Developments to Watch: New frontier in Alzheimer’s disease

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Medscape, a physician-oriented website run by WebMD, visited Sanford-Burnham’s La Jolla campus this summer to record interviews with researchers from both Orlando and San Diego for a new online video program called Developments to Watch. The talk show-like discussions are hosted by Dr. Evan Snyder, who directs the Stem Cells and Regenerative Biology Program at Sanford-Burnham. The first episode, A New Frontier in Alzheimer’s Disease, is now available. In the video, Dr. Snyder speaks with Dr. Stuart Lipton, director of the Del E. Web Neuroscience, Aging and Stem Cell Research Center, about his work on Alzheimer’s disease. They discuss what new findings—and potential treatments—are on the horizon and how they might impact patients.

A user name and password are required to access Medscape, but the site and content are free. New installments will be added monthly.

Watch the video, then come back here to let us know what you think!

For more about our research on Alzheimer’s disease, check out these blog posts:
Getting to the root of Alzheimer’s disease
Diagnosing Alzheimer’s Earlier
New Partnership Targets Brain Conditions
Safely Treating Alzheimer’s Disease
Saying NO to Alzheimer’s and Parkinson’s Diseases

Crunching the Proteome

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Every day we gain a better understanding of how cells work. In the past 20 years, new tools to examine gene expression and function have illuminated many different mechanisms that guide all aspects of cellular behavior. However, to fully understand normal cellular functions and how they malfunction in disease, we need more in-depth information about the many proteins our genes produce. Which proteins are being produced? How are they modified? What is each protein’s ultimate function and how do they interact on a system-wide level? New technologies in the proteomics facility at Sanford-Burnham are providing reams of data that could help answer these and many other questions.In a room full of advanced technology, the Thermo LTQ-Orbitrap Velos mass spectrometer system stands apart. The system has been part of the proteomics toolbox for about a year and has proven its value identifying proteins several times over. Dr. Laurence Brill, director of Advanced Proteomics in Sanford-Burnham’s Proteomics Facility, notes that the Velos system is 10 times more sensitive and three times faster than previous machines, but there’s a lot more to the core’s success than the excellent equipment. “We use very stringently applied analytical methods that take years to develop and refine,” says Dr. Brill. “We are thinking very carefully about the goals and biology of each assay and making them reproducible from run to run.”

Support Spinal Cord Injury Research

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by Paula Baldin

How can you help support spinal cord injury research?
Write a letter of support
for renewal of the Roman Reed Spinal Cord Injury Research Act.
Let your Representative know
that you support federal funding for stem cell research.

During a college football game in 1994, young NFL hopeful Roman Reed suffered a debilitating spinal cord injury that left him paralyzed. As a result of this tragedy, Roman and his father, Don C. Reed, created the Roman Reed Foundation to increase awareness of paralysis. The foundation supports studies of both the causes and potential therapies for neurological disorders, especially those aimed at mitigating spinal cord injury through regenerative medicine. The Reeds lobby tirelessly to promote and fund research in this field.

In 2000, the foundation’s work led to California’s Roman Reed Spinal Cord Injury Research Act, which directed $14.6 million in state funds towards spinal cord injury research. Over the past decade, these funds have grown to $63.8 million through donations and other sources, including the National Institutes of Health (NIH).

The Roman Reed Act is now up for renewal and needs your support.

Bring It! For Stem Cell Research

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Stem cell therapy holds promise for many different areas of medicine. But, as Dr. Evan Y. Snyder, director of Sanford-Burnham’s program in stem cells and regenerative biology, told the rapt Bring It!audience on April 21, regeneration of damaged spinal cord tissue is one of the most exciting stem cell applications. For many of those in attendance, the hope for a spinal cord injury treatment holds a distinctly personal significance – they, or someone they love, have been impacted by such an injury.Bring It! is a game show-themed fundraising experience now in its third year in San Diego. This year, Sanford-Burnham again partnered with HeadNorth, an organization that supports spinal cord injury patients. Life Technologies, leading supplier of stem cell research products to labs around the world, was the presenting sponsor.

But the Bring It! audience didn’t focus on tragedy. Their passion for stem cell research brought them there to play games and raise money. The fundraiser’s theme, “Rock on for Stem Cell Research,” gave participants the chance to live out their rock star fantasies, while helping stem cell treatments become a reality.

Tracking stem cells by MRI

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Neonatal stroke or related brain injuries can occur when a newborn baby’s blood supply is restricted, often leading to cerebral palsy, epilepsy or mental retardation. Over the past decade, researchers have been using animal models to experiment with neural stem cells to replace or protect the damaged tissue in this type of surprisingly common brain injury. Stem cells hold great therapeutic promise because they can proliferate in a dish (making many cells for transplantation purposes) and then differentiate on command, specializing into a specific cell type like neurons in the brain or even glial cells, which support and protect neurons. Stem cells are also pathotropic, meaning that they are drawn to, or home in on, pathological locations in the brain, including those that can occur from injury (like stroke) or degeneration (such as occurs in Alzheimer’s disease).

But there are risks to stem cell therapy. One worry is that cells will continue proliferating after transplantation, leading to tumor formation. Scientists also need to make sure the stem cells migrate directly to the locations in need of repair or protection and not to unintended locations. These are tough problems to overcome, though, because it’s difficult to track a stem cell’s behavior once it’s inside a host.

