This open access review covers attempts by the research community to produce a cell therapy to treat Parkinson's disease, a condition driven by the accelerated loss of a small but vital population of brain cells. This loss happens to everyone over the course of aging to a much lesser degree, and thus progress towards treatments is of general interest. In theory these lost cells could be replaced, but in practice getting to the point of a reliable treatment along those lines is entwined with the ongoing development of stem cell medicine as a whole. Robust methods of cell production, transplant, and engineering, along with sufficiently comprehensive knowledge of cell biology to steer this work are all still in progress, further along for some types of cell and tissue, less well advanced for others:
Parkinson's disease (PD) is one of the most common neurodegenerative disorders of aging, affecting about 1% of the population aged 60 years and older and 3-5% of the population above the age of 85. The various disruptions in motor control typically appear when 60-80% of dopamine (DA) neurons in the substantia nigra are degenerated. Because DA neurons degenerate to cause a drop in dopamine release, current treatments for PD include dopamine replacement drugs and deep brain stimulation (DBS) to the nucleus subthalamicus. Even though dopamine replacement drugs and DBS are effective in improving the symptoms of the patients, they cannot stop the disease progression. Moreover, current medications can cause the development of involuntary muscle movements, effectively "overshooting" the clinical symptoms of PD.
Recent research progress has provided treatment potential through replacing lost DA neurons using neural stem cells (NSCs) or fully differentiated DA neurons from fetal brain tissue, embryonic stem cells (ESCs), mesenchymal stem cells (MSCs) sourced from adults or fetuses, and induced pluripotent stem cells (iPSCs) reprogrammed from patients' somatic fibroblasts or blood cells. Much work has been done to adapt cells from various sources to potential clinical applications to improve treatments for neurodegenerative diseases including PD. NSCs and DA neurons from fetal brain and hESCs are not suitable for clinical use because of their immune-rejections and ethical issues. The availability of iPSCs and iDA neurons paved the road for autologous cell-based therapy of PD. However, several aspects of iPSCs need to be resolved before they go to clinical use. These include low yields of DA neurons, genetic and epigenetic abnormalities, and the safety of iPSC-derived cells.
Cell replacement therapy is a promising avenue for the treatment of PD and other neurodegenerative disorders. The use of all cell sources derived is fraught with ethical, logistical, and safety concerns. However, scientific research is making great progress in the development and characterization of iPSC derived cells for PD. iPSCs and their derivatives injected into animal models have shown promise in treatment of disorders such as PD; however, iPSCs have not been used in clinical trials for PD. There are some limitations/disadvantages associated with iPSCs. A relevant therapeutic progenitor or mature cell type may be identified and grafted in such treatments; in the case of PD, the options are, of course, iPSC-derived NSCs and iPSC-derived DA neurons. Theoretically, these two should act just like their non-iPSC derived counterparts - in actuality, because of the concerns mentioned above, the unique iPSC heritage of such cells sometimes poses its own unique set of problems.
Pre-clinical studies on viability might also be necessary to establish the scope of the treatment. iPSCs would not be moved to clinical trials at least until iPSCs are better understood and efficient and safe methods for reprogramming and gene correction are developed. The pace of progress will no doubt continue to speed along in the years to come, and it is therefore quite likely that within our lifetime we will witness the jump from dish to clinic.