SRF: “The fight against forgetting”

NOMIS Distinguished Scientist Tony Wyss-Coray appeared on the Swiss television program, Einstein, which aired on Feb. 15, 2018. The story, “Kampf gegen das Vergessen” (“The fight against forgetting”), addresses the crippling effects of Alzheimer’s disease and highlights Wyss-Coray’s promising research in this direction. Professor of neurology and neurological sciences at Stanford University, Wyss-Coray’s groundbreaking findings suggest that the plasma in our blood directly influences aging. His most recent studies have shown that circulatory factors can modulate neurogenesis, neuroimmunity and cognitive function in mice and that blood-derived factors from young mice or humans can rejuvenate the aging mouse brain.

NOMIS is supporting Wyss-Coray’s continued research into identifying the circulatory factors that influence aging and using those factors to rejuvenate the aging or degenerated brain.

Einstein is a weekly Schweizer Radio und Fernsehen (SRF) newsmagazine.

Salk Institute: “Alzheimer’s drug turns back clock in powerhouse of cell”

Salk researchers have identified the molecular target of J147. The experimental drug is something of a modern elixir of life; it’s been shown to treat Alzheimer’s disease and reverse aging in mice and is almost ready for clinical trials in humans. Now, Salk scientists have solved the puzzle of what, exactly, J147 does. In a paper published January 7, 2018, in the journal Aging Cell, they report that the drug binds to a protein found in mitochondria, the energy-generating powerhouses of cells. In turn, they showed, it makes aging cells, mice and flies appear more youthful.

“This really glues together everything we know about J147 in terms of the link between aging and Alzheimer’s,” says Dave Schubert, head of Salk’s Cellular Neurobiology Laboratory and the senior author on the new paper. “Finding the target of J147 was also absolutely critical in terms of moving forward with clinical trials.”

Schubert’s group developed J147 in 2011, after screening for compounds from plants with an ability to reverse the cellular and molecular signs of aging in the brain. J147 is a modified version of a molecule (curcumin) found in the curry spice turmeric. In the years since, the researchers have shown that the compound reverses memory deficits, potentiates the production of new brain cells, and slows or reverses Alzheimer’s progression in mice. However, they didn’t know how J147 worked at the molecular level.

In the new work, led by Schubert and Salk Research Associate Josh Goldberg, the team used several approaches to home in on what J147 is doing. They identified the molecular target of J147 as a mitochondrial protein called ATP synthase that helps generate ATP—the cell’s energy currency—within mitochondria. They showed that by manipulating its activity, they could protect neuronal cells from multiple toxicities associated with the aging brain. Moreover, ATP synthase has already been shown to control aging in C. elegans worms and flies.

The Salk Institute has been a NOMIS partner since 2008.

Related news
Aging Cell
ScienceDaily

Aging Cell: “The mitochondrial ATP synthase is a shared drug target for aging and dementia”

Scientists at the Salk Institute have published the results of a study in the journal Aging Cell, showing the novel molecular link between aging and dementia through the identification of the molecular target for the Alzheimer’s disease drug J147.

Led by Dave Schubert, head of Salk’s Cellular Neurobiology Laboratory, and Salk Research Associate Josh Goldberg, the team identified the molecular target of J147 as a mitochondrial protein called ATP synthase that helps generate ATP—the cell’s energy currency—within mitochondria. They showed that by manipulating its activity, they could protect neuronal cells from multiple toxicities associated with the aging brain. Moreover, ATP synthase has already been shown to control aging in C. elegans worms and flies. Now, J147 is nearing clinical trials to treat Alzheimer’s disease.

The Salk Institute has been a NOMIS partner since 2008.

Aeon: “‘Let the soul dangle’: how mind-wandering spurs creativity”

In a recent article by Julia Christensen, Guido Giglioni and NOMIS Distinguished Scientist Manos Tsakiris, published in Aeon, the authors suggest that “reverie might help to prime us to think both productively and creatively by somehow cementing our sense of self, drawing body and mind together in a train of thought and biological action.” The authors identify art as a catalyst for letting the mind wander, which in turn induces reflections and emotions and affects the body’s physiology.

Tsakiris is leading the Body and Image in Arts and Sciences (BIAS) project at the Warburg Institute, School of Advanced Study, University of London. BIAS is supported by the NOMIS Foundation.