“The ability to monitor neural stem cells for a long time is particularly important for newborns, where implantation could cause unanticipated effects in the developing brain long into the future,” says Dr. Evan Y. Snyder, director of Sanford-Burnham’s Stem Cells and Regenerative Biology Program. Dr. Snyder was also the first to demonstrate pathotropism of solid-organ stem cells, as well as the first to demonstrate the use of stem cells to treat stroke, particularly neonatal stroke.

On the Cutting Edge

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On April 12, Dr. Evan Snyder, who directs the Stem Cells and Regenerative Biology program at Sanford-Burnham, was interviewed by Shally Zomorodi of Fox 5 News about recent advances in stem cell research. Dr. Snyder singled out four different areas where researchers are making great progress: diseases in a dish; using stem cells to protect other cells; recreating organs for transplant and using stem cells to treat diseased tissues or cancers (particularly in the brain) with targeted gene therapy. Dr. Snyder noted that all these approaches are fairly advanced.

A word of caution on mesenchymal stem cells

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Stem cells of many varieties hold a lot of promise for regenerative medicine. Their ability to continually self-replicate (produce more stem cells) and differentiate (specialize) into any number of cell types make them an enticing replacement for diseased or damaged tissue or as delivery vehicles for therapeutic molecules.The problem is that we still don’t know enough about many of the existing stem cell types to predict exactly how they will behave when transplanted into a patient. Each of the different types of stem cells has its unique repertoire of behaviors and its own benefits and drawbacks. In an editorial appearing online March 25 in the journal Experimental Neurology, Dr. Evan Y. Snyder hammers home the possible dangers of one very popular and oft-used type of stem cell. He highlights a paper appearing in the same issue of that journal, in which researchers from the Aristotle University of Thessaloniki in Greece and the Medical University of Vienna show that brain tumors develop when a mouse model of multiple sclerosis (MS) is transplanted with mesenchymal stem cells (MSCs) derived from bone marrow.

Stem cells reach the crest

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The neural crest is a versatile population of stem cells found in a developing embryo. In humans, neural crest arises during the third to fourth weeks of pregnancy, and then the cells specialize into a diverse set of cells, including certain types of nerves, skin, bone and muscle. Scientists have long appreciated this crucial event in development – when it goes wrong, a number of skeletal and nervous system disorders can result. But they haven’t really been able to study it properly in the laboratory. That’s because of the transient nature of the neural crest – it typically only exists for about two weeks in humans (with few exceptions). After that, the cells have migrated away and differentiated into other tissue types. Dr. Alexey Terskikh (along with Dr. Marianne Bronner-Fraser at the California Institute of Technology, Sanford-Burnham’s Dr. Evan Y. Snyder, postdoctoral researchers Dr. Carol Curchoe and Dr. Jochen Maurer and others) recently discovered a way to overcome this problem. In a study published recently in the journal PLoS ONE, they developed a new protocol for generating early migratory neural crest cells from human stem cells.

“This new system allows us to dissect what happens during human development – something that is not accessible in any other way,” says Dr. Terskikh, associate professor in Sanford-Burnham’s Development and Aging Program.

A new stem cell enters the mix

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Stem cells have the unique ability to self-renew (make more stem cells) and differentiate (specialize into a number of different cell types). There are three main types of stem cells already on the scene: embryonic stem cells, adult stem cells and induced pluripotent stem (iPS) cells. iPS cells are engineered by reprogramming fully differentiated adult cells, often skin cells, back to a primitive state. Like their embryonic cousins, iPS cells can form all cell types. Researchers are currently working to harness the flexibility of stem cells to replace damaged tissue and treat conditions like diabetes and heart disease.

The iPS cell approach to regenerative medicine is tantalizing because these cells could be derived from a patient’s own cells and are therefore less likely to face immune rejection. In the past few weeks, however, a slew of papers have indicated that the therapeutic potential of iPS cells might be limited by reprogramming errors and genomic instability. Given these problems, researchers from Sanford-Burnham, Chung-Ang University in Korea, University of British Columbia, Harvard Medical School and elsewhere wondered if there might be a better way to regenerate lost tissue to treat conditions like heart disease and stroke. Writing March 4 in the Proceedings of the National Academy of Sciences, they outline a method to obtain a new kind of stem cell they call induced conditional self-renewing progenitor (ICSP) cells.

How long do stem cells live?

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Have you or a family member donated bone marrow or received a transplant? We’d love to hear what this type of research means to you. Please drop us a line in the comments below.

When patients receive a bone marrow transplant, they are getting a new population of hematopoietic stem cells. Fresh stem cells are needed when a patient is low on red blood cells, as in anemia, or white blood cells, which can be caused by cancer or even cancer treatments such as irradiation or chemotherapy. The problem is that a bone marrow transplant might not succeed because the transplanted stem cells don’t live long enough or because they proliferate too well, leading to leukemia.

To help determine how long a bone marrow (stem cell) graft will last, researchers have developed a mathematical model that predicts how long a stem cell will live and tested those predictions in a mouse model. The study, led by Dr. Christa Muller-Sieburg, was published online February 28 in the journal Proceedings of the National Academy of Sciences.

“It has long been assumed that stem cells are immortal – they continue to self-renew, thus generating more stem cells that collectively can outlast an individual’s life,” says Dr. Muller-Sieburg, professor in Sanford-Burnham’s Stem Cells and Regenerative Biology Program. “But now we have found that each stem cell is pre-programmed to self-renew only for a set amount of time that, in mice, ranges from a few months to several years. So we created a computer program that predicts that lifespan.”