Can We Repair the Brain? The Promise of Stem Cell Technologies for Treating Parkinson's Disease

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Can We Repair the Brain? The Promise of Stem Cell Technologies for Treating Parkinson's Disease

JPD article news
Despite challenges, new advances in stem cell biology and genetic engineering show potential for better cell replacement therapies, say experts in a special supplement to JPD

Amsterdam, NL – Cell replacement may play an increasing role in alleviating the motor symptoms of Parkinson's disease (PD) in future. Writing in an open access special supplement to the Journal of Parkinson's Disease, experts describe how newly developed stem cell technologies could be used to treat the disease and discuss the great promise, as well as the significant challenges, of stem cell treatment.

The most common PD treatment today is based on enhancing the activity of the nigro-striatal pathway in the brain with dopamine-modulating therapies, thereby increasing striatal dopamine levels and improving motor impairment associated with the disease. However, this treatment has significant long-term limitations and side effects. Stem cell technologies show promise for treating PD and may play an increasing role in alleviating at least the motor symptoms, if not others, in the decades to come.

"We are in desperate need of a better way of helping people with PD. It is on the increase worldwide. There is still no cure, and medications only go part way to fully treat incoordination and movement problems," explained co-authors Claire Henchcliffe, MD, DPhil, from the Department of Neurology, Weill Cornell Medical College, and Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; and Malin Parmar, PhD, from the Wallenberg Neuroscience Center and Lund Stem Cell Center, Lund University, Lund, Sweden. "If successful, using stem cells as a source of transplantable dopamine-producing nerve cells could revolutionize care of the PD patient in the future. A single surgery could potentially provide a transplant that would last throughout a patient’s lifespan, reducing or altogether avoiding the need for dopamine-based medications."

The authors have analyzed how newly developed stem cell technologies could be used to treat PD, and how clinical researchers are moving very quickly to translate this technology to early clinical trials. In the past, most transplantation studies in PD used human cells from aborted embryos. While these transplants could survive and function for many years, there were scientific and ethical issues: fetal cells are in limited supply, and they are highly variable and hard to quality control. Only some patients benefited, and some developed side effects from the grafts, such as uncontrollable movements called dyskinesias.

Recent strides in stem cell technology mean that quality, consistency, activity, and safety can be assured, and that it is possible to grow essentially unlimited amounts of dopamine-producing nerve cells in the laboratory for transplantation. This approach is now rapidly moving into initial testing in clinical trials. The choice of starting material has also expanded with the availability of multiple human embryonic stem cell lines, as well as the possibilities for producing induced pluripotent cells, or neuronal cells from a patient's own blood or skin cells. The first systematic clinical transplantation trials using pluripotent stem cells as donor tissue were initiated in Japan in 2018.

Sections of rat brain transplanted with human cells in a preclinical model of PD are being prepared for analysis

"We are moving into a very exciting era for stem cell therapy," commented Dr. Parmar. "The first-generation cells are now being trialed and new advances in stem cell biology and genetic engineering promise even better cells and therapies in the future. There is a long road ahead in demonstrating how well stem cell-based reparative therapies will work, and much to understand about what, where, and how to deliver the cells, and to whom. But the massive strides in technology over recent years make it tempting to speculate that cell replacement may play an increasing role in alleviating at least the motor symptoms, if not others, in the decades to come."

"With several research groups, including our own centers, quickly moving towards testing of stem cell therapies for PD, there is not only a drive to improve what is possible for our patients, but also a realization that our best chance is harmonizing efforts across groups," added Dr. Henchcliffe. "Right now, we are just talking about the first logical step in using cell therapies in PD. Importantly, it could open the way to being able to engineer the cells to provide superior treatment, possibly using different types of cells to treat different symptoms of PD like movement problems and memory loss."

"This approach to brain repair in PD definitely has major potential, and the coming two decades might also see even greater advances in stem cell engineering with stem cells that are tailor-made for specific patients or patient groups," commented Patrik Brundin, MD, PhD, Van Andel Research Institute, Grand Rapids, MI, USA, and J. William Langston, MD, Stanford Udall Center, Department of Pathology, Stanford University, Palo Alto, CA, USA, Editors-in-Chief of the Journal of Parkinson's Disease. "At the same time, there are several biological, practical, and commercial hurdles that need circumventing for this to become a routine therapy."

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NOTES TO EDITORS
Full open access study: "Repairing the Brain: Cell Replacement Using Stem Cell-Based Technologies" by Claire Henchcliffe and Malin Parmar (DOI: 10.3233/JPD-181488) published in the Journal of Parkinson's Disease, Volume 8, Supplement 1 by IOS Press. It is openly available at content.iospress.com/articles/journal-of-parkinsons-disease/jpd181488.

Claire Henchcliffe receives funding from the C.V. Starr Foundation and the New York State Department of Health / Empire State Stem Cell Board. Malin Parmar receives support from the New York Stem Cell Foundation, European Research Council, Eurostars, Swedish Research Council, Swedish Parkinson Foundation, and Swedish Brain Foundation.

Contacts
For additional information, contact Diana Murray, IOS Press (+1 718-640-5678 or d.murray@iospress.com). Journalists wishing to interview the authors should contact either Claire Henchcliffe (clh2007@med.cornell.edu) or Malin Parmar (malin.parmar@med.lu.se).

About this Supplement to Journal of Parkinson's Disease
The Journal of Parkinson’s Disease published a special issue in 2017 to commemorate the 200th anniversary of James Parkinson’s "Essay on the Shaking Palsy," and we highlighted eight of the most important advances in Parkinson’s research over the past 60 years. As we were working on that special issue, we commented on how the pace of Parkinson's research has accelerated remarkably. We speculated that there would be more advances in the treatment and care of Parkinson's disease during the coming 20 years than were evident during the preceding 200 years. Thus, the idea of a collection of short, forward-looking, and visionary articles was born. Eventually, we identified 19 topics for articles, and we are very excited about the outcome. In 1964 Bob Dylan sang "The Times They Are a-Changin';" this special supplement clearly shows that the field of Parkinson's is no exception. This new special issue, published as a supplement, is openly available at content.iospress.com/journals/journal-of-parkinsons-disease/8/s1 or via the link tiny.cc/JPD20.

About Journal of Parkinson’s Disease
Launched in 2011, the Journal of Parkinson's Disease (JPD) is dedicated to providing an open forum for original research in basic science, translational research and clinical medicine that will expedite our fundamental understanding and improve treatment of Parkinson’s disease. The journal is international and multidisciplinary and aims to promote progress in the epidemiology, etiology, genetics, molecular correlates, pathogenesis, pharmacology, psychology, diagnosis and treatment of Parkinson's disease. JPD publishes research reports, reviews, short communications, and letters-to-the-editor and offers very rapid publication and an affordable open access option. journalofparkinsonsdisease.com

About IOS Press
IOS Press is headquartered in Amsterdam with satellite offices in the USA, Germany, India and China and serves the information needs of scientific and medical communities worldwide. IOS Press now publishes over 100 international journals and about 75 book titles each year on subjects ranging from computer sciences and mathematics to medicine and the natural sciences. iospress.com