Brain and Nervous System

Parkinson's Disease

Parkinson’s disease is one of the most common neurodegenerative disorders, affecting 1 in 100 people over age 60. We are developing a cell-based strategy to restore lost function, which results from progressive neurodegeneration associated with Parkinson’s disease.

The symptoms of this disease, including tremor, rigidity, and slowness of movement, result from an alteration in the level of activity of brain circuits underlying motor control. We seek to treat the disease by restoring normal levels of activity in these brain circuits. We use a specific class of stem cells that produce inhibitory nerve cells in the embryonic brain, the MGE cells, as donor cells to inhibit those brain regions that are abnormally active in Parkinson’s disease.

This program integrates the research programs headed by Drs. Arturo Alvarez-Buylla, Krys Bankiewicz and Arnold Kriegstein. We developed the technology to prepare large numbers of embryonic donor cells, which after transplantation survive, migrate and integrate into the pre-existing neuronal circuits.

In animal models of Parkinson’s disease, the transplanted cells improved performance in motor tasks designed to mimic deficits encountered in human patients. We are expanding these studies, perfecting the transplant procedures, and exploring human donor cells as steps toward therapeutic trials in patients.

The translation of laboratory discoveries into delivered therapeutics will be aided by UCSF’s comprehensive clinical research programs focused on Parkinson’s disease. UCSF has been a National Parkinson's Foundation Center of Excellence since 1992, and encompasses neurologists, neurosurgeons, neurophysiologists, and nurse specialists with the capacity to design, execute and interpret clinical trials involving biological and surgical treatments.

Epilepsy

Epilepsy is marked by recurring seizures due to abnormal activity of neurons in the brain. This disease affects 2 million people in the US, and as many as 150,000 more develop epilepsy each year, about a third of them children.

As part of an integrated approach to use neural MGE stem cells for cell-based therapy, the laboratories of laboratories of John Rubenstein, Scott Baraban and Arturo Alvarez-Buylla are collaborating to test whether grafted cells can be used to correct or ameliorate the hyper-excitability that causes epilepsy. Preliminary studies using animal models of acquired and genetic epilepsy indicate that grafted MGE cells functionally integrate in the host brain and increase the overall level of inhibition and reduce seizure frequency.

These results are the first indication that grafted cells can increase cortical inhibition and ameliorate seizure activity in epilepsy. An early use of this approach may be to treat intractable childhood epilepsy, where the only current treatment is surgical ablation of large brain regions.

• Participating Faculty and Labs