Research on the use of stem cells to treat neurological disease bolstered with $4.5 million in grants

By Tom Rickey

The laboratory headed by Steven Goldman, M.D., Ph.D., chair of the Department of Neurology at the University of Rochester Medical Center, has received $4.5 million in new funding to further its efforts to use stem cells and related molecules to treat several disorders for which there are currently no cures.

The new funding, which will support work in the laboratory for the next three to five years, comes from a mix of private and government sources, including the National Multiple Sclerosis Society, the CDHI Foundation for Huntington’s disease research, Biogen Idec and the National Institutes of Health.

Goldman’s research is at the forefront of attempts to harness the promise of stem cells to benefit patients who suffer from neurological diseases.

Two newly funded projects focus on the molecular events involved in the repair of myelin. In one project, Goldman’s team is working on ways to use stem cells derived from human skin cells as the source of cells to ultimately treat patients with multiple sclerosis. Goldman’s lab has deciphered many of the molecular steps necessary to develop stem cells derived from skin cells into an oligodendrocyte, the type of brain cell that creates myelin in the brain. Now, the team has been awarded $770,000 from the National Multiple Sclerosis Society to better define how these cells respond to demyelination in the brain, as occurs in MS, so that scientists can better predict the effects of transplanting the cells into patients.

In a related project funded by a $1.7 million grant from the National Institutes of Health, Goldman’s team will establish mice whose brains contain some human oligodendrocytes and human myelin in order to recreate in these mice the type of damage that occurs in the brains of MS patients. By analyzing what happens to the cells at the molecular level, the team hopes to learn how to regenerate new myelin from progenitor cells that reside in the brain.

A closely related project, for which the lab was granted $670,000 by Biogen Idec, focuses on using these mice with human myelin to study the progression of a rare brain disease, progressive multifocal leukoencephalopathy, which can affect people whose immune systems have been suppressed with medication. The virus is found only in the human brain, posing a problem for scientists who would like to study it thoroughly. But by seeding the brains of mice from birth with human myelin, Martha Windrem, Ph.D., research assistant professor in the Goldman laboratory has established mice that can be infected by the virus that causes the illness, opening up new possibilities to learn about the disorder.

In a fourth project, supported with a $1.34 million grant by the CHDI Foundation, the team will explore the use of brain cells known as astrocytes to improve the condition of mice with Huntington’s disease. The goal is to prevent the death of a type of cell, known as a medium spiny neuron, which degenerates and dies in patients with the disease. The new work focuses on using astrocytes derived from stem cells to change the local brain environment in patients with Huntington’s disease, a necessary step to stop the disease in people.

The studies on myelin repair are closely linked to the lab’s research on a group of fatal children’s disorders known as pediatric leukodystrophies, in which myelin breaks down beginning in childhood. Goldman’s laboratory has had unprecedented success using stem cells to extend the lifespan of mice with pediatric leukodystrophies, and the team hopes to begin clinical trials in children within the next few years, in part based on the findings to be obtained in these related projects.