Reprogrammed Human Cells Shed Light on Rare Disease

A new study uses induced pluripotent stem cells to investigate a neurological disease and test drugs.

Stem cells generated from patients with a rare neurological disorder are helping scientists dissect the underlying mechanism of the disease and test several candidate drugs. The study, published today in Nature, is the realization of one of the major goals in stem cell research: using induced pluripotent stem (iPS) cells--stem cells derived from reprogrammed adult cells--to study the effects of disease in a patient's own cells, which are otherwise impossible to access.

Mirroring disease. By taking skin cells from patients with a rare neurological disease, researchers were able to create stem cells that could be turned into the specific neurons (shown here labeled with red and blue markers) affected by the disease. Credit: Gabsang Lee and Lorenz Studer.

The work is "a blueprint for the future of using stem cells to study and treat neurological disease," says Jeanne Loring, director of the Center for Regenerative Medicine at the Scripps Research Institute. (Loring was not involved in the study.)

The idea is simple: Take skin cells from patients with a particular disease, turn those cells into stem cells, direct those stem cells to become a cell type of interest--for instance, the dopamine-releasing neurons that are affected by Parkinson's disease--and see how those cells behave and react to different drugs. A spate of recent papers has demonstrated the development of disease-specific stem cells for conditions such as Down syndrome, amyotrophic lateral sclerosis, spinal muscular atrophy, and Parkinson's disease. The new study is the first to use cells derived from iPS cells to test drugs for their effect against a disease.

Lorenz Studer, lead author of the paper and a developmental biologist at the Sloan-Kettering Institute in New York, and his team focused on a rare disease called familial dysautonomia (FD), which affects neurons that control functions such as the sensation of touch, blood pressure and tear flow. Symptoms usually arise early in life, sometimes from birth, and include a lack of muscle tone and reflex control, problems sensing pain, high blood pressure and difficulty breathing. The disease is caused by a known genetic mutation, but scientists have been unable to create an animal model of the disease.

Story continues below

The researchers obtained skin cells from patients with FD and created lines of iPS cells by inserting four genes into the cells using viruses. This reprogrammed the cells to behave like embryonic stem cells, which can give rise to all cell types. The researchers then directed those undifferentiated cells to turn into specific cell types, including the neural crest cells that give rise to the neurons affected by FD.