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Disease in a dish
NEW YORK— Alzheimer's disease research is facing a new avenue of research options, as some of the latest research to come out of the New York Stem Cell Foundation (NYSCF) is a cell-based model of the neurodegenerative disease. A team of researchers led by Dr. Scott Noggle, a NYSCF-Charles Evans Senior Research Fellow for Alzheimer's disease, created the models by reprogramming skin cells from Alzheimer's patients to become brain cells affected by Alzheimer's, enabling for the first time research directly on living, Alzheimer's-afflicted brain cells.
The NYSCF launched a cell-based model for amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, four years ago. That work, which represented the first patient-specific stem cells created for any disease, was the foundation for the Alzheimer's model.
"Patient-derived AD cells will prove invaluable for future research advances, as they already have with patient-derived ALS cells," Susan Solomon, CEO of the NYSCF, said in a press release. "They will be a critical tool in the drug discovery process, as potential drugs could be tested directly on these cells. Although research on animals has provided valuable insight into AD, we aren't mice, and animals don't properly reflect the features of the disease we are trying to cure. As we work to find new drugs and treatments, our research should focus on actual human sufferers of Alzheimer's disease."
The Alzheimer's models were created by programming skin cell samples from 12 patients with early-onset Alzheimer 's and from healthy, genetically related individuals. The samples were programmed into induced pluripotent stem (iPS) cells, which are capable of differentiation into any type of cell. The iPS cells were then used to create cholinergic basal forebrain neurons, the brain cells affected by the disease, and the resulting cells summarize the features and cellular-level function of Alzheimer's patients.
The work was done in collaboration with Dr. Sam Gandy, an international expert in Alzheimer's pathology at Mount Sinai School of Medicine. Dr. Steve Chang, vice president of research and development at the NYSCF, notes that "both our foundation and the research groups we partner with have a formal understanding of the work we undertake (with Mount Sinai). NYSCF has had great, productive relationships with Mount Sinai."
Preliminary results from the Alzheimer's model have revealed that Alzheimer's neurons produce more of the toxic form of beta amyloid than disease-free neurons.
"While animal models, like mice, have been invaluable to increasing our understanding of the features of diseases like Alzheimer's, they fail to fully recapitulate what happens on the cellular level," says Chang. "We can reprogram stem cells to the actual cell types involved in diseases like Alzheimer's."
Chang says this work "can—and will—be translated to other diseases like Parkinson's and schizophrenia," noting that NYSCF researchers are already working to create cell models from skin and blood samples of Parkinson's patients. He adds that the NYSCF laboratory is also creating the "disease-in-a-dish " models for diseases such as diabetes and heart disease.
Moving forward, Noggle and his team will continue refining and stepping up output of the Alzheimer's stem cell lines, says Chang.
"In the future, these disease models will be used for discovery of new therapeutics. We can test the most promising drug compounds on the affected cells, and see, in vitro, what is a viable drug candidate and what likely will result in a dead-end. This could completely streamline the research and development process for drugs and therapies," he says. "We have to date derived stem cell lines from Alzheimer's patients with a genetic predisposition to the disease. We are going to begin deriving large numbers of stem cell lines from patients with sporadic forms of Alzheimer's disease that will give us a better understanding of disease processes."
The stem cell field is still young, says Chang, but "huge strides" are being made. Disease-specific stem cell lines will allow for "clinical trials in a dish" in the future, he adds, in testing drug efficacy, toxicity and side effects on living cells. Even individual patients' cells could be tested, which Chang calls "the promise of personalized medicine—crafting treatments tailored to individuals' specific genetic types."
"Stem cell research is at the very forefront of regenerative medicine, and it holds a very important place in the development of cures for major diseases," says Chang.