Stem Cell Program | Neurologic Disorders

Neurologic disorders can be devastating, because the nervous system controls how we move, how we communicate, how we think — in short, how we interact with the world around us.

Conditions, such as spinal cord injury, can mean difficulties not just for a child, but for a child’s loved ones as well. At Boston Children’s Hospital, our doctors are committed to helping your family through these adjustments, while our stem cell researchers are committed to understanding how these conditions develop and finding new ways to treat them. This work may help future doctors replace nerve cells damaged from injury or genetic disease with healthy and functioning cells.

Our work with stem cells includes development of methods to create clinical-grade induced-pluripotent stem cell lines. These stem cells can then be turned into therapeutic cell products to replace cells damaged by neurologic disorders. 

We also work on the creation of patient-specific induced pluripotent cells to model and study the development of diseases such as Huntington disease, Parkinson disease, and inherited retinal degeneration, as well as the repair of disease-causing genes using state-of-the-art genome editing methods including CRISPR-Cas9 and Base Editing.

Huntington disease and Parkinson Disease

George Daley, MD, PhD, led his team in creating the first set of induced pluripotent stem cells (iPS cells) from patients with neurologic disorders including Huntington disease (HD) and Parkinson Disease (PD). The team created each of these stem cell lines by turning skin cells from afflicted patients into immortal and pluripotent iPSCs, giving scientist the opportunity to perform disease modeling in a dish to see how the respective diseases develop and to study how they could be treated. For example, the mutation that causes HD can be removed by genome editing, and the dopaminergic neurons lost in patients suffering from PD can be replaced by hiPSC-derived cells. Indeed, PD patients are among the first who underwent cell replacement therapy with dopaminergic progenitor cells made from their own hiPSCs.

Retinal degeneration

Blindness often results from progressive deterioration of the retina, as is the case in age-related macular degeneration (AMD) or hereditary retinopathies. Working together with centers in Iowa and Taipei, the Stem Cell Program’s Stem Cell Core (led by Thorsten M. Schlaeger, PhD), generated hiPSC lines to model Leber Congenital Amaurosis (LCA) and X-Linked Retinoschisis (XLRS). Schlaeger’s team used CRISPR/Cas9 mediated genome editing to precisely repair the disease-causing mutations in several LCA and XLRS patient-derived hiPSCs. Using an efficient and precise genome editing technique called Cas9 Base Editing, they were able to repair the mutant gene in over 50 percent of XLRS patient derived hiPSCs. Retinal cups made from the repaired cells no longer showed the structural and developmental defects seen in mutant retinas, suggesting that a Cas9 based gene therapy approach could cure this disease. Age-related macular degeneration, a leading cause of vision loss, is another disease for which hiPSC-based clinical trials have already begun in Japan as well as in the US. In these trials, sheets of retinal pigment epithelial cells, a cell type is critical to nurture and maintain a healthy retinal, are made in a dish from hiPSCs and then inserted into the patient’s retina underneath the affected photoreceptor cells.

Spinal cord injury

Because of stem cells’ potential for regenerative medicine, scientists are interested in being able to make nerve cells out of pluripotent stem cells or neural stem cells. In mouse models of disease, transplanted nerve cells derived from stem cells survive and live on to improve neurological functions. In 2009, the FDA approved a Phase I clinical trial for cell-based product (oligodendrocyte precursor cells) to stimulate the re-growth of nerve tissue in spinal cord injuries, a concept validated by previous experiments in mice. This is the first FDA-approved trial for any human embryonic stem cell-based therapy. A hiPSC-based trial for spinal cord injury is also being planned.