Taubman Science
The Taubman Institute’s mission is to fund groundbreaking research in medical science, in an attempt to understand the genesis of disease and to develop innovative approaches to treatment and cure.
Here are some of the latest research findings to come out of Taubman-supported laboratories at the University of Michigan.
The first stem cell trial for ALS treatment wins FDA approval
New therapy that U-M neurologist helped develop will undergo Phase I trial at Emory University
U.S. Food and Drug Administration gave the green light Friday for a clinical trial of a new stem cell treatment for amyotrophic lateral sclerosis (ALS). University Michigan neurologist, Eva Feldman, M.D., Ph.D., will be the overall principal investigator for the first human clinical trial of a stem cell treatment for ALS, a fatal neurodegenerative disease.
The FDA approved an Investigational New Drug application from Neuralstem, Inc., a Rockville, Md.-based biotech company, to test the safety of a treatment in which patients will receive injections of the company’s patented neural stem cells at multiple sites along the spinal cord.
Director of the U-M ALS Clinic and the Director of the Taubman Institute, Feldman worked with a team of neurologists and with Neuralstem Inc. to develop the protocol for delivering the stem cells into the spinal cord of patients.
The Phase 1 trial to determine the safety of the treatment is expected to take place exclusively at Emory University in Atlanta, Ga., subject to approval by its Internal Review Board.
“We are very excited about this clinical trial,” said Feldman, the DeJong Professor of Neurology at the U-M Medical School. “This is a major stride forward in what still could be a long road to a new and improved treatment for ALS.
“ALS is a terrible disease that ultimately kills by paralysis. In work with animals, these spinal cord stem cells both protected at-risk motor neurons and made connections to the neurons controlling muscles. We don’t want to raise expectations unduly, but we believe these stem cells could produce similar results in patients with ALS,” Feldman said.
ALS, also known as Lou Gehrig’s disease, affects about 30,000 Americans. It progressively destroys the neurons that control voluntary muscles, leaving affected people unable to move or speak. There are no known treatments for the disease that slow its progression.
The trial will ultimately consist of 18 ALS patients with varying degrees of the disease. The FDA has approved the first stage of the trial, which consists of 12 patients who will receive five-to-ten stem cell injections in the lumbar area of the spinal cord. The patients will be examined at regular intervals post-surgery, with final review of the data to come about 24 months later.
Jonathan Glass, M.D., director of the Emory Neuromuscular Laboratory, is expected to be the site principal investigator for the trial.
Individuals interested in further information on the trial should contact Emory Health Connection, 404-778-7777, or 1-800 75EMORY, or go to www.neurology.emory.edu/als
Institutional review boards at U-M and Emory University must first approve the protocol.
If Phase I results are favorable, the treatment will need to prove effective in Phase II and III trials and win final FDA approval before it can be available for public use.
Funding: Neuralstem, Inc. plans to conduct and fund the Phase I trial of its patented technology.
Patents/conflict disclosures: Dr. Feldman has no financial interest in or financial arrangement with Neuralstem.
Other coverage:
Triglycerides may provide early warning for diabetes nerve loss
Monitoring the amount of fat in the blood of patients with diabetes might be just as important as tracking their blood sugar, according to a study by Taubman Scholar Eva L. Feldman, M.D., Ph.D.
Triglycerides – a form of fat measured in routine blood tests – may allow doctors for the first time to predict which patients with diabetes are more likely to develop serious and painful nerve damage.
Neuropathy affects 60 percent of people with diabetes, causing often severe numbness and pain. Until now, medical scientists did not have a useful test to predict which patients were likely to develop this complication and need more aggressive treatment.
In this study, funded in part by the Taubman Institute, Feldman’s laboratory analyzed data from 427 diabetes patients with neuropathy.
The data revealed that patients with elevated triglycerides were significantly more likely to experience worsening neuropathy over a period of one year.
Other factors, such as high levels of other fats in the blood or glucose, did not turn out to be significant.
With a readily available predictor for nerve damage, doctors and patients can take pro-active steps when interventions can do some good, says Feldman, senior author of the study and the Director of the Taubman Institute.
