Tag Archive | "parkinson’s disease"

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New Study Yields Unique Drug Responses With Patient-Derived Stem Cells

A new study of mitochondrial deficits in iPSC-derived neural cells, funded by the National Institutes of Health and published in Science Translational Medicine, shows that patient-derived stem cells yield differing responses for cells derived from patients with different etiologies of Parkinson’s disease. The study suggests that Parkinson’s intervention may someday be tailored to individuals based upon the genetic cause of their illness.

Parkinson’s disease is a debilitating illness that affects multiple regions of the brain. In the region of the brain that controls motor activity, the disease destroys critical dopamine-producing neurons. The loss of these neurons, with the associated loss of dopamine, leads to muscle stiffness, slowed movements, and eventually to the involuntary shaking that is the classic symptom of Parkinson’s. There is currently no known cure for the disease.

Genetics is known to play a strong role in the development of Parkinson’s. Seventeen regions of the human genome have been identified where common variations in sequencing appear to increase the risk of developing the disease. Researchers have also identified nine specific genes that can mutate to cause Parkinson’s.

In the study, neurons were derived from the skin cells of patients with various inherited forms of Parkinson’s disease. Mitochondrial deficits associated with Parkinson’s were observed across all the samples, and the cellular responses to treatments varied according to the specific type of Parkinson’s afflicting the donor patient.

The skin cells were first transformed into induced pluripotent stem cells. These cells, called iPS cells, are adult cells that have been reprogrammed to mimic embryonic stem cells. The cells were then manipulated into become neurons through a combination of growth-stimulating molecules and favorable conditions.

The study used iPS cells derived from patients with mutations in the leucine-rich repeat kinase 2 enzyme that is encoded by the PARK8 gene and from patients with mutations in the PTEN-induced putative kinase 1 serine/threonine-protein kinase that is encoded by the PINK1 gene. Both of these mutations are known to cause Parkinson’s disease.

The researchers monitored the oxygen consumption rates of the mitochondria in the derived cells. Mitochondria use oxygen to produce cellular energy from glucose, and Parkinson’s disease has been linked to a breakdown of mitochondrial function.

Oxygen consumption rates were observed to be lower in the cells derived from patients with LRRK2 mutations and higher in cells derived from patients with PINK1 mutations. Administration of the immunosuppressant rapamycin was found to help prevent damage to LRRK2 mutated cells but not neurons with PINK1 mutations.

These results suggest that Parkinson’s originating from different genetic causes may benefit from different medical treatments, and iPS cell technology could be used to identify subgroups of clinical trial patients. Parkinson’s intervention trials have never before focused on specific genetic groups.

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