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.

Happy Easter to all my readers

John 20
1Early on the first day of the week, while it was still dark, Mary Magdalene went to the tomb and saw that the stone had been removed from the entrance. 2 So she came running to Simon Peter and the other disciple, the one Jesus loved, and said, “They have taken the Lord out of the tomb, and we don’t know where they have put him!”

3 So Peter and the other disciple started for the tomb. 4 Both were running, but the other disciple outran Peter and reached the tomb first. 5 He bent over and looked in at the strips of linen lying there but did not go in. 6 Then Simon Peter, who was behind him, arrived and went into the tomb. He saw the strips of linen lying there, 7 as well as the burial cloth that had been around Jesus’ head. The cloth was folded up by itself, separate from the linen. 8 Finally the other disciple, who had reached the tomb first, also went inside. He saw and believed. 9 (They still did not understand from Scripture that Jesus had to rise from the dead.)
10 Then the disciples went back to their homes, 11 but Mary stood outside the tomb crying. As she wept, she bent over to look into the tomb 12 and saw two angels in white, seated where Jesus’ body had been, one at the head and the other at the foot.

13 They asked her, “Woman, why are you crying?”

“They have taken my Lord away,” she said, “and I don’t know where they have put him.” 14 At this, she turned around and saw Jesus standing there, but she did not realize that it was Jesus.

15 “Woman,” he said, “why are you crying? Who is it you are looking for?”

Thinking he was the gardener, she said, “Sir, if you have carried him away, tell me where you have put him, and I will get him.”

16 Jesus said to her, “Mary.”

She turned toward him and cried out in Aramaic, “Rabboni!” (which means Teacher).

17 Jesus said, “Do not hold on to me, for I have not yet returned to the Father. Go instead to my brothers and tell them, ‘I am returning to my Father and your Father, to my God and your God.’”

18 Mary Magdalene went to the disciples with the news: “I have seen the Lord!” And she told them that he had said these things to her.

Stemedica Ischemic Tolerant Stem Cells Generate Significant Improvement In Ejection Fraction After Heart Attacks

Stemedica Cell Technologies, Inc is a biotechnology company that has made stem cells for transplantation for a variety of maladies. One of their latest inventions is called ischemic tolerant mesenchymal stem cells or itMSCs. Such an invention has made Stemedica one of the leaders in adult allogeneic stem cell manufacturing, research and development. Transplantation of itMSCs has produced significant improvements in the pumping ability of the left ventricle in patients who had experienced a heart attack. Data from this study was presented at the 26th American College of Cardiology (ACC) meeting in Chicago, on March 26, 2012. The presentation by Daniyar Jumaniyazov, MD, PhD and Nikolai Tankovich, MD, PhD, President and Chief Medical Officer of Stemedica revealed this data to the meeting attendees.

45 patients who had just experienced a heart attack were given angioplasty and the placement of coronary artery stents (percutaneous infusion). Then these patients were divided into a treatment and a control group. The treatment group received intravenous infusion of itMSCs that were developed by Stemedica on the seventh day after the heart attack. The control group received normal saline with no cells. At the end of three months, those in the treatment group showed an 11-point improvement in their left ventricle ejection fractions (the amount of blood pumped with each heart contraction) in comparison with the control group. These improvements returned the ejection fraction of the treated patients to normal levels. The control group only showed a level of improvement expected with standard of care, but their ejection fractions remained below normal.

There were other markers that were improved in the treated group in comparison to the control group. Patients in the itMSC-treated group had lower levels of C-reactive protein and brain natriuretic protein (BNP), both of which are indicators of inflammation. Surveys of patients in the treated group also improved in quality of life indicators. Magnetic Resonance Imaging (MRI) performed six days and again 30 days after the heart attack showed significant decreases in lesion size in the treated group, but no such improvements were observed in the control group. Patients in this study will be followed for one year.

Nabil Dib, MD, MSc, FACC, Director, Clinical Cardiovascular Cell Therapy & Associate Professor of Medicine at the University of California, San Diego noted, “Data from this early clinical trial are very promising. If these results continue as patients are followed longer term, and if they can be replicated in a larger clinical trial, then Stemedica’s ischemic tolerant allogeneic mesenchymal stem cells may well play an important role in the treatment of heart disease.”

