Alzheimer's and Regenerative Medicine

Alzheimer's and Regenerative Medicine

Overview

Alzheimer’s Disease (AD) is the most common form of dementia (the general term for loss of memory and intellectual abilities) that attacks neurons in the brain, resulting in memory loss, cognitive impairment and behavioral changes. The disease disrupts the brain’s communication network, eventually destroying neuronal synapses and killing neurons altogether. There are an estimated 5.4 million Americans suffering from the disease, and the prevalence doubles every five years beyond the age of 65.1 As of 2010, there are 35.6 million people living with the disease, and it is the sixth-leading cause of death in the United States.2 While the majority of people with the disease are 65 and older, about five percent of the people afflicted have early-onset Alzheimer’s which can occur when a patient is in their 40s and 50s.3 AD is not a part of the normal aging process. Symptoms get progressively worse over time and can include confusion with time and place, struggles to complete familiar tasks and changes in mood and personality.

The disease is characterized by two types of abnormal lesions that build up around neurons in the brain including beta-amyloid plaques (clumps of protein fragments and cellular material) and neurofibrillary tangles (insoluble twisted fibers composed of the Tau protein). It is not certain whether these lesions cause disease or are a byproduct of it. As stated earlier, there is no cure for AD and the disease can only be officially confirmed by autopsy after a patient’s death.4 There are currently five FDA-approved Alzheimer’s drugs that treat the symptoms of AD, however, they do not treat the underlying causes of the disease.5

Alzheimer’s Disease and Regenerative Medicine

The creation of disease models through cellular reprogramming of patient-specific cells has allowed scientists to create human disease models of AD to study the disease in controlled laboratory conditions. Cellular reprogramming is a process when scientists reverse fully differentiated, mature cells into an embryonic state, i.e., creating disease induced pluripotent stem cell lines.

Several ARM members are highly involved in these new efforts. Scientists at The New York Stem Cell Foundation lab have developed a cell-based model of Alzheimer’s disease. In this initiative led by Scott Noggle, PhD, the researchers reprogrammed cells of early-onset patients into induced pluripotent stem cells to create cholinergic basal forebrain neurons (the cells affected in Alzheimer’s). These cells demonstrate the features of the disease on a cellular level, creating a viable disease model that will be critical for drug discovery and testing. Preliminary results have demonstrated differences in cellular function in patients. Alzheimer’s neurons produced more of the toxic form of beta amyloid, the protein found in amyloid plaques, than healthy neurons.6

iPierian has also created disease models from patient-derived pluripotent stem cells to advance their novel drug development programs. After using the disease models to validate the therapeutic targets and mechanisms of disease, they hope to move toward using monoclonal antibodies to treat AD (and other neurodegenerative diseases) by targeting the Tau protein.7iPierian is aiming to start human trials with their potential drugs in 2014.8

The California Institute for Regenerative Medicine (CIRM), California’s stem cell agency, is supporting the development of technologies to treat AD which includes eleven research grants.9 CIRM recently awarded StemCells, Inc. a $20 million boost for the company to collaborate with UC-Irvine’s Sue & Bill Gross Stem Cell Research Center’s neurobiologists and the Institute for Memory Impairments and Neurological Disorders (UCI MIND) to advance the company’s human neural stem cell technology in Alzheimer’s. Researchers have already reported that StemCells, Inc.’s neural stem cells restored memory and enhanced synaptic function in two animal models similar to AD. It is believed these cells provide growth factors that protect the neurons from degeneration.10

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1Alzheimer’s Foundation of America, “About Alzheimer’s: Statistics,” 2013, available at www.alzfdn.org/AboutAlzheimers/statistics.html
2World Alzheimer Report 2010: The Global Economic Impact of Dementia, available at www.alz.co.uk/research/files/WorldAlzheimerReport2010.pdf (published by Alzheimer’s Disease International, June 2011)
3Alzheimer’s Association, “What is Alzheimer’s?”, 2013, available at www.alz.org/alzheimers_disease_what_is_alzheimers.asp
4Alzheimer’s Foundation of America, “About Alzheimer’s: Definition of Alzheimer’s,” 2013, available at www.alzfdn.org/AboutAlzheimers/definition.html
5Alzheimer’s Association, “Science & Progress: Treatment Horizon,” 2013, Alzheimer’s Association website, www.alz.org/research/science/alzheimers_treatment_horizon.asp
6California Institute for Regenerative Medicine (CIRM), “Alzheimer’s Disease Fact Sheet,” CIRM website, www.cirm.ca.gov/Alzheimers_Disease_Facts
7“New York Stem Cell Foundation (NYSCF) Scientists Featured At The Alzheimer’s Association International Conference for New Model of Alzheimer’s Disease (AD),” NYSCF press release, July 16, 2012, on the NYSCF website, www.nyscf.org/pdfs/NYSCF_PR_Alzheimers2.pdf
8“iPierian Advances Monoclonal Antibody Drug Development Programs Targeting Tau Protein and the Complement System for the Treatment of Neurodegenerative Diseases,” iPierian press release, May 21, 2012, on the iPierian website, http://www.ipierian.com/drupal/news-events/press-releases/2012/05/ipieri...
9Ron Leuty,“iPierian turns its stem cell technology on Alzheimer’s, antibody drugs,” San Francisco Business Times, May 21, 2012, available at www.bizjournals.com/sanfrancisco/blog/biotech/2012/05/ipieiran-ips-stem-...
10California Institute for Regenerative Medicine (CIRM), “Alzheimer’s Disease Fact Sheet,” CIRM website, www.cirm.ca.gov/Alzheimers_Disease_Facts
11“State stem cell research funding agency awards $37.3 million to aid UC Irvine efforts,” University of California, Irvine press release, September 6, 2012, on the UC Irvine Today website, http://today.uci.edu/news/2012/09/nr_cirmklassen_120906.php
12Alzheimer’s Foundation of America, “About Alzheimer’s: Cost,” 2013, available at www.alzfdn.org/AboutAlzheimers/cost.html
132013 Alzheimer’s Disease Facts and Figures Report available at www.alz.org/alzheimers_disease_facts_and_figures.asp#quickfacts (published by Alzheimer’s Association, 2013)