Clinical Trial shows that Stem Cell Injections In Lou Gehrig’s Disease Can Be Given Safely

The journal Stem Cells has released an online version of a paper ahead of the print version that describes an important experiment in the treatment of amyotrophic lateral sclerosis (ALS), otherwise known as Lou Gehring’s disease. This paper describes an experiment that resulted from collaboration between the University of Michigan, Emory University and NeuralStem, Inc., which sponsored the study.

In this clinical trial, 12 patients were transplanted with spinal cord stem cells. All transplantations were done at Emory University. The early results of this trial show that spinal stem cells can be safely delivered into the spinal cords of ALS patients. This study might certainly open the door to further research on stem cell-based treatments for ALS.

All 12 patients had ALS and none experienced any long-term complications from this stem cell transplantation procedure. Additionally, none of the patients showed any signs of rejecting the implanted cells. Because inflammation in the spinal cord accelerates the progression of the disease, there were concerns that the implantation could increase the disease in these patients. However, in the months following the surgery that was used to inject the stem cells, none of the patients showed evidence that their ALS progression was accelerating.

Eva Feldman, M.D., Ph.D. is the principal investigator at the University of Michigan Medical School for this trial and serves as a consultant to NeuralStem. She is also the director of the A. Alfred Taubman Medical Research Institute and the U-M Health System’s ALS Clinic. Dr. Feldman stated, “This important publication reinforces our belief that we have demonstrated a safe, reproducible and robust route of administration into the spine for these spinal cord neural stem cells. The publication covers data up to 18 months out from the original surgery. However, we must be cautious in interpreting this data, as this trial was neither designed nor statistically powered to study efficacy.”

The trial began in January 2010 at Emory University. The first 12 patients received neural stem cell transplants in the lumbar, or lower, region of the spinal cord. After reviewing safety data from these patients, the Food and Drug Administration granted approval for the trial to advance to the final two groups of patients (three in each group), all of whom will be transplanted in the cervical, or upper, region of the spinal cord.

Nicholas Boulis, M.D., associate professor of neurosurgery at Emory School of Medicine, performs the surgery that implant the neural stem cells. Boulis also developed the device he used inject the stem cells into the spinal cord. This same device received a notice of patent allowance from U.S. Patent and Trademark Office in October. NeuralStem has purchased an exclusive license to this technology. Boulis trained in neurosurgery at University of Michigan and collaborated on research with Feldman during his seven years of residency. He holds an adjunct associate professor of neurology position at University of Michigan and is one of the Taubman Scholars at the U-M Taubman Institute.

This clinical trial is one of the first U.S. clinical trials of stem cell injections into the spinal cord for the treatment of ALS. NeuralStem, Inc., a Maryland-based company, is funding the clinical trial and has also provided the human neural stem cells for transplantation. NeuralStem’s cells have the ability to mature into various types of cells in the nervous system, including the motor neurons that are specifically lost in ALS. However, scientists say the goal of stem cell transplantation is not to generate new motor neurons, but to protect the still-functioning motor neurons by nurturing them with the stem cells, and therefore, potentially slowing the progression of the disease.

Arsenic turns stem cells into cancer-causing cells

National Institutes of Health (NIH) scientists have made an interesting discovery with regard to arsenic and its effects on stem cells. Arsenic can turn normal stem cells into cancerous cells that grow uncontrollably and cause tumors. Arsenic is a common pollutant of drinking water in some parts of the world, and has previously been shown to be a cancer-causing chemical (carcinogen). Interestingly, cancer is probably a stem cell-based disease. Therefore, arsenic seems to convert the healers of our bodies from profitable entities to the makers of tumors.

Michael Waalkes, who heads a research team at the National Toxicology Program Laboratory, National Institute of Environmental Health Sciences (which is part of the NIH), has shown previously that treatment of normal cells with arsenic causes them to become cancerous. However, the present study shows that when these converted cancer cells are placed in proximity to normal stem cells, but not in contact with them, the normal stem cells quickly acquire the characteristics of cancer stem cells. Thus malignant cells can send molecular signals that transfer the message to grow uncontrollably to other cells. In fact, the placement of a semi-permeable membrane, between the cancer cells and the normal stem cells does not prevent the transformation from occurring. This demonstrates that small molecules that are made by the arsenic-transformed cell can are small enough to pass through the membrane and signal to the normal stem cells to turn them into cancer stem cells.

“This paper shows a different and unique way that cancers can expand by recruiting nearby normal stem cells and creating an overabundance of cancer stem cells,” said Waalkes. “The recruitment of normal stem cells into cancer stem cells could have broad implications for the carcinogenic process in general, including tumor growth and metastases.”

Waalkes’ lab started working with stem cells about five years ago. The researchers used a prostate stem cell line, not embryonic stem cells. “Using stem cells to answer questions about disease is an important new growing area of research. Stem cells help to explain a lot about carcinogenesis, and it is highly likely that stem cells are contributing factors to other chronic diseases,” Waalkes said.

Stem cells are unique in the body. They stay around for a long time and are capable of dividing and renewing themselves. “Most cancers take 30 or 40 years to develop,” said Linda Birnbaum, Ph.D., director of NIEHS and NTP. “It makes sense that stem cells may play a role in the developmental basis of adult disease. We know that exposures to toxicants during development and growth can lead to diseases later in life.”

Next, Waalkes’ group will look to see if this finding is unique to arsenic or if other organic and inorganic carcinogens also show these effects on normal stem cells.

This paper reveals an extremely important aspect of arsenic carcinogenesis. Additionally it may explain why arsenic often causes multiple tumors of many types that form on the skin or inside the body. The paper is online in Environmental Health Perspectives.