NZZ: “On the trail of the fountain of youth”

Swiss newspaper Neue Zürcher Zeitung (NZZ) has published an article about the groundbreaking research of NOMIS Distinguished Scientist Tony Wyss-Coray, professor of neurology and neurological sciences at Stanford University. Wyss-Coray’s research has shown that circulatory factors can modulate neurogenesis, neuroimmunity and cognitive function in mice and that blood-derived factors from young mice or humans can rejuvenate the aging mouse brain.

The article (“Der Verjüngungskur auf der Spur”) was published on Dec. 1, 2017 in NZZ.

NOMIS is supporting Wyss-Coray’s continued research into identifying the circulatory factors that influence aging and using those factors to rejuvenate the aging or degenerated brain.

The collaborator: NOMIS researcher Eric Reiman is on a quest to prevent Alzheimer’s disease by sharing big data

“We are living in an
age in which no single person, laboratory or discipline has the resources and skills
to do everything that’s needed on one’s own.”

Eric Reiman, executive director of the Banner Alzheimer’s Institute, is leading the Platform for the Discovery of Alzheimer’s Disease Mechanisms and Treatments project, which will make the genetic data from the brain tissue of 100 donors publicly available. The platform will provide a foundation to develop one of the largest basic and translational neuroscience programs for the fight against Alzheimer’s disease (AD) and other neurodegenerative diseases. Emerging big-data analysis techniques will be used to discover molecular networks involved in the disease and molecular drivers of these networks, including those that could be targeted by new or repurposed treatments.

We spoke with Dr. Reiman about his work and his thoughts on collaboration on the eve of the NOMIS Distinguished Scientist Award 2017 ceremony in Zurich.

NOMIS: You began your career as a psychiatrist and brain imaging researcher. What motivated you to turn your focus to Alzheimer’s disease research?

ER: After moving to Arizona, I had been asked to join the local chapter of the Alzheimer’s Association, and I thought it would be nice to invest in an area of the community that had absolutely nothing to do with my work — I was interested in using brain imaging techniques to investigate regions of the brain that are involved in anxiety, emotion and other normal behaviors, as well as those that conspire to produce anxiety disorders. Even though I would occasionally evaluate patients with memory and thinking problems, it was only as a board member on that chapter that I fully developed an appreciation for the terrible toll that Alzheimer’s disease takes on affected persons and their families. So I decided to explore ways to help make a difference through my research on the brain.

“The opportunity to learn from, assist and work with colleagues from other disciplines and organizations has been one of the joys of my work.”

In 1993, I read a Wall Street Journal article noting the discovery of what turned out to be the major genetic risk factor for developing Alzheimer’s disease. Persons with one copy of the APOE4 gene had a higher risk, and persons with two copies had an even higher risk of developing the disease. I wondered, ‘What if there was a promising way to postpone, reduce, or prevent the clinical onset of Alzheimer’s disease?’ It would take too many healthy volunteers and too many years to evaluate these treatments in prevention trials, waiting for the onset of memory and thinking problems. I then thought, ‘What if we could detect and track the brain imaging changes associated with Alzheimer’s disease in middle-aged persons with two, one or no copies of this gene (i.e., in persons at three levels of genetic risk); thereby detect and track Alzheimer’s long before the onset of memory and thinking problems; and set the stage to use these and other methods to rapidly test prevention therapies and find ones that work, as soon as possible?’ It was kind of a novel idea at the time. But our findings helped kindle interest in the study of what we now call “preclinical Alzheimer’s disease” and ultimately set the stage for Alzheimer’s prevention trials. It would be a dream come true if we could find and support the approval of Alzheimer’s disease prevention therapies by 2025, and that dream motivates me each and every day.

NOMIS: What skills have helped you achieve success in your research? Has collaboration been an influencing factor?

ER: I think I have a knack for identifying good questions and finding new ways to work together with others to have the greatest impact. Why is collaboration so important to everything I do? Perhaps it’s an acute awareness of my own limitations [laughs]. In my opinion, advances in 21st century science and medicine will depend on new models of collaboration and data sharing. We are living in an age in which no single person, laboratory or discipline has the resources and skills to do everything that’s needed on one’s own.

