctors describe her condition as stable, a major victory in a disease that is progressive and debilitating.
Three months ago, Yvan Depatis, 72, received 23 million stem cells and reported that he also felt a sudden sense of well-being upon treatment, which levelled off, but he is still in much better condition than he was. “If I walked 100 metres, I was done in,” he said. Despatis, an engineer, was working in Ethiopia when he started feeling unwell, his main complaint being shortness of breath. Throughout the stem cell experiment, the patients continue to receive conventional therapy, which primarily alleviates symptoms. Moison and Despatis wear portable devices that automatically deliver their medication via catheter to the heart.
The JGH team, led by Galipeau, built upon the work of Dr. Duncan Stewart, CEO of the Ottawa Health Research Institute. He invented a technique for genetically modifying the stem cells of rats, which he was able to cure of pulmonary hypertension. Trials involving two human patients in Toronto were also conducted, but using lower stem cell doses, said Galipeau, a leading researcher with the Stem Cell Network. The JGH team collected the stem cells from the patients’ white blood cells, Galipeau explained. The cells were processed in a special sealed laboratory in the JGH’s Lady Davis Institute for Medical Research, where staff could be observed cloaked from head to toe in outfits resembling space suits to ensure sterility. The shape of the cells was first changed by adding protein hormones. Then synthetic DNA was introduced into them. They were electrically shocked which had the effect of re-programming the cells to produce nitric oxide, something that they do not do naturally.
The modified cells were then put into a syringe and gradually administered over three days to the patients through the neck, in ever-larger doses, under very close monitoring. The cells lodged in the lung releasing the nitric oxide, which relaxes the arteries, thereby lowering the pressure, and may also stimulate the repair and regeneration of the blood vessels there, Galipeau said. Galipeau said there are a thousand studies going on around the world on the therapeutic potential of stem cells, but “genetically engineering the cells is unique [to this study].” Elsewhere, “they are just cleaned up, so to speak, not manipulated, before being injected.”
The ultimate goal, of course, Langleben said, is to find a treatment that will reverse the disease, or even cure it. This may be at least five years away. It will take time because of the rigorous standards set by Health Canada and the availability of funding, he said. The team has now submitted a funding proposal to the federal authorities to treat people who have had heart attacks with a similar procedure. “This is the tip of the iceberg,” Galipeau said of the treatment’s potential.
Moisan, 45, had been waiting for a lung transplant, but she has responded so well to the stem-cell therapy and other drugs that's she's no longer on the transplant list. "I think this therapy is very promising," she said. "I have high hopes." Pulmonary hypertension occurs when the blood vessels in the lungs constrict, much like a garden hose that kinks up. The pressure builds up and less blood circulates through the lungs to collect oxygen. There is no cure for the disease. Half of those patients with the most severe form live for only three to five years after diagnosis. At present, there are about 1,500 people suffering from pulmonary hypertension in Quebec.
The Jewish General is one of two sites in Canada - the other is in Toronto - to pioneer the therapy. But the Jewish General has gone a step farther, infusing patients with the greatest dose of stem cells to date, 23 million of them. In any experimental therapy, doctors proceed cautiously, first using only small doses to test whether a compound is safe, and gradually boost the dosage. But Jewish General doctors said they were stunned to discover that with a relatively small dose, the stem cells decreased pulmonary arterial resistance by 15 to 25 per cent.
"It was absolutely fabulous," said David Langleben, director of the Centre for Pulmonary Vascular Disease. Under the procedure, the patient's blood is skimmed for monocyte white cells, which are transferred to a sterile lab. The cells are genetically re-engineered to turn into endothelial progenitor cells. The enhanced cells are infused in the patient's lungs through a catheter. The cells bind to the walls of hair-thin arteries and release nitric oxide, a molecule that repairs and protects the vessels. Unfortunately, these cells live for only a few weeks, so a patient would probably have to undergo repeated treatments. But the therapy has the potential to represent a major advance in the treatment of the disease, Langleben said.
www.osiris.com - Osiris Therapeutics, Inc. Erica Elchin, 443-545-1834 or Media: Schwartz Communications Stacey Holifield or Andrew Law, 781-684-0770 Osiris@schwartz-pr.com Osiris Therapeutics, Inc. (NASDAQ:OSIR) today announced the treatment of the first patients in a new Phase II clinical trial evaluating Prochymal, a mesenchymal stem cell (MSC) therapy, for moderate to severe Chronic Obstructive Pulmonary Disease (COPD). This trial marks the sixth indication for which Prochymal has been advanced into Phase II or later-stage clinical trials. COPD, a form of lung disease characterized by limitation or obstruction of airflow in the airway, encompasses both emphysema and chronic bronchitis. COPD is the fourth leading cause of death in the U.S. with an estimated 12 million Americans diagnosed with the disease. COPD has no known cure, thus current therapeutic intervention is aimed at providing relief of symptoms. Preclinical and clinical data suggest that Prochymal's unique mechanism of action may provide a first-in-class treatment option with the ability to reverse the underlying disease.
"Our COPD program serves as another example of how quickly and efficiently we can now work towards developing this first-in-class stem cell therapy," said C. Randal Mills, Ph.D., President and Chief Executive Officer of Osiris Therapeutics. "With the early testing completed, the clinical development and regulatory pathways are significantly streamlined for future indications. This supports our strategy to seek initial approval for the world's first stem cell drug in relatively small underserved diseases, such as GvHD and resistant Crohn's disease, and promptly expand the technology to include blockbuster markets for which the technology also holds great promise." "Studies that we and others have conducted provide convincing evidence that MSCs have the potential to be effective in addressing selected lung diseases, including COPD," said Daniel Weiss, M.D., Ph.D., Associate Professor of Medicine at the University of Vermont College of Medicine and an expert in research using stem cells to treat lung diseases. "These mesenchymal stem cells are particularly suited for treating pulmonary disease due to their inherent trafficking pathway through the lungs when delivered intravenously and their ability to remain in the lungs when inflammatory molecules are present. With their demonstrated ability to both reduce inflammation and reverse tissue damage, we have reason for optimism about Prochymal's use in this devastating disease."
