Disease Focus Series: Parkinson’s Disease and promising new pre-clinical results from iPS cells

UPDATE: A second recent study, this one in Nature Genetics has found a novel genetic link between the immune system and Parkinson’s. The authors were screening for genomic variants unique to Parkinson’s patients, finding known ones but also a novel linkage. The link was with the HLA region, known to play a key role in immunity. This study supports the hypothesis that is gathering steam in the field that there is an immune component to PD, specifically an inflammatory aspect to the disease. This finding may give further weight to the notion of immune-related drug development. In addition it supports the notion of potentially use MSCs to modulate immune function in the brain to treat PD.

Parkinson’s Disease (PD) is a neurodegenerative disorder that strikes more than a million Americans. Symptoms of PD include movement disorders such as tremor as well as muscle rigidity arising from problems with the function of dopaminergic neurons.

The disease is progressive, taking an ever more severe toll on patients as they age.

In the vast majority of cases, the causes of PD are unknown, which unfortunately presents a research challenge for prevention and treatment.  However, a great deal of research is ongoing and I’m particularly excited about regenerative medicine approaches to treating PD patients.  Research funded by the Michael J. Fox Foundation and by CIRM are both making progress. Just this week, CIRM-funded research was reported that is an exciting step toward stem cell-based treatments for PD.

Reporting their findings in the journal, Stem Cells, Xianmin Zeng and colleagues at the Buck Institute (press release here) tested treating PD in an animal model using human iPS cells. You can see the actual paper here (warning:link to  PDF). They first used the iPS cells to make dopamine-producing neurons.

These neurons and/or neural progenitors destined to make these neurons were transplanted into rats with a chemically-induced Parkinson’s Disease-like disorder. Encouragingly, the transplants improved the PD-like symptoms of the rats during the course of the study. While the PD treatment related results are somewhat preliminary and limited in scope, the findings are nonetheless very exciting and this represents an important step forward to treating PD.

This study provides evidence that iPS-cell based therapies could one day lead to a cure or effective treatment for PD, and it would require no immunosuppression. Work with hESC is also promising and may actually work as well or better than that with IPS cells, although the jury is still out on that and such a hypothetical therapy would require immunosuppression. One detail missing from the paper as far as I could tell is how many cells were actually used for each transplant. It appears about 2,000 cells engrafted, but out of how many?

At least for the apparent 12 week course of this study, another important aspect is that no teratoma or other tumors were reported, giving reason for hope that iPS cell based treatments more generally can indeed be made safe. As readers of this blog know, that is an area that I am very concerned about. One potential issue is whether 12 weeks post-transplantation is long enough to test for teratoma or pre-teratoma like lesions as even in immunodeficient mouse models, it sometimes takes up to 3 months for teratoma from hESC to develop.

Overall, this is a very interesting and encouraging paper.