Personnel Director Curt R. Freed, M.D. Professor of Medicine and Pharmacology Professor of Medicine and Pharmacology Head, Div CP and Tox Head, Div CP and Tox Director, Neuroscience Program Director, Neuroscience Program Neurosurgeon andRobert E. Breeze, M.D. Co-DirectorProfessor of Neurosurgery Neurologist Maureen A. Leehey, M.D. and Co-Director Assistant Professor of Neurology Director, Movement Disorders Director, Movement Disorders Clinic, University Hospital Clinic, University Hospital

New Strategies for Neurotransplantation --Repairing the Fetal Brain in Utero --Repairing the Fetal Brain in Utero 1. In collaboration with scientists at Harvard, we have implanted neural stem cells into the developing brain of monkeys. 2. Transplanted cells have survived and have grown into appropriate layers of the developing monkey brain, showing the potential to repair cell deficits.

How stem cells may repair brain of Down’s syndrome patients 1. All cell in Down’s syndrome patients carry trisomy- 21, so stem cells always produce abnormal progeny. 2. Normal stem cells transplanted to the fetal brain in utero could supply normal brain cells during brain development. 3. Because dementia takes decades to develop, transplants of normal stem cells at any age may reduce and perhaps reverse brain deterioration.

What is the difference between “adult” and “embryonic stem cells? 1. Nearly all organs in the body have stem cells to replace cells that wear out. Skin, bone marrow, intestine and brain. Ordinarily, stem cells from each organ make cells only for that organ. 2. Embryonic stem cells are the few hundred cells that make up embryo in the first days after fertilization. They can become any cell in the body.

What diseases are now treated with stem cells? 1. Bone marrow transplant after massive doses of chemotherapy or because of specific kinds of anemias. 2. Skin grafts and bone grafts include stem cells from those organs.

What diseases may be treated with stem cells in the future? 1. If embryonic or adult stem cells can be made into insulin producing cells or dopamine neurons, treatment of diabetes and Parkinson’s can be revolutionized. 2. Embryonic or adult stem cells will be used to treat patients whose own stem cells have failed or are genetically flawed. These might include Down’s syndrome, Alzheimer’s, heart failure, diabetes, and anemias.

What is the chance that stem cells approved for NIH funding will be used for human therapy? Almost zero. All human embryonic stem cells have required co- culture with mouse cells. Only when mouse cells are not needed can new cell lines be developed for human therapeutic use.

Summary of “adult” brain cells 1. Stem cell therapy with bone marrow has been available for decades. 2. “Adult” stem cells derived from specific tissue like embryonic brain or adult bone marrow are under development for therapeutic transplant. 3. Degenerative brain diseases, both fetal and adult, will likely be successfully treated with these stem cells.

Summary of “embryonic” stem cells 1. Embryonic stem cells offer great promise for becoming the universal cell source, if the cells can be guided to specific tissue types. 2. Therapeutic cloning may be necessary to produce cells that won’t be rejected.

Link between embryonic stem cells and “therapeutic cloning” 1. Stem cells developed from another individual will be rejected by the recipient unless transplanted in utero or into the brain. 2. “Therapeutic cloning” refers to the production of embryonic stem cells from one cell of a patient needing a transplant. Heart muscle cells or insulin-producing cells would be identical to the patient.