Gift for ALS Research
Fuel for a new collaboration sparked by Steven Finkbeiner, PhD
Steven Finkbeiner is Senior Investigator and Associate Director of the Gladstone Institutes of Neurological Disease and Professor of Neurology and Physiology at the University of California, San Francisco. He is also the newest research scientist with the Robert Packard Center for ALS Research at Johns Hopkins. Finkbeiner joined Packard after giving a seminar at their monthly meeting on the use of small molecules in stem cell models of ALS to determine what goes wrong in motor neurons to cause disease, and how this can potentially be repaired.
Finkbeiner’s new collaboration with the Packard group was made possible by a generous gift from the William H. Adams Foundation with the help of Mr. Steven Merrill, who serves on both the William Adams Foundation and UCSF Foundation boards. Named for prominent Bay Area business leader, Bill Adams, who lost his battle with ALS in 2010, the Adams Foundation has been instrumental in providing financial support for the Packard Center’s groundbreaking research efforts for the past thirteen years.
“Collaboration is critical for several reasons," Finkbeiner says. "First, neurodegenerative diseases are really hard problems to solve and no single group can do it alone. You need a team of people with different skill sets and perspectives and a genuine appreciation of the collaborative process. Second, the resources required to solve these problems are substantial. I have found that collaborations between groups – including donors, biotechnology and pharmaceutical companies – are key to making a meaningful attempt to develop therapies. Research groups like ours in the Packard Center provide the deep biological understanding of disease that makes it possible to develop therapies rationally.”
“We are proud of our continued support of the great work being done by the Packard Center, and are especially proud that we were able to help fund this project with Dr. Finkbeiner and the Gladstone Institutes,” says Ellen Adams, president of the William H. Adams Foundation For ALS Research. “I can think of no better way of honoring Bill’s legacy then funding this crucial project in the Bay Area.”
Finkbeiner is known best for his development of a technique known as robot microscopy. Cells are sensitive to factors like heat, so viewing cultured cells under a microscope often meant the cells died. Robotic microscopy, however, lets scientists view the same cells over time, revealing how they are affected by mutant proteins. “It lets us follow individual brain cells in a culture dish much the same way we follow people in clinical trials,” he said. By following individual brain cells, researchers like Finkbeiner can track what happens as genes are turned on and proteins are synthesized.
Finkbeiner’s robotic microscope led to one of the first studies that showed how TDP-43 could cause ALS symptoms in an animal model. In a paper published in the Journal of Neuroscience, Finkbeiner and colleagues showed that mutant TDP-43 was found in the cytoplasm of cells, rather than the nucleus. By tracking these cells over time, they could show that the amount of TDP-43 in the cytoplasm was related to cell death.
More recently, Finkbeiner has begun creating new induced pluripotent stem cell lines (iPSCs) from skin and blood samples from patients with neurodegenerative diseases like ALS. He is then transforming these stem cells into brain cells, which allows him to deepen our understanding of ALS, as well as develop new therapeutics. In 2012, he published a paper in the Proceedings of the National Academy of Sciences (PNAS) that showed motor neurons derived from iPSCs from ALS patients carrying a TDP-43 mutation were remarkably similar to motor neurons from these patients. These results showed that these cell cultures could be a good model for what was happening in ALS patients.
Earlier this year, Finkbeiner and colleagues published a separate study in PNAS that used iPSCs to show how astrocytes carrying a TDP-43 mutation did not harm healthy motor neurons that were living in the same cell culture. The results are important, the researchers say, because they show the opposite effect of SOD1 mutations (astrocytes with mutant SOD1 did cause the death of co-cultured, non-mutant motor neurons) and provide a better understanding of how different gene mutations can lead to ALS pathology.
His collaborations with Packard scientists have already begun. Shortly after he gave his June seminar, several Packard researchers approached him about working together - a proposal he has enthusiastically endorsed. He is also beginning to look more closely at some potential therapeutic targets for ALS. “We have some very exciting initial results, and we will develop these further. If the results continue to look promising, we will take steps to develop drugs based on this target to see if they could become therapies for ALS,” Finkbeiner said.