Readings
ClinicalTrials.gov. U.S. National Institutes of Health. http://clinicaltrials.gov (Accessed June 2014).
Mikol, Daniel D., Frederik Barkhof, Peter Chang, Patricia K. Coyle, Douglas R. Jeffery, Steven R. Schwid, Bettina Stubinski, Bernard M. J. Uitdehaag, on behalf of the REGARD study group. “Comparison of Subcutaneous Interferon Beta-1a With Glatiramer Acetate on Patients With Relapsing Multiple Sclerosis (The Rebif Vs Glatiramer Acetate in Relapsing MS Disease [REGARD] Study): A Multicentre, Randomised, Parallel, Open-Label Trial.” Lancet Neurology, v.7/10 (October 2008).
National Multiple Sclerosis Society. http://www.nationalmssociety.org (Accessed June 2014).
Clinical Trials, U.S.: Parkinson’s Disease
Clinical Trials, U.S.: Parkinson’s Disease
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Clinical Trials, U.S.: Parkinson’s Disease
International Stem Cell Corporation, a California biotechnology company currently developing biomedical products and new stem cell therapies, announced on April 29, 2014, that some behavioral progress has been observed over a six-month period in the preclinical nonhuman primate (NHP) study of Parkinson’s disease (PD), which includes 18 primates, all exposed to neurotoxin MPTP. These results are particularly remarkable and promising as they mean, for patients, greater decrease in the severity of their symptoms. The detailed data will be introduced at the upcoming 66th American Academy of Neurology Annual Meeting in Philadelphia.
Parkinson’s disease is a degenerative condition of the central nervous system (CNS), in which motor symptoms are caused by the death of cells located in the midbrain that are responsible for the production of dopamine. Beyond cell death, the actual cause for PD has proven elusive. In the first phase of the disease, the most apparent symptoms are related to movements: gait, rigidity, tremors, trouble walking and moving. In the subsequent phases, behavioral issues and impairment in thinking usually occur, promptly followed by dementia. Depression is known to be the most frequent psychiatric symptom. Parkinson’s disease is more prevalent in individuals over the age of 50.
According to the Parkinson’s Disease Foundation, about seven to 10 million people worldwide live with Parkinson’s disease. Of that population, 1 million reside in the United States, where the cost of the disease is estimated, in this country alone, at $25 billion per year.
Parkinson’s Disease Treatment
To date, there is no cure for Parkinson’s disease. The different therapies available are targeted at treating the disease symptoms, which may vary from patient to patient. This explains why there is no standard or “preferred” treatment for PD. Treatment options currently include medications, lifestyle changes, and, eventually, surgical therapy.
However, despite the efficacy of these therapies at managing the early motor symptoms of the disease through the use of dopamine agonists and levodopa, such treatments have proven insufficient in stemming its progress. The disease progression results in the loss of dopaminergic neurons, and the treatment eventually becomes ineffective at treating even those symptoms, causing instead complications such as dyskinesia (difficulty in making voluntary movements).
Within that context, stem cell research presents a good prospect for the treatment of Parkinson’s disease, especially if researchers succeed in creating dopamine-producing cells from stem cells.
Stem cell therapy uses stem cells to treat patients and prevent the occurrence of disease. Outside of bone marrow transplant, no stem cell therapies are currently largely used. However, research is urgently trying to implement stem cell treatments for neurodegenerative conditions such as heart disease, diabetes, and Parkinson’s disease, and this in spite of the controversy surrounding human cloning or the issue of abortion.
One of the promising options to improve dopaminergic dysfunction in Parkinson’s disease is neural transplantation. The strategy behind this process is to graft cells capable of generating dopamine into the denervated striatum, thus restoring not only function but neurotransmission. In this context, fetal mesencephalic tissue as a source of dopaminergic neurons could well represent a therapeutic alternative to cell transplantation therapy in human patients.
Despite the hope that stem cell therapy research brings to this field, several limitations still impact the use of human fetal tissue transplantation: ethical concerns, tissue variability, inability to obtain significant enough amounts of tissue, and lack of scalability. Consequently, it proves very hard to monitor the identity and effectiveness of these cells, which, if not properly controlled, could threaten both treatment efficacy and patient safety. Researchers and clinicians who favor stem cell therapy are deeply convinced that human neural stem cells constitute a reliable source of dopaminergic neurons for Parkinson’s disease. They believe that these neurons could safely treat a large number of patients both inside and outside the United States.
Current Clinical Trials: Parkinson’s Disease
Early attempts to treat PD with stem cell therapy were not successful. However, despite still being in the beginning stages of development, stem cell therapy has made a lot of progress. In this context, the field of embryonic stem cells seems particularly promising. Several neurogeneration programs like those of Johns Hopkins University, or the New York Stem Cell Foundation, and many others are furthering their research on ways to generate dopamine-producing neurons in the lab environment. Researchers are additionally working on induced pluripotent stem (iPS) cells, which were discovered back in 2007, in the hope of making them one day the treatment of choice for patients with Parkinson’s disease. The particularity of iPS cells is that they come from adults and have the capability, like embryonic stem cells (ES), to develop into other types of cells. Scientists “reprogram” a mature cell into a cell resembling that of an embryo and use the converted cell as a disease model for new drug screening, knowing that such cells carry the potential of being used in cell replacement therapies for patients.
These past years, the work performed in neurodegenerative diseases involving animal models has proven that the progression of the disease can be slowed down. However, the positive outcomes related to this progress have not been reflected in human models yet. Researcher Lorenz Studer and his team have recently succeeded in creating very effective dopamine-producing neurons from human embryonic stem cells. After transplanting the neurons into the brains of mice and rats with Parkinson’s disease, the research team noticed that the cells did not proliferate in an abnormal way and, instead, improved some of the existing symptoms. The neurons were transplanted into monkeys, and it was shown that they could survive in larger animals.
There is still much progress to be made before stem cell replacement therapy for Parkinson’s disease becomes a reality. Neurons would need to be produced in sufficient quantity to be effective, and cells would need to be deemed totally safe. Researchers and clinicians pin their hope on being able to start initial clinical trials by late 2014 or early 2015. Significant funding resources—at both state and federal levels in the United States—have been deployed to encourage research.
Morenike Trenou
Independent Scholar
See Also: Embryonic Stem Cells, Methods to Produce; Immune Disorders; Parkinson’s Disease; Parkinson’s