“These results set the stage for clinicians to be able to address lowering fat counts with their diabetes patients as vigilantly as they pursue glucose control,” Feldman says. “Aggressive treatment can be very beneficial to patients in terms of their neuropathy.”
People can reduce blood triglyceride levels with the same measures that reduce cholesterol levels: avoiding harmful fats in the diet and exercising regularly.
This study appears in the online journal Diabetes. It will appear in print in the July issue.
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Blocking inflammation receptor kills breast cancer stem cells, U-M study finds
Max S. Wicha, M.D., Distinguished Professor of Oncology and director of the U-M Comprehensive Cancer Center
Scientists at the University of Michigan Comprehensive Cancer Center have uncovered an important link between inflammation and breast cancer stem cells that suggests a new way to target cells that are resistant to current treatments.
The researchers identified a receptor, CXCR1, on the cancer stem cells which triggers growth of stem cells in response to inflammation and tissue damage. A drug originally developed to prevent organ transplant rejection blocks this receptor, killing breast cancer stem cells and preventing their metastasis in mice, according to the study.
Cancer stem cells, the small number of cells that fuel a tumor’s growth, are believed to be resistant to current chemotherapies and radiation treatment, which researchers say may be the reason cancer so often returns after treatment.
“Developing treatments to effectively target the cancer stem cell population is essential for improving outcomes. This work suggests a new strategy to target cancer stem cells that can be readily translated into the clinic,” says senior study author Max S. Wicha, M.D., Distinguished Professor of Oncology and director of the U-M Comprehensive Cancer Center. Wicha was part of the team that first identified stem cells in breast cancer.
Results of the current study appear online Jan. 4 in the Journal of Clinical Investigation and will appear in the journal’s February print issue.
CXCR1 is a receptor for Interleukin-8, or IL-8, a protein produced during chronic inflammation and tissue injury. When tumors are exposed to chemotherapy, the dying cells produce IL-8, which stimulates cancer stem cells to replicate. Addition of the drug repertaxin to chemotherapy specifically targets and kills breast cancer stem cells by blocking CXCR1.
Mice treated with repertaxin or the combination of repertaxin and chemotherapy had dramatically fewer cancer stem cells than those treated with chemotherapy alone. In addition, repertaxin-treated mice developed significantly fewer metastases than mice treated with chemotherapy alone.
“These studies suggest that important links between inflammation, tissue damage and breast cancer may be mediated by cancer stem cells. Furthermore, anti-inflammatory drugs such as repertaxin may provide a means of blocking these interactions, thereby targeting breast cancer stem cells,” Wicha says.
Repertaxin has been tested in early phase clinical trials to prevent rejection after organ transplantation. In these studies, side effects seem to be minimal. There are no reports of using repertaxin to treat cancer.
For more information, go to www.cancer.med.umich.edu/news/breast_cancer_stem_cell_treatment10.shtml
Note to patients: This work was done in cell cultures and mice. Repertaxin is not available to patients at this time and no clinical trials are yet planned.
Breast cancer statisitics: 194,280 Americans will be diagnosed with breast cancer this year and 40,610 will die from the disease, according to the American Cancer Society.
Additional authors: Christophe Ginestier, Suling Liu, Mark Diebel, Hasan Korkaya, Ming Luo, Marty Brown, Jun-Lin Guan, Gabriela Dontu, all from U-M; and Julien Wicinski, Olivier Cabaud, Emmanuelle Charafe-Jauffret, Daniel Birnbaum, all from Universite de la Mediterranee, Marseille, France
Funding: National Institutes of Health, Breast Cancer Foundation, Taubman Institute, Department of Defense, Inserm, Institut Paoli-Calmettes, Institut National du Cancer, Ligue Nationale Contre le Cancer
Disclosure: The University of Michigan has filed for patent protection on this technology, and is currently looking for a commercialization partner to help bring the technology to market.
Reference: Journal of Clinical Investigation, Vol. 120, No. 2, February 2010; doi:10.1172/JCI39397
Resources:
U-M Cancer AnswerLine, 800-865-1125
U-M Comprehensive Cancer Center, www.mcancer.org
