StemCells Inc. Announces the Commencement of Their Macular Degeneration Clinical Trial

Age-related macular degeneration or AMD is a disease of the retina (at the back of the eye) characterized by a loss of photoreceptors (rods and cones) from the central part of the retina (macula), where vision in the clearest. A degenerative retinal disease, AMD typically strikes adults in their 50s or early 60s, and insidiously progresses usually painlessly until it gradually destroys central vision. There are approximately 1.75 million Americans age 40 years and older with some form of AMD, and the disease continues to be the number one cause of irreversible vision loss among senior citizens in the United States with more than seven million at risk of developing AMD.

There are no cures for AMD, but laser treatments are available for some types of AMD. Laser photocoagulation can disperse fluid that has built up under the retina. Such AMD is called “wet” macular degeneration and only works in the treatment of 15/100 cases of AMD. Other treatments include injections of either Avastin, Macugen or Eylea into the eye to prevent the spread of blood vessels that crowd out photoreceptors.  Photodynamic therapy uses a drug called Visudyne that is injected into the arm and them activated by a laser one in the eye where it destroys meandering blood vessels that leak or proliferate across the retina.  Patients with “dry” macular degeneration, however, find themselves out of luck.

Into the breach comes a clinical study by StemCells Inc. to use their proprietary neural stem cell line to treat dry macular degeneration. This Phase I/II clinical trial has already enrolled and transplanted its first patient this week and more subjects will undoubtedly be enrolled later. This trial is designed to evaluate the safety and preliminary efficacy of StemCells Inc’s proprietary HuCNS-SC neural stem cell line as a treatment for dry AMD. The first patient in this clinical trial received their transplant at the Retina Foundation of the Southwest in Dallas, Texas, which is one of the leading independent vision research centers in the United States. Globally, AMD afflicts approximately 30 million people worldwide and is the leading cause of vision loss and blindness in people over 55 years of age.

In February 2012, StemCells Inc Company published preclinical data that clearly showed that HuCNS-SC cells protect host photoreceptors and preserve vision in the rats that are engineered to experience retinal degeneration. This rat strain (Royal College of Surgeons or RCS rats) are a very well-established animal model for retinal disease and has been used extensively to evaluate potential cell therapies. In these pre-clinical studies, the number of cone photoreceptors, which are responsible for central vision, did not decrease due to cell death, but instead remained constant over an extended period. These same rats that had HuCNS-SC cells transplanted into their retinas showed steady maintenance of their visual acuity and light sensitivity. In humans, degeneration of the cone photoreceptors accounts for the unique pattern of vision loss in dry AMD. These data were published in an international peer-reviewed journal known as the European Journal of Neuroscience.

“This trial signifies an exciting extension of our on-going clinical research with neural stem cells from disorders of the brain and spinal cord to now include the eye,” said Stephen Huhn, MD, FACS, FAAP, Vice President and Head of the CNS Program at StemCells, Inc. “Studies in the relevant animal model demonstrate that the Company’s neural stem cells preserve vision in animals that would otherwise go blind and support the therapeutic potential of the cells to halt retinal degeneration. Unlike others in the field, we are looking to intervene early in the course of the disease with the goal of preserving visual function before it is lost.”

David G. Birch, Ph.D., Chief Scientific and Executive Officer of the RFSW and Director of the Rose-Silverthorne Retinal Degenerations Laboratory and principal investigator of the study, added, “We are excited to be working with Stem Cells [Inc.} on this ground breaking clinical trial. There currently are no effective treatments for dry AMD, which is the most common form of the disease, and there is a clear need to explore novel therapeutic approaches.”

Blood Vessel-Making Stem Cells Reprogrammed into Heart Muscle Cells That Improve Heart Function After a Heart Attack

Douglas Losardo at Northwestern University, Chicago, IL has done some extremely innovative work with transplanting bone marrow stem cells into the heart of human heart attack patients. His clinical trials have shown that human heart attack patients that receive infusions of their own bone marrow stem cells, on the average, show improved heart function, abatement of symptoms and improved prognosis.

In particular, Losardo has used CD34+ stem cells from bone marrow. CD34 is a cell surface protein that marks blood cell-making stem cells. CD34+ stem cells have been intensely studied and can form blood vessels in addition to red and white blood cells. The formation of new blood vessels in a sick heart improves the delivery of oxygen and blood to the heart, which improves heart function and recovery after a heart attack. Additionally, the CD34+ stem cells release a host of molecules that help the heart recover and function better.

The downside of CD34+ stem cells, is that they show limited ability to differentiate into heart muscle cells, and also do not survive terribly well in the heart after a heart attack. Therefore, Losardo has been on the hunt for a better technique for healing sick hearts, and a recent paper from his laboratory with mice provides a proof-of-concept of using reprogramming to form cells that can be used for regenerative therapies for the heart.

In this paper, Losardo and his team used a bone marrow stem cell called and “EPC,” which is short for “endothelial progenitor cell.” Endothelial cells compose blood vessels and EPCs make blood vessels. EPC infusions into a heart after a heart attack can improve heart function, but only modestly.

The first author of this paper, Melissa A. Thal, and her colleagues from Losordo’s laboratory treated EPCs isolated from mouse bone marrow with a cocktail of chemicals to move their gene expression patterns away from an EPC-specific pattern to that of a heart muscle cell. Their chemical cocktail contained either 5-Azacytidine, which changes the epigenetic profile of cells, and valproic acid, another epigenetic modifier, or a G9a histone dimethyltransferase called BIX-01294, which is also an epigenetic modifier. After soaking their EPCs in these chemicals for 48 hours, Genomic expression studies showed that pluripotency genes were expressed in these cells, as were genes for heart muscle and blood vessels. When cultured under the right conditions, these reprogrammed EPCs also formed good heart muscle cells.

These results were so remarkable that Losardo and his team decided to test these reprogrammed cells in the hearts of mice that have just experienced a heart attack. Transplantations of EPCs, or reprogrammed (REPCs) definitively showed that mice that had experienced heart attacks and did not have any interventions continued to deteriorate. However, EPC transplantations slightly improved the functional characteristics of the heart and tended to arrest the degradation of the heart. However, mice that had received REPCs had almost twice the % of blood ejected from the heart, significant reduction in the size of the damaged area, much less blood left in the heart after each pumping cycle, and better heart muscle function. Tissue examinations of the hearts showed that the REPC-transplanted hearts had grown new heart muscle whereas the EPC-transplanted hearts did not.

Thus this paper shows that it is feasible to reprogram EPCs from bone marrow into heart muscle cells and that it is also feasible to use these cells to repair the heart after a heart attack.

There were no significant side effects seen in the laboratory animals with the REPC transplantations. There were no tumors, no funky heart rhythms, and no sign of immunological rejection. Further work in animals will hopefully lead to human clinical trials and maybe even a commercially available treatment for heart attacks that use your own bone marrow stem cells. While that is a long way off, it is a hope that we all share.