Cell replacement therapies may help treat Parkinson's disease

Cell replacement therapies may help alleviate the symptoms of Parkinson's disease, a progressive disorder that currently has no cure, scientists say. 

According to a study published in the Journal of Parkinson's Disease, newly developed stem cell technologies could be used to treat the disease. The most common Parkinson's disease 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 Parkinson's Disease 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 Parkinson's disease. It is on the increase worldwide. There is still no cure, and medications only go part way to fully treat in co-ordination and movement problems," said Claire Henchcliffe, from Weill Cornell Medical College in the US. "If successful, using stem cells as a source of transplantable dopamine-producing nerve cells could revolutionize care of the Parkinson's disease patient in the future," said Malin Parmar, from Lund University in Sweden. 

"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," said Parmar. Researchers have analysed how newly developed stem cell technologies could be used to treat Parkinson's disease, 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 -- foetal 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, researchers said. 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. 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, researchers said. "With several research groups, including our own centres, quickly moving towards testing of stem cell therapies for Parkinson's disease, there is not only a drive to improve what is possible for our patients, but also a realisation that our best chance is harmonising efforts across groups," said Henchcliffe. 

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NHLBI stem cell consortium provides new insights into genetics of heart disease, other conditions

NIH-funded scientists has published the first studies using the largest, most diverse stem cell collection of its kind ever made available to researchers. The results provide fresh insights into the genetic underpinnings of common conditions such as cardiovascular disease, high blood pressure, diabetes, and sickle cell disease, which take a heavy toll on American lives and resources.

In the future, discoveries from these studies of adult stem cells could lead to new ways to diagnose and treat disease, the researchers say. The first 11 studies resulting from this collaborative effort from multiple US institutions appear in the journals Cell Stem Cell, Stem Cell Reports, and EBioMedicine, which are published by Cell Press.

In 2011, the National Heart, Lung, Blood Institute (NHLBI), part of NIH, convened its Next Generation Genetic Association Studies (NextGen) Consortium with the goal of using induced pluripotent stem cells (link is external) (iPS cells) to better understand how complex genetic changes affect heart, lung, and blood cells. More than 1,000 iPS cell lines were obtained from more than 1,000 volunteers of different genders and ethnic backgrounds, making it one of the one of the most diverse stem cell collections ever studied. That diversity, the researchers note, ultimately will prove useful in helping reduce health disparities based on gender and ethnicity.

Though still in their early stages, the NextGen studies are already beginning to produce results. For example, one research group created a library of iPS cells from a geographically- and ethnically-diverse group of people with sickle cell disease. This well-characterized stem cell library could provide the basis for improved pre-clinical drug development for sickle cell disease, the study’s researchers say.

In addition to sickle cell disease, the cell lines from NextGen will prove helpful for studying other complex diseases, particularly cardiovascular disease. In the future, researchers hope to make these stem cell lines available for other researchers to study worldwide.

Cashell Jaquish, Ph.D., program director for the NHLBI’s NextGen Consortium, is available to comment on the findings and implications of this research.

About the National Heart, Lung, and Blood Institute (NHLBI): NHLBI, a part of the National Institutes of Health (NIH), plans, conducts, and supports research related to the causes, prevention, diagnosis, and treatment of heart, blood vessel, lung, and blood diseases; and sleep disorders. The Institute also administers national health education campaigns on women and heart disease, healthy weight for children, and other topics. 

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Diabetes: Breaktrhough Achieved via Inserted Device to Produce Insulin Inside Body

If a father happens to be a scientist and his daughter afflicted with Diabetes 1 from birth, then there is no way he could sleep peacefully unless he finds a solution to it and that’s what happend with Harvard researcher Doug Melton, who had spent 23 years in his quest to fine one to develop a device that can insert a device to produce millions of beta cells inside the body.

His life-long dedication to find treatment for type 1 diabetes that hits about 3 million Americans costing about $15 billion in treatment finally led him to explore stem-cell production of insulin in massive quantity from the human insulin-producing beta cells like any normally functioning beta cells.

Type 1 diabetes is an autoimmune metabolic condition in which the body kills off all the pancreatic beta cells that produce the insulin needed for glucose regulation in the body. Thus the final pre-clinical step in the development of a treatment involves protecting from immune system attack the approximately 150 million cells that would have to be transplanted into each patient being treated. And Melton succeeded developing an implantation device to protect the cells.

He was helped in his research by Daniel G. Anderson, the Samuel A. Goldblith Professor of Applied Biology, Associate Professor in the Department of Chemical Engineering, the Institute of Medical Engineering and Science, and the Koch Institute at MIT. Melton also expressed gratitude to both the Juvenile Diabetes Research Foundation and the Helmsley Trust, saying “their support has been essential.”

While diabetics can keep their glucose metabolism under general control by injecting insulin multiple times a day, that does not provide the kind of fine tuning necessary to control metabolism, and it leads to devastating complications from blindness to loss of limbs.

Even 10 percent of the more than 26 million Americans living with type 2 diabetes are also dependent upon insulin injections, and would presumably be candidates for beta cell transplants, Melton said.

Now, he hopes to have human transplantation trials using the cells within a few years. “We are now just one pre-clinical step away from the finish line,” said Melton, whose daughter Emma has type 1 diabetes.

His work will be published in the journal Cell, with Felicia W. Pagliuca, Jeff Millman, and Mads Gurtler of Melton’s lab as co-first authors on the Cell paper.

The stem cell-derived beta cells are presently undergoing trials in animal models, including non-human primates, Melton said.

Elaine Fuchs at Rockefeller University hailed the research outcome. “For decades, researchers have tried to generate human pancreatic beta cells that could be cultured and passaged long term under conditions where they produce insulin. Melton and his colleagues have now overcome this hurdle and opened the door for drug discovery and transplantation therapy in diabetes,” Fuchs said.

Jose Oberholtzer, M.D., Associate Professor of Surgery, Endocrinology and Diabetes, and Bioengineering at the University of Illinois at Chicago, said, “Doug Melton has put in a life-time of hard work in finding a way of generating human islet cells in vitro. He made it. This is a phenomenal accomplishment.”

Cell transplantation as a treatment for diabetes is still essentially experimental, uses cells from cadavers, requires the use of powerful immunosuppressive drugs, and has been available to only a very small number of patients.

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