The Brain Program at the Cedars-Sinai Regenerative Medicine Institute comprises a group of scientists studying a variety of neurological diseases of the peripheral and central nervous system using stem cell technology as their primary research tool. Several groups have a particular focus on using induced pluripotent stem cells (iPSCs) to research neurological diseases.
Skin cells from patients can be converted into iPSCs, which are matured into the affected neurons or other nervous system cell types such as astrocytes, Schwann cells or oligodendrocytes. Scientists in the Brain Program can then study these cells in a dish to assess disease initiation, progression and possible treatment. This “disease modeling in a dish” was unattainable prior to the development of iPSC technology.
In addition, several researchers in the Brain Program are interested in transplanting human neural stem cells derived from iPSCs and other sources into animal models of degenerative diseases and stroke to determine if these cells can be used for treatment.
Other groups in the Brain Program focus on the molecular signals that regulate neural stem cell behavior and how these signals may go awry and lead to brain tumors. Using patient-specific mutations to create tumor models in animals, they are uncovering more targeted treatments to halt the progression of these malignancies. The Brain Program covers a diverse set of neurological conditions, from degenerative diseases such as Alzheimer’s, Huntington’s, Parkinson’s, and amyotrophic lateral sclerosis (ALS) to stroke and cancer. Peripheral nervous system diseases, like Charcot-Marie-Tooth disease, are also studied.
Patient skin cells were obtained, converted into iPSCs and subsequently matured into neurons in a culture dish, which are labeled in green. Using this technology, we can directly study neurons from patients with brain and spinal cord diseases to develop new therapies.
The Brain Program is the recipient of the largest research grant ever awarded to Cedars-Sinai. The grant, funded by the California Institute for Regenerative Medicine (CIRM), is for the development of stem cell treatments for patients with ALS, also known as Lou Gehrig’s disease — a progressive, fatal and currently incurable neurodegenerative disease.
Stem cells have the potential to protect damaged motor neurons in ALS, as does a protein called glial cell line-derived neurotrophic factor (GDNF). However, direct GDNF delivery to the brain or spinal cord has been impossible because GDNF does not cross the blood-brain barrier. For a novel treatment, the Brain Program is generating stem cells that make GDNF, and is then transplanting these stem cells into the affected spinal cord to protect sick neurons.
The Brain Program recently received National Institutes of Health (NIH)/CIRM funding for the development of potential therapies to treat Huntington’s disease, an incurable neurodegenerative genetic disorder that severely affects movement and cognitive functions. We are collaborating with the Cedars-Sinai iPSC core, which has produced 15 new iPSC lines from patients with mild to advanced Huntington’s disease.
The Brain Program is also investigating
- new ways to control gene expression in cells for use in gene and stem cell therapy.
- strategies for genetic engineering of stem cells derived from patients with an inherited disease, to “fix” the genetic defect. These cells will be used to test new therapeutics and to potentially replace damaged nervous system cells in future clinical trials.
The Brain Program brings together a team of scientists, neurologists, and neurosurgeons, as well as develops collaborations with other specialty areas. The research also involves collaborations with other institutions, including Emory University in Georgia and California Pacific Medical Center.