The ultimate goal of stem cell research for Parkinson's disease (PD) has historically centered on generating healthy dopamine neurons to replace those dopamine neurons that die in the disease, in turn slowing or even reversing the progression of PD. Though this is likely still years off, stem cells are currently being used by researchers in another way that could turn out to be just as critical Ė as research tools for developing new Parkinsonís drugs.
The novel science at work surrounds induced pluripotent stem cells (iPS), adult human-derived cells that, like embryonic stem cells, can become any of the major cell types in the body. iPS cells are currently being used to create models that allow researchers to study and validate mechanisms underlying PD. Already, insights gained from this research have begun to provide better models to screen drug candidates that could, in the future, become new treatments for people with Parkinsonís.
Hereís the major plus to iPS cells: Scientists can generate iPS cells from PD patients and compare them to cells from people who donít have the disease, making it possible to identify biological mechanisms uniquely associated with Parkinsonís. To date, scientists engaged in early Parkinsonís research have had to create artificial models in the lab that mimic the disease, by using cancer cells or animal-derived cells. These models donít fully represent disease process or specific symptoms taking place in PD, inefficiencies that can provide a major roadblock to developing drugs that work in people. iPS-derived neurons could help to overcome this roadblock.
Another plus to iPS cells: Scientists can create them from someone who is still living. This means they can create studies combining clinical observational data (a personís phenotype) with scientific renderings of their genetic makeup (their genotype) for a more holistic understanding of what may be happening in an individualís experience with a disease Ė vital information for making effective drugs.
ďiPS cells provide clues to a critical piece of a sort of disease jigsaw puzzle,Ē says Kalpana Merchant, PhD, Chief Scientific Officer at Eli Lilly. ďThe more pieces we can pull together, the better chance we have of developing treatments to treat diseases like Parkinsonís.Ē
Several Fox awardees have made important progress working with iPS cells. In February 2012, a team at the University of Buffalo announced that they had successfully produced live human neurons to investigate the role that the parkin gene plays in PD, the first ever team to do so.
"Before this, we didn't even think about being able to study the disease in human neurons," admitted study lead Jian Feng, PhD. But, now thanks in part to Dr. Fengís team, researchers can.
Dr. Fengís study is one of four being supported by MJFF to better understand how iPS cells could be used to develop new treatments for PD.
Ole Isacson, MD, of Harvard Medical School, in conjunction with National Institute of Neurological Disorders and Stroke (NINDS), is leading an iPS Cell Consortium to generate many iPS cell lines from PD patients. Others in this consortium are leading similar efforts for Huntingtonís disease (HD) and Amyotrophic lateral sclerosis (ALS). These iPS cells are made available to researchers worldwide to better understand underlying disease mechanisms. One example: the PD consortium has already begun to identify key molecular pathways that could be used to test drug candidates.
According to Merchant, initial successes have fueled tremendous growth in iPS cell-driven research. The real promise will depend on the availability of hundreds of iPS cell lines that must be both made under uniform conditions and that reflect the biological diversity of a myriad individual experiences with PD. Such widespread availability of these cells could allow researchers to conduct proof of concept trials on iPS neurons to better understand the effectiveness of a treatment in PD populations or sub-populations before even going to the clinic, potentially saving time and money in the search for novel treatments.
ďItís going to take a concentrated effort for iPS cells to have a measureable impact on finding new drugs for heterogenous diseases like PD,Ē she says.
ďAnd itís here that MJFF is already playing a critical, catalytic role. By bringing the right players to the same table, researchers from academia and industry are discussing how we can best work together toward translating this novel research into practical treatments.Ē