The endeavor to find better treatments or perhaps even one day a cure for a host of debilitating and fatal neurological diseases has been bolstered by an influx of funding from a mix of private and public sources.

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 feared disorders for which there are currently no cures – including multiple sclerosis, Huntington’s disease, and fatal childhood diseases known as pediatric leukodystrophies.

Goldman’s research is at the forefront of attempts to harness the promise of stem cells to benefit patients who suffer from neurological diseases. To help patients by using stem cells and their close cousins, including progenitor cells and pluripotent cells, scientists like Goldman are learning about the molecular cues involved in directing the actions of those cells. Some signals, for instance, help prod stem cells to become brain cells called neurons, while others direct them to become glial cells. Understanding the elaborate labyrinth of signals involved is crucial for physicians who would like be able to put stem cells into patients and have the cells develop into just the types necessary to help those patients.

Two newly funded projects focus on the molecular events involved in the repair of myelin, a critical substance in the brain that breaks down in conditions such as multiple sclerosis, as well as in a number of hereditary childhood diseases. 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. In MS patients, the myelin coating of nerve fibers breaks down, so that nerve cells stop signaling efficiently. Patients with MS then suffer symptoms such as weakness and a loss in sensation and coordination. 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 MS 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 second 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 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 and related 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. Many of those diseases kill young children only after they have endured a near lifetime of symptoms like seizures, falls, blindness, and diminishing cognitive abilities. 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.