Crohn’s disease trial uses stem cells taken from placentas

A placenta provides a home for a baby, keeps the mom's body from rejecting it and soon could help patients suffering from Crohn's disease, multiple sclerosis and stroke, officials said Wednesday at the World Stem Cell Summit.

Patients with Crohn's disease, which inflames the digestive tract, have shown improvement with placenta-derived stem cells, which are adult stem cells, said Steven A. Fischkoff, vice president, clinical and medical affairs at Celgene Cellular Therapeutics.

The New Jersey-based biotech company is moving into the second phase of a Food and Drug Administration-approved clinical trial that uses placenta stem cells in patients with Chron's disease. It also is beginning a trial with patients suffering from multiple sclerosis.

Soon it is planning to seek FDA approval to use the placenta stem cells in patients suffering from stroke, based on the work of a neurology researcher at Henry Ford Health System.
"This could potentially affect a lot of people … and if we are successful, we will reduce the chances that people will have to go into nursing homes or rely on someone for care," Fischkoff said during the last day of the World Stem Cell Summit. "What really terrorizes people with a lot of these diseases is that they lose their independence."

The World Stem Cell Summit, a global gathering of researchers and leaders in Detroit, wrapped up its sixth annual event Wednesday at the Detroit Marriott. The three-day event, which was preceded by a free day at the Detroit Science Center, brought in nearly 1,000 scientists, industry leaders and advocates.

Attendance was down slightly from last year's summit, but this year's was the best ever staged, said Bernard Siegel, executive director of the Genetics Policy Institute, which presents the summit.
Prior to the summit, University of Michigan announced it had created its first embryonic stem cell line.
During the summit, an announcement was made about the new Oakland University William Beaumont Institute for Stem Cell and Regenerative Medicine. Scientists and companies from around the globe showcased their research and innovations.

"There is a fight to be fought and a war to be won," said Grant Albrecht, a patient advocate living with Transverse Myelitis, a neurological disorder.

The stem cell community has to stay focused on keeping the research on track, Siegel said, and that means mobilizing support for federal funding of embryonic stem cell research, which is currently in jeopardy with a lawsuit that seeks to ban it.

"Funding in the U.S. for embryonic stem cell research is on a knife's edge," Siegel said. "It can go either way. We can go back … or we can move into the 21st century. If you take the tool out of the tool kit, you delay the research to cures. It is akin to crushing hope."


From The Detroit News: http://www.detnews.com/article/20101006/METRO/10060437/1409/metro#ixzz12ZTjxTwz

From Wall Street Journal - Unraveling Crohn's Genetic Trail

From April 27, Wall Street Journal In the search for the causes of irritable-bowel conditions like Crohn's disease, doctors had long focused on diet. But studies have repeatedly failed to show that foods are to blame.

Now, researchers are focusing on genetic mutations linked to these conditions. The hope: to develop a therapy that fixes those mutations in order to actually cure diseases like Crohn's and ulcerative colitis, rather than just treat the symptoms.

For more than 15 years, Warren Strober has been studying these diseases at the National Institute of Allergy and Infectious Diseases in Bethesda, Md. He and other scientists have shown that dozens of genes are linked to Crohn's and ulcerative colitis.


Dr. Strober's current work centers on developing a stem-cell-based therapy to correct one particular gene mutation for Crohn's. But the wide variety of mutations means that there could eventually be a number of different treatments that target patients based on their genetic profiles, a strategy known as "personalized medicine."

In irritable-bowel conditions, the immune system attacks harmless bacteria normally found in the gut. This response leads to inflammation of different parts of the digestive tract, which in turn can cause pain, fissures, abscesses and obstruction.

In Crohn's, the walls of the digestive tract become inflamed, and any part—from the mouth through the large intestine—can be affected. With ulcerative colitis, only the lining of the bowel is damaged. Together, the conditions affect about 1% of the U.S. population.

People with Crohn's can suffer from chronic diarrhea, abdominal pain, fever, fatigue and sometimes rectal bleeding. They may also have problems absorbing an adequate amount of nutrients from food, particularly if too much of the intestine is removed. The disease can stunt the growth of children.



Treatments have improved in recent years and now include powerful, injectable biologic medicines that reduce inflammation, such as Johnson & Johnson's Remicade and Abbott Laboratories' Humira.



But these therapies aren't cures, and not everyone responds to them. In severe cases, patients must undergo surgery—sometimes multiple surgeries—to remove parts of the bowel or colon that are blocked. For Crohn's, in particular, because it can develop in any part of the gut, inflammation can recur even after surgery in a different segment of the digestive tract. Within 10 years after surgery, 80% to 90% of Crohn's patients will have a relapse, according to researchers.

In their search for a cure, Dr. Strober says he and his colleague, Ivan Fuss, are "bounding ahead" on research in mice that aims to fix a genetic mutation called NOD2 associated with Crohn's. The idea would be to have the body repair itself by growing the corrected gene using so-called induced pluripotent stem cells.

Stem cells are those that can develop into different types of specialized cells, like heart or muscle cells, and are mostly found in embryos. Induced pluripotent stem cells, or iPS cells, are made by taking adult specialized cells and turning back the clock, engineering them to an earlier stage where they can reproduce again.

Dr. Strober's team has already figured out how to take cells from the intestine and convert them into iPS cells. Now, they are working on fixing the genetic defect in the iPS cells before testing the therapy in animals.

