In the News

Heather Natola, Ph.D.

Heather Natola successfully defended her PhD thesis on Tuesday, October 3rd!

Make sure to congratulate her when you see her.

Nicole Scott-Hewett, a recent graduate of the GDSC program will be joining Beth Steven's laboratory at the Boston Children's Hospital F.M. Kirby Neurobiology Center. There Nicole will be involved in projects related to understanding mechanisms of complement and microglia-mediated pruning in development and in disease models. With her paper in this month's issue of PLoS Biology on lysosomal dysfunction, Nicole leaves us with a fanfare. We wish her all the best for her new beginnings in Boston!

Department of Biomedical Genetics researchers believe they have identified a new means of treating some of the most severe genetic diseases of childhood, according to a new study in PLOS Biology. The diseases, called lysosomal storage disorders (LSDs), are caused by disruptions in the functioning of the stomach of the cell, known as the lysosome. LSDs include Krabbe disease, Gaucher disease , metachromatic leukodystrophy and about 40 related conditions. In their most aggressive forms, they cause death of affected children within a few years after birth.

The research was spear-headed by Nicole Scott-Hewett and Chris Folts, two recent graduates of the program in Genetics, Development and Stem Cells. Led by the article's corresponding author Mark Noble, Ph.D., the team discovered for the first time how specific toxic waste products that accumulate in LSDs cause multiple dysfunctions in affected cells. They also found that several drugs already approved for other uses have the unexpected ability of overcoming the cellular toxic build-up, providing new opportunities for treatment. Key to this discovery was the finding that these drugs can help restore normal acidification of the lysosome.

In a mouse model of Krabbe disease (one of the most severe LSDs), Drs. Folts and Scott-Hewett found that their lead study drug, colforsin, increased survival as effectively as in studies where disease-causing mutations were corrected by gene therapy. Colforsin is approved in Japan to treat cardiac disease, which provides information to investigators about its use in humans.

Increased survival in mice occurred even though treatment was started later than is necessary for gene therapy. The research treatment also decreased damage to the brain and improved the quality of life in the diseased mice. All of these outcomes are critical goals in the treatment of children with Krabbe disease or related illnesses, said Noble, who is the Martha M. Freeman, M.D., Professor in Biomedical Genetics at URMC.

"One of the great challenges in these diseases is that they are both rare and come in many different varieties, and advances have tended to focus on single diseases," Noble said. "In contrast, our findings suggest our treatments will be relevant to multiple disorders. Also, we saw benefits of our treatment even without needing to correct the underlying genetic defects. That gives us great hope that we could combine our treatments with other candidate approaches to gain additional benefits."

If the results can be translated into humans, Noble said, the repurposed drugs might improve the quality of life for afflicted children while more difficult experimental genetic treatments are pursued. The complete study can be found at: PLoS Biology

Researchers in Rochester have developed a new cell therapy that could treat Parkinson’s disease, a neurological disorder which affects motor function. The study from the University of Rochester Medical Center suggests this new approach could not only halt progression of the disease, but also reverse its impact on the brain.

Now, researchers have found a way to use supporter cells known as astrocytes to spur wider recovery throughout the brain. So we can think of them as a work crew that delivers multiple tools at the same time, each of which can target a different cell population, says lead author Chris Proschel.

Proschel says they were careful to begin their treatment only after their lab mice had developed signs of Parkinson’s disease. He says this delay is important because it mimics the way therapies are actually used in humans, where damage has occurred and symptoms have presented before any treatment is carried out.

A recent study shows that, when properly manipulated, a population of support cells found in the brain called astrocytes could provide a new and promising approach to treat Parkinson's disease. These findings, which were made using an animal model of the disease, demonstrate that a single therapy could simultaneously repair the multiple types of neurological damage caused by Parkinson's, providing an overall benefit that has not been achieved in other approaches.

One of the central challenges in Parkinson's disease is that many different cell types are damaged, each of which is of potential importance, said Chris Proschel, Ph.D., an assistant professor of Biomedical Genetics at the University of Rochester Medical Center (URMC) and lead author of the study which appears today in the European journal EMBO Molecular Medicine. However, while we know that the collective loss of these cells contributes to the symptoms of the disease, much of the current research is focused on the recovery of only one cell type.

Above is Part 3 of ISSCR's video blogs from the 2013 ISSCR annual meeting. This video introduces the fascinating research in cell-based CNS repair done by Dr. Christoph Pröschel.

Dr. Pröschel’s most recent work has focused on using human glial progenitor cells to repair damage to the CNS caused by spinal cord injury. In a 2011 study published in PLoS One, Dr. Pröschel and colleagues describe how human glial precursors were able to restore motor function to spinal cord-injured rats. In our interview, Dr. Pröschel explains the difference between replacement and repair in cell-based regenerative medicine, a theme that fellow spinal cord injury researcher Dr. Aileen Anderson of UC Irvine also frequently touches on. In our video, Dr. Pröschel also has some remarks about direct lineage reprogramming.