Nurr-1 induction of a dopaminergic neuronal fate in a neural stem cell or neural progenitor cell in vitro

Patent Number: 7,465,582

Various organs have regenerative capabilities, which are believed to occur as a result of endogenous stem cells or progenitor cells.  This has been described in the liver, pancreas, heart, and even brain.  Although there is controversy as to whether the tissue specific progenitors are residual fetal cells, or continually renewed by a circulating bone marrow derived source, it is established not only that endogenous repair cells exist, but also that they can be augmented by exercise or administration of various drugs. 

One interesting therapeutic possibility is if neural stem cells can be expanded ex vivo and subsequently administered to patients in need.  Neural stem cell isolation using CD133 purification is the subject of patent #6,468,794 held by StemCells Inc who is currently in clincal trials with this approach.  Other means of isolating neural stem cells include purification based on expression of CD49f (#7,381,561), and CD15 (#7,419,825). 

The current patent teaches methods of inducing differentiation of neural progenitor cells into dopaminergic neurons.  The method comprises of two steps.  The first step consists of incubating in vitro a neural stem cell or a neural progenitor cell that overexpresses Nurr-1.  The second step is to incubate the selected cell with a Type 1 astrocyte of the ventral mesencepahlon.  This co-culture system has been demonstrate by the inventors to consistently generate dopamine producing cells. 

The patent can be used not only for adult stem cells but also for iPS or ES generated progenitors since the restriction on the progenitor is " neural stem cell or a neural progenitor cell that overexpresses Nurr-1, wherein Nurr-1 in the cell is overexpressed when compared to an unmodified neural stem cell or neural progenitor cell in vitro under non-pathological conditions"

Nurr-1 is a nuclear receptor that is found in cells giving rise to dopaminergic cells.  Why this is important is because in Parkinson's the dopaminergic neurons of the substantia nigra deteriorate, thus causing pathology.

View this patent on the USPTO website.