A recent Osiris study evaluating Prochymal as a treatment for myocardial infarction demonstrated a statistically significant improvement in lung function as compared to placebo. Specifically, patients treated with Prochymal showed a 17 point improvement in FEV(1) % predicted, a measure of pulmonary function, versus only a 6 point improvement in patients treated with placebo (p less than 0.05). Prochymal has also demonstrated clinical benefit in trials evaluating patients with inflammatory conditions including graft-versus-host disease (GvHD) and Crohn's disease, both of which are in Phase III programs and have Food and Drug Administration (FDA) Fast Track status.
"This landmark study is very exciting for the entire field and we are honored to have been able to enroll and treat the first patients," said Charles Fogarty, M.D., Medical Director of Spartanburg Medical Research. "We look forward to the results of this trial, which may have long-term implications for improvements in disease progression and remodeling of the lung."
About the Phase II Chronic Obstructive Pulmonary Disease Trial
The Phase II trial will evaluate the safety and efficacy of Prochymal in conjunction with standard of care for improving pulmonary function in patients with moderate to severe COPD. The clinical trial is a double-blind, placebo-controlled study conducted at multiple sites with a target enrollment of 60 patients. Patients will be randomized to either Prochymal or placebo at a 1:1 ratio. Pulmonary function tests, exercise capability, and quality of life are some of the measurements being used to detect potential improvements in subjects treated with Prochymal. In addition, exacerbations and hospitalizations due to COPD will be monitored for both safety and efficacy. Patients will be evaluated over the course of two years following initial Prochymal or placebo infusion.
About Prochymal
Prochymal is a preparation of mesenchymal stem cells specially formulated for intravenous infusion. The stem cells are obtained from the bone marrow of healthy adult donors. Prochymal is currently being evaluated in three, double-blind, placebo controlled Phase III studies, including steroid refractory GvHD, acute GvHD, and Crohn's disease. Prochymal has been granted Fast Track status by FDA for all three of these indications. Prochymal also obtained Orphan Drug status by FDA and the European Medicines Agency for GvHD. FDA established the Fast Track program to accelerate the development of drugs that show promise for treating life-threatening conditions. Orphan Drug designation provides incentives to companies that develop drugs for underserved patient populations. Prochymal is also being studied in Phase II trials for the treatment of acute myocardial infarction, type 1 diabetes, and COPD. Additionally, the Department of Defense recently awarded Osiris a $224.7 million contract to develop Prochymal for acute radiation syndrome.
About Osiris Therapeutics
Osiris Therapeutics, Inc. is a leading stem cell therapeutic company focused on developing and marketing products to treat medical conditions in the inflammatory, orthopedic and cardiovascular areas. Osiris currently markets and sells Osteocel(R) for regenerating bone in orthopedic indications. Prochymal(TM) is being evaluated in Phase III clinical trials for three indications, including acute and steroid refractory Graft versus Host Disease and also Crohn's disease, and is the only stem cell therapeutic currently designated by FDA as both an Orphan Drug and Fast Track product. Osiris also has partnered with Genzyme Corporation to develop Prochymal(TM) as a medical countermeasure to nuclear terrorism and other radiological emergencies. Prochymal is also being developed for the repair of heart tissue following a heart attack, the protection of pancreatic islet cells in patients with type 1 diabetes, and the repair of lung tissue in patients with chronic obstructive pulmonary disease. The Company's pipeline of internally developed biologic drug candidates under evaluation also includes Chondrogen(TM) for arthritis in the knee. Osiris is a fully integrated company, having developed capabilities in research, development, manufacturing, marketing and distribution of stem cell products. Osiris has developed an extensive intellectual property portfolio to protect the company's technology in the United States and a number of foreign countries including 47 U.S. and 253 foreign patents owned or licensed. More information can be found on the company's website, www.Osiris.com. (OSIR-G)
As described in the April 1st issue of the American Journal of Respiratory and Critical Care Medicine, Dr. Weiss of the University of Vermont College of Medicine Burlington, and colleagues obtained human cord blood from normal deliveries, and extracted and cultured mesenchymal stem cells in specialized airway growth media or with specific growth factors. These cultured cells could be induced to differentially express markers of the airway epithelial phenotype including Clara cell secretory protein, cystic fibrosis transmembrane conductance regulator (CFTR), and surfactant protein C.
Systemic administration of the cultured cells to immunotolerant mice led to some localization in the airway and alveolar epithelium. In both regions, the cells acquired cytokeratin expression. Moreover, those that appeared to have engrafted as airway epithelium showed human CFTR expression. The investigators observe that their approach appears to be comparable to using stem cells from adult bone marrow. "With further research," concluded Dr. Weiss, "we hope these cells could be utilized to repair damaged lungs in diseases such as cystic fibrosis and emphysema."
Am J Respir Crit Care Med 2008;177:701-711.
This is fabulous! I hope they go far in their findings of the great uses for adult stem cells.
I wonder if anyone has noticed the irony that this is done at a Jewish hospital, but you never hear of this sort of thing at a Muslim hospital.
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