Jackie See, MD, FACC, an interventional cardiologist who specializes in stem cell research in Fullerton, California, commented: “These are impressive results and provide a great deal of hope for patients with heart disease. Stents open up the narrowed blood vessels. With the addition of stem cells, we can potentially rescue some of the damaged myocardial cells, promote new blood vessel growth, decrease inflammation, and strengthen the damaged muscle. I can see a day in the near future when intravenous itMSC administration becomes part of the standard of care following an acute myocardial infarct.”

Dr. Tankovich raised a key point about the research, by stating, “This study highlights the importance of using allogeneic stem cells specifically manufactured to be effective in the toxic tissue environment following a heart attack. In vitro, we know that our itMSCs secrete more of the important healing factors in response to ischemia. Our cells also retain their ‘steminess’, remaining undifferentiated and potent throughout the manufacturing process. They also pass the most stringent tests for infectious disease, acute and chronic toxicity and tumorigenicity, and they are immune privileged. These are some of the advantages of using a well characterized, homogeneous population.”

This experiment used borrowed cells from a healthy donor that were expanded in the laboratory. Dr. See noted that the importance of used borrowed cells: “Results from a large multi-center study supported by the National Heart, Lung, and Blood Institute, presented at the ACC, showed that bone marrow derived stem cells taken from older, sicker patients were not very effective in improving heart function. This is understandable, because these stem cells no longer have the power to differentiate, migrate, engraft and secrete the factors that are necessary for wound healing. So the patients who most need the treatment do not have potent stem cells to accelerate the cardiac healing process.”

Dr. Tankovich further notes that providing enough stem cells for thousands of patients who could benefit from Stemedica’s itMSC treatment is not an issue. “With our advanced expansion techniques, with only four passages, from a single tissue donation, we can treat half a million patients.”

This placebo-controlled, blinded Phase II clinical trial was conducted according to ICH guidelines at the National Medical Research Center (NMRC) in Astana, Kazakhstan. The NMRC is Kazakhstan’s premier medical research institute and internationally known for initial assessment and treatment of returning NASA astronauts. Based upon the outcome of this trial, NMRC is planning a Phase III trial using Stemedica’s itMSCs for a larger population.

Stemedica is planning a parallel Phase II clinical trial in the United States and Switzerland. The U.S. based trial will take place under Stemedica’s existing IND for the itMSCs. Swissmedic has found Stemedica’s itMSCs acceptable for clinical trials from Phase I to Phase III.

Jonah Goldberg on Infanticide in the Journal of Medical Ethics

Conservative columnist Jonah Goldberg, who writes for National Review, has commented on a barbaric paper that was published in the Journal of Medical Ethics that advocates infanticide. The authors, Alberto Giubilini and Francesca Minerva, have argued that early infanticide is no different from abortion. Therefore, since abortion is, in their view, permissible, then infanticide should be too.

The authors have a point. A trip nine inches down the birth anal does not make someone a person. If the baby was not a person in utero, then a nine-inch trip does not possibly make it a person. Location is an exceedingly unworkable means for defining personhood. The same must be said for degree of dependence. The infant is now breathing on her own, but she is still dependent on her mother for feeding and attention. Otherwise, the baby will starve to death and fail to thrive. Therefore, defining personhood by means of degree of dependence is also unworkable. The infant is still completely dependent on others. In terms of size, there are also few differences between the in utero baby and the newly born baby. Also, how is an 18-pound baby more of a person than a 10-pound baby. Are babies who are bigger at birth more of a person than seven-pound babies? This question is ridiculous. So it comes down to development. However, the development that occurs outside the uterus in the first few months is slow and gradual. The baby acquires new abilities gradually and in a push-and-pull manner. The differences are small and difficult to perceive. Can a baby who can raise its head more of a person than one who cannot? Is a baby who can turn over more of a person than one who cannot? Obviously not. None of these criteria work. They are poor reasons to deny someone personhood.

The simple fact is that babies are human persons at different stages of their lives. Their human lives began at the end of fertilization and will end when they die. Intentionally killing them at any time is murder. If this were done to a 5-year old it would be murder. However, because the baby in the uterus cannot be seen, we call it “a mother’s choice.” It is simple murder, plain and simple, and now these authors want to extend this murder right to murder to those outside the mother’s womb. This is barbaric.