First, they take segments of human DNA that contain the NOD2 gene mutation and break the DNA apart. Then, like a puzzle, they reassemble the DNA except for the one broken piece—the gene mutation. That piece is replaced with a new, corrected piece of DNA.

After the gene mutation is corrected, the completed iPS cell will be administered into the bone marrow of mice with Crohn's disease, where the new intestinal cells that develop should be fully functioning again. They plan to begin testing mice later this year.

The biggest challenge with this type of "integrated science" approach—one that combines genetic information, physical symptoms and biology—is narrowing down which genetic combinations are critical to which patients, according to Stephan Targan, director of the division of gastroenterology and the institute for inflammatory bowel immunobiology at Cedars-Sinai Medical Center in Los Angeles.

Dr. Strober and others are also looking at different genetic and molecular pathways that could lead to better understanding and treatments for Crohn's and ulcerative colitis.  Other researchers are examining how genetic mutations affect the type of bacteria that are found in the digestive tract. Greater presence of certain types of bacteria may be more likely to trigger an immune response. Still another area of research focuses on understanding how individuals' genetic makeup can make them susceptible to certain other Crohn's triggers, such as stress, smoking and the use of nonsteroidal anti-inflammatory painkillers.

Celgene PDA-001 Stem Cell Therapy is Safe Treatment for Crohn's Disease

According to Business Week, Celgene Corp. reported a successful safety trial of a placenta-derived stem cell therapy as a treatment for Crohn's disease. Celgene said the early stage trial showed PDA-001 is safe. It also showed signs of effectiveness, and Celgene is planning to begin studying the therapy as a treatment for several other diseases.

The study involved 12 patients with moderate to severe Crohn's disease who had not been helped by at least one previous treatment. They were given two infusions of Celgene's PDA-001 at one week apart, at one of two doses. Celgene said PDA-001 is derived from normal, full-term human placental tissue. The treatment is being studied by the company's Celgene Cellular Therapeutics unit.

Crohn's disease is marked by chronic inflammation of the gastrointestinal tract. Almost 1 million people in the U.S. suffer from the disease, according to Celgene.

Anyone involved in the Celegene study for Crohn's?

Crohn's Disease Flare Up

Maybe it is my diet, maybe it is stress, but I sure feel like I am entering into a flare up. Not as much stomach pain, but I feel like I spend so much time in the bathroom. Usually by now I've pulled out of it, and I haven't been on any medicine for the past couple of years, but it is starting to look like I need to find a good gastro in South Florida. Anyone have any recommendations on either pulling out of a Crohn's Disease Flare up or a good gastroenterologist in the Boca Raton area?

Living with Crohn's - Vitamin D Deficeincy Linked to Crohn's

Chronies - Are you getting  your Vitamin D?

MONTREAL, Jan. 30 (UPI) -- Canadian researchers say vitamin D can counter the effects of Crohn's disease. Researchers at Montreal's McGill University Health Center and University of Montreal found vitamin D acts directly on the beta defensin 2 gene, which encodes an anti-microbial peptide and the NOD2 gene that alerts cells to the presence of invading microbes.

Both Beta-defensin and NOD2 have been linked to Crohn's disease -- an autoimmune disorder in which a defect in innate immune handling of intestinal bacteria leads to inflammatory bowel disease.

"Our data suggests, for the first time, that vitamin D deficiency can contribute to Crohn's disease," study leader Dr. John White of McGill says in a statement.

White suggests siblings of patients with Crohn's disease who have not as yet developed the disease make sure they are vitamin D sufficient. "It's something that's easy to do, because they can simply go to a pharmacy and buy vitamin D supplements," he says.

The study findings are published in the Journal of Biological Chemistry.

New clinical Trial for Crohn's Disease

Robarts Clinical Trials at The University of Western Ontario in London, Canada, has been awarded a 4.7 million dollar grant to conduct a randomized controlled trial evaluating treatment options for Crohn's disease. The outcome is expected to lead to a more streamlined treatment path and better disease management for patients. Abbott, the global health care company, has provided a grant to complete research for the REACT (Randomized Evaluation of an Algorithm for Crohn's Treatment) study.


Crohn's disease is a chronic inflammatory disorder that is characterized by symptoms of diarrhea, abdominal pain and gastrointestinal bleeding. It typically effects younger people and can result in serious complications such as bowel obstruction. Although conventional anti-inflammatory treatments such as prednisone improve symptoms, they are associated with important side effects and are only partially effective. Many patients require surgery to treat the disease.

The REACT study will be carried out at 40 gastroenterology practices in Canada and Belgium. The sites will be randomly assigned to treat patients with Crohn's disease to either a conventional management strategy featuring gradual escalation of drug therapy or a newer paradigm that features early use of combined immunosuppression with a tumor necrosis factor alpha blocking drug and an anti-metabolite.

"This trial builds on the results of recent studies that suggest use of combined therapy early in the course of treatment yields superior long-term results," says Dr. Brian Feagan, the lead investigator for the study. "We are excited about this project since it is the first large-scale, community-based evaluation of this approach. We expect that patients treated with combination therapy will be more likely to enter remission and rates of hospitalization and health-care utilization will be reduced." Dr. Feagan is the Director of Robarts Clinical Trials and a professor in the Department of Medicine at Western's Schulich School of Medicine & Dentistry.