Please could you tell us a little bit about Parkinson’s disease and who it affects?
Parkinson’s disease is a disorder which usually affects people in their 60’s and older. It is caused by the loss of dopamine neurons in the brain leading to rigidity, slowness of movement, tremor, problems with balance and so forth.
It was reported that your recent research into treatments for Parkinson’s disease used adult stem cells. Please could you explain what adult stem cells are?
We didn’t actually use adult stem cells; we used induced pluripotent stem (IPS) cells. We took skin cells from patients without Parkinson’s disease and from those with different forms of Parkinson’s disease. Then we converted them to inducible pluripotent stem cells using established protocol.
These inducible pluripotent stem cells have almost all the properties of embryonic stem cells, in that you can turn them in to any cells that you want in the body. In this case we turned them into neurons; specifically we turned them into dopamine neurons that degenerate in Parkinson’s disease.
How could you be sure that the stem cell-generated neurons would behave like dopamine brain cells?
We relied on the work of other investigators. There has been a tremendous amount of interest in the field about how you turn these IPS cells, or embryonic stem cells, into real life dopamine neurons.
We used protocols that have already been established. But in our cultures we also validated that what we created were valid dopamine neuron cells.
How did your research originate?
When the IPS technology was first published it seemed an obvious thing to do to take skin biopsies from patients with Parkinson’s disease so that you could model the disease in human dopamine neurons. This is something we’ve never been able to do before. It was almost a no-brainer once the technology had been developed.
What did your research show?
For this paper we made IPS cells from patients with LRKK2 and PINK1 mutations and showed that these mutations lead to mitochondrial defects, such as defects in mitochondrial respiration and defects in mitochondrial mobility.
This predisposes those dopamine neurons to stresses that have been linked to Parkinson’s disease: agents that interfere with mitochondrial function; agents that enhance reactive oxygen species – free radicals and so forth.
Finally, we looked at drugs that are known to inhibit cell death processes in animal models and showed that these drugs prevented stress induced damage to the dopamine neurons
How important is timing in the treatment of Parkinson’s disease?
It may be everything with regards to disease modifying therapy. The community has documented a number of trials which have either failed or not given definitive answers. And so, either our targets aren’t any good; or, based on our results, I suggest that we are not treating patients early enough.
How do you see our understanding of Parkinson’s disease progressing?
I think it will progress at quite a rapid rate. We are understanding the underlying molecular pathogenesis of Parkinson’s disease more and more every day and that is going to lead to new drugs and new treatments that we can test in IPS cells and ultimately in patients.
How will your research impact on the treatment of Parkinson’s disease?
I don’t know whether it will have any immediate applications but I think that it will reinforce the notion that, for disease modifying therapy, we are treating patients too late. We really need to treat patients earlier.
We need to come up with ways to identify patients who are destined to get Parkinson’s disease but don’t know it yet.
How do you see the future of treatment of Parkinson’s disease progressing?
I think the future looks quite promising, I think we are going to have agents that we know slow the progression and that modify the disease. I think we are also going to have agents which treat some of the complications of Parkinson’s disease much more effectively.
I think it is really exciting times for doing research into Parkinson’s disease.
Do you have any plans for further research into this field?
We’re going to continue to do IPS cell work. We would actually like to develop a model for dopamine neurons so that you don’t need to apply stresses to get them to die, but they would actually die because they have the mutation.
We’re also trying to understand the functions of these proteins and also identifying new targets.
Where can our readers find more information?
The paper can be found here: http://www.ncbi.nlm.nih.gov/pubmed/22764206
About Ted M. Dawson, MD, PhD
Dr. Dawson is the Leonard and Madlyn Abramson Professor in Neurodegenerative Diseases and Director of the Institute for Cell Engineering at the Johns Hopkins University School of Medicine.
Dr. Dawson’s honors include the Derek Denny-Brown Young Neurological Scholar Award, the Paul Beeson Physician Faculty Scholar Award, and the Santiago Grisolia Medal. He was elected to the Association of American Physicians and he is a Fellow of the American Association for the Advancement of Science. He elucidated the molecular mechanisms by which NO kills neurons through activation of poly [ADP-ribose] (PAR) polymerase (PARP) and release of apoptosis inducing factor (AIF) via PAR polymer and discovered Parthanatos.
Dr. Dawson has been at the forefront of research into the biology and pathobiology of mutant proteins linked to familial Parkinson’s disease. These studies are providing novel opportunities for therapies aimed at preventing the degenerative process of PD and other neurodegenerative disorders.