Goldberg writes that the authors eschewed the backlash they experienced because of the article, and they explained that this was an article to other bioethicists who have debated infanticide for some time. But this is exactly the problem To even entertain the murder of the most defenseless and innocent among us to nothing more than evil and it does not matter if it is being discussed by academics. It is still evil, and we should be ashamed that it is tolerated even in an academic setting.

Goldberg’s take on it is well worth reading.  Find it here.

Mesenchymal Stem Cell Treatment of Secondary Progressive Multiple Sclerosis: Phase 2a proof-of-concept study

Multiple sclerosis is a disease that results when the immune system attacks the myelin insulation that wraps and covers particular nerves.  It is, therefore, part of a larger group of diseases called “autoimmune diseases.”  Because multiple sclerosis involves nerves, it affects the brain, spinal cord, and some peripheral nerve as well.

Typically, multiple sclerosis (MS) affects women more than men, which is common for most autoimmune diseases.  It is most commonly diagnosed between ages 20 and 40, but can it show up in anyone at practically any age.  The main cause of the pathology of multiple sclerosis is immune system-mediated damage to the protective covering that surrounds some, though not all nerves, the  myelin sheath.  Myelin sheaths help nerves transmit their nerve impulses faster, and without it, nerve signals slow down or stop altogether.

Damage to the myelin sheath results from specific immune cells that recognize the myelin sheath as a foreign invader.  The attacks against the myelin sheath cause inflammation at the nerves.  Inflammation results from immune cell activities whereby activated immune cells secrete chemicals called “cytokines” that sound the alarm in the immune system.  These cytokines recruit other immune cells to the site of injury or infection and the cells make antibodies against the foreign substance and other cells gobble up the foreign substance and destroy it.  You can see why the nerves take such a beating during multiple sclerosis.

Why does this happen in the first place?  There is no clear answer to this question.  Clearly some people are more prone than others to develop multiple sclerosis.  Infection of the nerves by particular viruses that cause the immune system to recognize it as foreign is another possibility, and other blame environmental factors.

Over half the patients with multiple sclerosis have progressive disease characterized by accumulating disability, and there are no treatments for them. Several experiments have established the ability of mesenchymal stem cells to suppress the damaging effects of autoimmune disorders, and in acute and chronic animal models of multiple sclerosis mesenchymal stem cells have many beneficial effects.  A recent paper has reported attempts to determine the safety and efficacy of mesenchymal stem cells as a potential treatment for secondary progressive multiple sclerosis.  The paper is Connick, P., et al., “Autologous mesenchymal stem cells for the treatment of secondary progressive multiple sclerosis: an open-label phase 2a proof-of-concept study,” Lancet Neurology 11(2): 2012:159-6. Paper

For this research, Connick and his colleagues recruited people from East Anglia and north London that suffered from secondary progressive multiple sclerosis that affects the visual pathway.  Because the ability to see is relatively easy to determine with eye tests, this population was a prime set of candidates for this study.  Study subjects received intravenous infusions of their own bone-marrow-derived mesenchymal stem cells.  Safety and feasibility were two of the factors that were examined in this study.

Side effects were examined from 20 months before treatment until up to 10 months after the infusion. Also, the eyesight of the patients was ascertained by eye tests, but the nerves were directly tested for their ability to send nerve impulses.  Multiple sclerosis prevents nerves from being able to form and propagate proper nerve impulses, and if this treatment works, then it should improve the ability of the nerves to form nerve impulses.

In ten patients, no serious side effects were observed (rashes after the injection and so on).  However, an improvement in visual acuity was observed in almost all the patients.  The field of vision increased, as did the ability of the nerves to form nerve impulses.  Color vision and the structure of the retina were no affected, but the increase in vision was significant.

Thus, autologous mesenchymal stem cells were safely administered to patients with secondary progressive multiple sclerosis, and there is even some evidence of structural, functional, and physiological improvement after treatment.  These data suggest that mesenchymal stem cells possibly modulate the immune response in these patients and protect the nerves.  While these results are preliminary, they certainly warrant further investigation.