On March 9, 2009, President Barack Obama signed an Executive Order that calls for fair and ethical funding and oversight for embryonic stem cell research. In doing so President Obama has reversed previous federal legislation restricting embryonic stem cell research to a limited number of cell lines created before August 2001. The new policy ensures that Americans are no longer forced to look back at what could have been, but can instead look forward to one day seeing the promise of scientific and medical research fulfilled.

But what are the practical implications for Parkinson’s disease research — and what does the news mean for people living with PD? Brian Fiske, PhD, associate director, team leader, research programs, at The Michael J. Fox Foundation, answered basic questions on the new policy and the state of cell replacement therapy as a treatment approach for Parkinson’s disease.

What does the executive order actually say and what has changed?

The new policy states that federal funding can be used to support work with human embryonic stem cells. This reverses legislation signed by President George W. Bush on August 9, 2001, significantly limiting U.S. federal research funding for embryonic stem cell research. Under the Bush administration, federal funding for embryonic stem cell research could be obtained only for projects conducted on one of the 64 stem cell lines created prior to August 9, 2001.

Even before President Obama’s executive order, weren’t Parkinson’s scientists able to continue stem cell research using other kinds of stem cells like adult and induced pluripotent stem (iPS) cells?

Embryonic stem cells remain the ‘gold standard,’ although a variety of different sources and methods for generating stem cells now exists. These include adult stem cells and iPS cells. IPS cells are created by expressing a combination of four genes related to stem cells in an adult human skin cell. This causes the adult cell to revert to a state where it can become any kind of cell in the body. It’s a way to “reprogram” the cell to become more like an embryonic stem cell.

Based on research results to date, Parkinson’s scientists have had greater success deriving dopamine neurons from authentic embryonic stem cells than from other stem cell sources. While research using adult stem cells has yielded dopamine neurons, the resulting neurons have not been as robust in quantity or in quality as those generated using embryonic stem cells.

The recent development of methods to generate human iPS cells represents a breakthrough. Research continues to accelerate around these cells, including a report earlier this month demonstrating ability to generate iPS cells from people with Parkinson’s disease. There also have been early reports that iPS cells can improve deficits in pre-clinical models of PD.

Although cell replacement approaches remain far off from practical deployment in the clinic, in the shorter term there is hope that dopaminergic neurons generated from human iPS cells can provide a glimpse into the underlying causes of the disease. Researchers can also use these cells in the laboratory to screen for drugs that could impact the disease process.

But to succeed in making these new cells useful, whether for drug discovery or for cell replacement therapies, still requires that we understand the real thing — embryonic stem cells. It’s important to remember, too, that iPS cells are affected by all the scientific challenges that embryonic stem cells suffer with respect to getting them to function and survive safely in a host brain. So they are by no means a sure thing at this stage.

However, with the new policy put in place by President Obama, the scientific community has far greater latitude to address these challenges.

In that case, given the new policy, will we soon see new cell replacement approaches to Parkinson’s entering clinical trials?

While the new policy will have a major impact on pushing cell replacement therapy forward, several issues remain as hurdles to therapeutic relevance of this work for Parkinson’s disease. For example, though scientists are getting closer to creating ‘authentic’ dopamine neurons — that is, neurons that can do and express everything natural ones can — important details of what makes up a true dopamine neuron remain unknown. And even when researchers have obtained seemingly authentic dopamine cells, only limited success has been achieved in coaxing these cells to incorporate into host animal brains without dying, turning into a different cell type or, in some cases, causing uncontrollable cell growth. There are other issues as well. We still don’t know exactly the best spot for placing the cell grafts. Another major issue is optimizing delivery of cells to a host brain without causing additional brain damage.

Remember that in the early attempts at grafting fetal tissue into human patients, severe clinical complications arose in some cases, including off-medication dyskinesias. There is no guarantee that stem cell-derived tissue transplants won’t suffer similar problems, and overcoming these challenges is essential before work can go forward toward the clinic.

I heard that the FDA recently approved the first clinical trial involving a human embryonic stem cell therapy for spinal cord injury. Was this made possible by the Executive Order?

No. In fact, the announcement of that trial preceded the President’s Executive Order. Both Geron (the company sponsoring the trial) and the FDA told The Wall Street Journal that the timing of the decision to approve the study was coincidental. The WSJ quoted an FDA spokeswoman as follows: “The FDA looks to the science on these types of issues, and we approve [such applications] based on a showing of safety. Political considerations have no role in this process.”

However, the Geron trial does alter the landscape to some extent, in that scientists now have a regulatory path and precedent they can follow. The challenges for a Parkinson’s stem cell trial will of course differ from what Geron is doing (e.g., different type of cells will need to be generated, different transplant methods used, and so on). But the trial is likely to energize companies and researchers to start seriously pushing forward again toward potential stem-cell-based intervention trials for other diseases, including PD.

What is The Michael J. Fox Foundation’s view on cell replacement therapy and the new policy?

We applaud President Obama’s commitment to embryonic stem cell research and to ensuring that its promise continues to be explored for the benefit of every individual whose life is touched by illness or injury. Based on evidence available to date, the Foundation believes that the development of viable and feasible cell replacement therapies could revolutionize the treatment of Parkinson’s disease. Nonetheless, the scientific hurdles necessary to achieve therapeutic success with cell replacement are great, and much work remains to be done before cell replacement therapy for PD is a viable therapy for patients.

What does Michael J. Fox say?

Though out of the country, Michael J. Fox issued the following prepared statement on the President’s decision:

“Today is a new day. I could not be more thrilled to see President Obama live up to his commitment to get politics out of science. We have seen, for the past eight years, how much damage the opposite approach has done to science and patients. Now that the President has taken this critical action, I am excited by the prospect of American scientists carrying human embryonic stem cell research forward toward better treatments and cures that will affect countless millions of lives.

“I commend the President for recognizing the inherent value of scientific freedom, and for helping to create an environment in which it can flourish.”