Disease in a dish

NYSCF research programs skin cells into Alzheimer’s disease brain cells

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NEW YORK—Alzheimer's disease research is facing a new avenueof research options, as some of the latest research to come out of the New YorkStem Cell Foundation (NYSCF) is a cell-based model of the neurodegenerativedisease. A team of researchers led by Dr. Scott Noggle, a NYSCF-Charles EvansSenior Research Fellow for Alzheimer's disease, created the models byreprogramming skin cells from Alzheimer's patients to become brain cellsaffected 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 amyotrophiclateral sclerosis (ALS), also known as Lou Gehrig's disease, four years ago.That work, which represented the first patient-specific stem cells created forany disease, was the foundation for the Alzheimer's model.
"Patient-derived AD cells will prove invaluable for futureresearch advances, as they already have with patient-derived ALS cells," SusanSolomon, CEO of the NYSCF, said in a press release. "They will be a criticaltool in the drug discovery process, as potential drugs could be tested directlyon these cells. Although research on animals has provided valuable insight intoAD, we aren't mice, and animals don't properly reflect the features of the diseasewe are trying to cure. As we work to find new drugs and treatments, ourresearch should focus on actual human sufferers of Alzheimer's disease."
The Alzheimer's models were created by programming skin cellsamples from 12 patients with early-onset Alzheimer's and from healthy,genetically related individuals. The samples were programmed into inducedpluripotent stem (iPS) cells, which are capable of differentiation into anytype of cell. The iPS cells were then used to create cholinergic basalforebrain neurons, the brain cells affected by the disease, and the resultingcells summarize the features and cellular-level function of Alzheimer'spatients.
The work was done in collaboration with Dr. Sam Gandy, aninternational expert in Alzheimer's pathology at Mount Sinai School ofMedicine. Dr. Steve Chang, vice president of research and development at theNYSCF, notes that "both our foundation and the research groups we partner withhave a formal understanding of the work we undertake (with Mount Sinai). NYSCFhas had great, productive relationships with Mount Sinai."
Preliminary results from the Alzheimer's model have revealedthat Alzheimer's neurons produce more of the toxic form of beta amyloid thandisease-free neurons.
"While animal models, like mice, have been invaluable toincreasing our understanding of the features of diseases like Alzheimer's, theyfail to fully recapitulate what happens on the cellular level," says Chang. "Wecan reprogram stem cells to the actual cell types involved in diseases likeAlzheimer's."
Chang says this work "can—and will—be translated to otherdiseases like Parkinson's and schizophrenia," noting that NYSCF researchers arealready working to create cell models from skin and blood samples ofParkinson'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 refiningand stepping up output of the Alzheimer's stem cell lines, says Chang.
"In the future, these disease models will be used fordiscovery of new therapeutics. We can test the most promising drug compounds onthe affected cells, and see, in vitro,what is a viable drug candidate and what likely will result in a dead-end. Thiscould completely streamline the research and development process for drugs andtherapies," he says. "We have to date derived stem cell lines from Alzheimer'spatients with a genetic predisposition to the disease. We are going to begin deriving large numbersof stem cell lines from patients with sporadic forms of Alzheimer's diseasethat will give us a better understanding of disease processes."
The stem cell field is still young, says Chang, but "hugestrides" 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' cellscould be tested, which Chang calls "the promise of personalizedmedicine—crafting treatments tailored to individuals' specific genetic types."
"Stem cell research is at the very forefront of regenerativemedicine, and it holds a very important place in the development of cures for majordiseases," says Chang.

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