Skin cells may aid Parkinson's therapy

Boston - Researchers may have come closer to finding more effective treatment for Parkinson's disease by investigating signs of the disease in patient-derived skin cells and testing how the cells respond to drug therapy.

In a small study, researchers led by neurology professor Ole Isacson, M.D., Ph.D., McLean Hospital and Harvard Medical School, collected induced pluripotent stem (iPS) cells - adult cells that are reprogrammed to behave like embryonic stem cells - from five patients with genetic forms of Parkinson’s disease. They found that neurons derived from individuals with distinct types of Parkinson's showed common signs of distress and vulnerability, particularly abnormalities in mitochondria.

Three patients had mutations in a gene called LRRK2, and two others were siblings who had mutations in the gene PINK1. The researchers also derived iPS cells from two of the siblings’ family members who did not have Parkinson’s. Since it is believed that Parkinson’s involves a breakdown of mitochondrial function, investigators looked for signs of impaired mitochondria in patient-derived neurons. Mitochondria turn oxygen and glucose into cellular energy.

Oxygen consumption rates were found to be lower in patient cells with LRRK2 mutations and higher in cells with the PINK1 mutation. In PINK1 mutant cells, the researchers also found increased vulnerability to oxidative stress, a damaging process that in theory can be counteracted with antioxidants.

Researchers also examined whether neurons derived from patients and healthy volunteers were vulnerable to a variety of toxins, including some that target mitochondria. They attempted to rescue the toxin-exposed cells with various drug treatments that have shown promise in animal models of Parkinson’s, including the antioxidant coenzyme Q10 and the immunosuppressant rapamycin.

All patient-derived neurons had beneficial responses to CoQ10. However, the patient-derived neurons differed in their response to rapamycin, which helped prevent damage to neurons with LRRK2 mutations but did not protect the neurons with PINK1 mutations.

The study was published in Science Translational Medicine.

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