“None of what we have done or hope to do would be possible in the absence of strategically informed collaborations.”

I’m often asked how we could get different organizations to work together so well in the Arizona Alzheimer’s Consortium. The key to our success has been a heightened sense of “scientific desperation.” With newer, smaller and growing programs in Arizona’s universities, research institutes and academic medical centers, we do not have illusions of self-sufficiency. We are motivated to reach out to partners from different disciplines and organizations to address shared goals and respective interests in more effective ways than we can do on our own. We have used state and private funds to conduct collaborative pilot studies, to foster push-pull relationships involving the development and use of new methods, and to find out which collaborations work. We then use the resulting data in publications and grant applications to support long-standing research programs. We have also capitalized on new public-private partnerships in the Alzheimer’s Prevention Initiative.

None of what we have done or hope to do would be possible in the absence of strategically informed collaborations, a track record of productivity in these collaborations and a genuine interest among each of the stakeholders to value their partners and address both their shared and mutual goals.

NOMIS: Collaboration has certainly been a cornerstone of your work. What qualities do you look for in fellow collaborators?

ER: I am always interested in working with interesting people — investigators with outstanding ideas, a track record of productivity, methodological strength and scientific rigor, as well as young investigators who are committed to developing those skills and using them in impactful ways. I look for people with complementary strengths, a collaborative spirit and shared values. And I look for that gleam in the eye during initial discussions about collaborative possibilities. The opportunity to learn from, assist and work with colleagues from other disciplines and organizations has been one of the joys of my work.

NOMIS: The Alzheimer’s platform project will generate a public resource of detailed gene expression data in an effort to galvanize the discovery of Alzheimer’s disease mechanisms, risk factors and treatments. How will this platform change Alzheimer’s disease research?

ER: In previous work, we generated a widely used public resource of neuronal gene expression data in 20 brain donors with and without the clinical and neuropathological features of Alzheimer’s disease. Those data have been used in hundreds of published studies to support the discovery of new Alzheimer’s disease susceptibility genes and possible disease mechanisms.

“We anticipate that this project will provide one of the most valuable and widely used data resources in the scientific fight against Alzheimer’s disease.”

With the advent of new technologies and big-data analysis methods, we can now generate detailed information about genes that are differentially expressed in individual brain cells and their relationship to inherited genes; use these data to explore the molecular networks involved in the development of Alzheimer’s disease; and provide molecular targets at which to aim new treatments. Moreover, we can provide an invaluable public resource of data to the field to further clarify risk factors and disease mechanisms, develop a more diverse portfolio of promising treatments, and do so in ways that might be particularly relevant to this fundamentally human disease.

We anticipate that this project will provide one of the most valuable and widely used data resources in the scientific fight against Alzheimer’s disease and a foundation for future studies. We’re excited about the chance to provide a bridge between these correlational data from people with experimental studies in laboratory models. It will enable us to find better ways to address Alzheimer’s disease than studies in people or laboratory models alone.

NOMIS: How will the platform change the way researchers collaborate?

ER: We are interested in promoting active “push-pull relationships” among researchers who conduct studies in expired brain donors, living people and laboratory models, helping them to capitalize on complementary approaches and converge findings to fulfill their respective and shared goals. We want to embed our big-data specialists in our basic science labs to help foster those collaborations and further clarify disease mechanisms. Once researchers see the added value of these kind of collaborative relationships, they will embrace the approach more fully in their own work. We are also interested in finding ways to share data and biological samples (for example, brain tissue) with researchers around the world, such that they can capitalize on their own expertise, resources and time to advance the scientific effort.

When it comes to the fight against Alzheimer’s disease — and to the advancement of science and medicine more generally — we’re all in this together. ♦

This interview was conducted by Sarah Stoeter and Cosima Crawford on Oct. 18, 2017 at ETH Zurich. Download the unabridged interview.

Eric Reiman is executive director of the Banner Alzheimer’s Institute and chief executive officer for Banner Research. He is also professor of psychiatry at the University of Arizona, university professor of neuroscience at Arizona State University, clinical director of neurogenomics at the Translational Genomics Research Institute (TGen) and director of the Arizona Alzheimer’s Consortium. He is a recipient of the Potamkin Prize for his contributions to Alzheimer’s disease research.