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Protein misfolding is a unifying theme in common neurodegenerative diseases

Neurodegenerative diseases include common diseases like Alzheimer’s and Parkinson’s and rare diseases like Multiple System Atrophy (MSA), progressive supranuclear palsy (PSP) and cerebellar ataxias. These diseases are caused when cells of the brain (“neurons”) are gummed up  by abnormally folded and clumped up proteins. Unlike many other cells in the body, neurons mostly do not divide or renew themselves. That’s why the brain is especially vulnerable to the toxic effects of these  proteins. When neurons die under this “protein stress”, patients lose critical brain functions. In the case of Alzheimer’s disease, memories are taken away and dementia results. In the case of Parkinson’s, MSA, PSP and the ataxias, the ability to control movements – walking, feeding, writing, speaking and swallowing – is taken away. Unfortunately we do not have a single drug or therapy that can reverse the effects of protein misfolding in any of these neurodegenerative diseases. Neurodegeneration is currently unpreventable, unstoppable and irreversible.

Stem cell approaches promise to transform the understanding and treatment of neurodegeneration 

One of the significant challenges to brain disease research has been an inability for us to obtain brain material (or “tissue”) when patients need us most: when they are alive and in the early stages of a disease. Unlike other diseases like cancer, we cannot obtain brain biopsies that provide tissue to inform us of diagnosis and therapy for neurodegenerative disease. So for 100 years or so we have been working with brain tissue obtained after our patients have passed away. Fortunately, revolutionary advances in stem cell technology are enabling us to do better. We can now take a small piece of skin from a patient and convert the skin cells into stem cells (so-called “induced pluripotent stem cells” or iPS cells). From these stem cells we can make any tissue in the body, including brain cells. So, for the first time, we can observe the abnormalities of these diseases develop “in a dish.”  In 2013, we identified abnormalities that result from protein misfolding in stem cell-derived neurons from Parkinson’s disease patients. More importantly, we showed that such abnormalities could be reversed by manipulating patient genes (“genome editing”) or exposing the cells to drug-like molecules. Our work was published in back-to-back papers in the journal Science.

Stem cell approaches for multiple system atrophy, Parkinson’s disease and related disorders

We would like to now extend these efforts to other neurodegenerative diseases, with an initial focus on MSA. MSA involves the misfolding of the same protein that has been implicated in Parkinson’s disease so we have every reason to believe that our Parkinson’s findings might help MSA patients. Unlike Parkinson’s, however, for MSA we have far less understanding of the genes that cause it. That makes it much harder to understand and to study. We aim to create a national stem cell bank for patients with these diseases so we can better understand and treat this devastating disease.

We are indebted to the patients that have generously donated their stem cells and indeed their brains for our research. We are honored to have their trust in carrying this mission forward and finding treatments that have so far eluded us for these devastating diseases.

Based on our previous bench research, we are engaging in clinical studies to advance biomarker and treatment development. See the MyTrail Clinical Trials link to learn more about our approaches in precision medicine for degenerative movement disorders. See also our current clinical research and trial opportunities.
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