Cell Replacement Therapy for Parkinson's Disease

How Close Are We to the Clinic?

Javier Ganz; Nirit Lev; Eldad Melamed; Daniel Offen


Expert Rev Neurother. 2011;11(9):1325-1339. 

In This Article

Conclusion & Perspectives

Regenerative medicine has an extraordinary potential to ameliorate the quality of life of PD patients and offers a possible cure for PD. The initial clinical trials in CRT for PD employed embryonic mesencephalic grafts, and provided proof of principle that DA cell replacement can be achieved and, in selected patients, can accomplish significant, long-lasting improvement of motor function. On the other hand, the excitement generated by the early open-label trials were diminished by the subsequent placebo-controlled, double-blind trials. Nevertheless, accumulated data and several fascinating breakthroughs in stem cell research created an opportunity for better and safer CRT options (e.g., transplantation of autologous bone-marrow-derived stem cells). In the previously decades, our basic knowledge about stem cells and the potential CRT for PD has grown exponentially, as seen by increasing scientific publications. A vast progress was obtained in generating human-derived DA neurons from different stem cell sources. Specifically, we achieved one of the first milestones for CRT, which consists of producing large quantities of standardized human stem cell-derived midbrain DA neurons in vitro. However, their efficient and safe application in animal models of PD has not yet been achieved. As stated by Arenas et al., in order to advance on the CRT pathway, we need to: improve protocols for the generation of midbrain A9 DA neurons; identify markers and develop protocols for the separation of transplantable cells; eliminate any chance of tumor formation or neural outgrowth; prevent excessive inflammatory response; improve imaging methods to monitor graft and DA cell function in vivo; improve animal models of PD to recapitulate more features of the disease and increase predictability; eliminate the response from the host to xenografts or increase tolerance; and comply with Good Manufacturing Practices and the increasing regulatory requirements.[2] There is a long way to go in order to successfully translate the generated knowledge into safer clinical applications. Currently, two PD–CRT clinical trials are in progress. These long-expected trials are currently in Phase I and III and include autologous bone marrow MSC transplantation[202] and embryonic DA mesencephalic cell transplantation,[203] respectively. Multidisciplinary research must be carried out, combining basic and clinical research, in order to step forward on the road of CRT in PD.