Given the overall similarity and the ability to bypass the immune response, interest in using iPSCs for therapy has been high. Recently, iPSC lines from sporadic PD patients have been generated [8] and several groups have now shown that gene targeting can be performed with roughly the same efficiency as in hESCs, and that iPSCs from people carrying known mutations can be harvested and propagated [22,23]. Although PD is usually sporadic, genetic studies have, however, identified mutations in several genes, including LRRK2, parkin, α-synuclein, uchL1, PINK1, DJ-1, and ATP13A2, in familial PD. We, therefore, initiated an effort to generate iPSC lines from familial PD patients with defined mutations. As a proof-of-principle experiment, we derived an iPSC line from skin biopsies obtained from a PD patient with a defined mutation in LRRK2 as mutations in LRRK2 account for approximately 7% of familial PD cases and a significant portion of sporadic PD cases [24,25]. Using the identical differentiation protocol, we derived Sox1+/Nestin+ NSCs from the LRRK2 iPSC line. Further analysis of potential phenotype during dopaminergic differentiation associated with the mutation in familial PD patient lines is the scope of our future work.
