Tag Archives: researchers

alzheimers

Banner Alzheimer’s Institute partners with Novartis

Jessica Langbaum, Ph.D.

Jessica Langbaum, Ph.D.

Researchers from the Banner Alzheimer’s Institute (BAI) today announced a partnership with Novartis in a pioneering medical trial to determine whether two investigational anti-amyloid drugs—an active immunotherapy and an oral medication—can prevent or delay the emergence of symptoms of Alzheimer’s in people at particularly high risk for developing the disease at older ages.

The five-year APOE4 trial will involve more than 1,300 cognitively healthy older adults, ages 60 to 75, at high risk of developing symptoms of Alzheimer’s because they inherited two copies of the apolipoprotein E (APOE4) gene—one from each parent. About 2 percent of the world’s population carries two copies of this gene and one in four people carry one copy of the APOE4 gene, which is strongly linked to late-onset Alzheimer’s.

The trial—subject to regulatory authority approval—will begin in 2015 at approximately 60 sites in Europe and North America, including BAI’s headquarters in Phoenix, Ariz. Participants will receive either the active immunotherapy or the oral medication or a placebo.

The study is partially funded by a $33.2 million grant commitment from the National Institutes of Health (NIH), part of the U.S. Department of Health and Human Services, awarded in 2013, and
more than $15 million in philanthropic and in-kind contributions by Banner Alzheimer’s Foundation. It is part of the Alzheimer’s Prevention Initiative (API), an international collaboration led by BAI to accelerate the evaluation of promising prevention therapies.

Today’s announcement of the partnership with Novartis, a Swiss pharmaceutical company, and the selection of the drugs to be studied, represent a dramatic investment in novel approaches to Alzheimer’s prevention research.

“We hope Novartis’s substantial investment of resources and expertise will lead to a significant breakthrough in Alzheimer’s research,” said Dr. Pierre N. Tariot, study director for BAI, an arm of Banner Health, one of the largest nonprofit healthcare systems in the United States. “We are taking clinical trials to a critical new stage. This approach shifts the research paradigm from trying to reverse disease damage to attacking and preventing its cause, years before symptoms could surface.”

The active immunotherapy is aimed at triggering the body’s immune system to produce antibodies that attack different forms of the amyloid protein, which many researchers have suggested plays a critical role in the development of Alzheimer’s. The oral medication is a BACE (beta-secretase1) inhibitor, designed to prevent the production of different forms of the amyloid protein.

The two drugs, which will be tested separately, are intended to stop the accumulation of amyloid in ways that differ from the anti-amyloid antibody therapies now being tested in API’s Autosomal Dominant Alzheimer’s Disease (ADAD) trial in Colombia, and in two other prevention trials. The drugs are being introduced even before amyloid accumulates in some of the participants’ brains. The trial will increase the chance of finding treatments that will prevent, slow or delay the loss of memory and other cognitive abilities associated with Alzheimer’s.

The new study marks the second major trial associated with API. In 2012, NIH announced the long-term ADAD study of cognitively healthy individuals who are destined to develop Alzheimer’s at an unusually early age because of their genetic history. The $100 million study—funded by NIH, BAI and Genentech, a biotechnology company—is focused on approximately 300 members of an extraordinarily large family from Colombia who share a rare genetic mutation that typically triggers Alzheimer’s symptoms around age 45.

The ADAD study, a partnership of BAI, Genentech and the University of Antioquia in Colombia, is evaluating the amyloid antibody agent crenezumab.

“There are no guarantees that any of these investigational treatments will prevent the clinical onset of Alzheimer’s disease,” said Dr. Eric M. Reiman, one of the study directors for BAI. “But we are grateful for these opportunities to find out.”

The APOE4 and ADAD trials will be critical in determining whether anti-amyloid treatments are likely to show benefit for Alzheimer’s. Both trials include the best-established cognitive and biological measures of the disease, and a strategy that might make it possible to substantially shorten the time needed to conduct future prevention trials. Both trials also include precedent-setting agreements for the sharing of study data and biological samples after the studies conclude.

Volunteers for the APOE4 study will receive either active immunotherapy injections or a BACE inhibitor in pill form or a placebo. Participants will be recruited via multiple venues, including the Alzheimer’s Prevention Registry website created by BAI in 2012. The registry (www.endALZnow.org) currently has more than 37,000 potential volunteers and is aiming to recruit more than 250,000.

The APOE4 study’s new website, which will launch in 2015, will create a platform to explain the study, register potential participants and provide disclosure information and consent forms. Volunteers who meet the study criteria will be asked to mail a sample of their genetic material (such as a cheek swab) to a laboratory. The volunteers will learn the results of that test in the context of possibly enrolling in the trial.

“This web research platform creates a powerful tool for any additional Alzheimer’s research,” said Jessica Langbaum, Ph.D., co-director of the study at BAI. “This infrastructure enables us to create more than just a single drug trial, but rather a template for testing a variety of treatments for many years to come.”

Volunteers who are selected will receive genetic counseling, as will others who are not chosen but who seek more information on their vulnerability. “We are keenly aware of the extreme sensitivity and emotional impact of disclosing genetic information,” Dr. Langbaum said. Volunteers accepted into the trial will already know they are at high risk, while others may learn of a lesser but still increased risk. For both of these groups, BAI will be providing more detailed information and genetic counseling in person, by phone or possibly through video-conferencing or telemedicine.

“We are excited about the chance to partner with Novartis, which has a longstanding commitment to the fight against Alzheimer’s and promising investigational treatments. They will conduct this study in a way that will be helpful to all stakeholders in the field,” said Dr. Tariot.

“We are now coming to believe that attacking Alzheimer’s disease, before clinical signs of memory loss and cognitive impairment become evident, may provide our best chance for effective therapies,” says Dr. Neil Buckholtz, Director of the Division of Neuroscience at the NIA. “These studies will be important in helping to determine if and how that can be done.”

Alzheimer’s is a debilitating and incurable disease that affects as many as 5 million Americans age 65 and older, according to a number of estimates. Without the discovery of successful prevention therapies, the number of U.S. cases is projected to nearly triple by 2050.

cancer

UA Shows Curcumin Effect on Colon Cancer

A team of researchers led by the University of Arizona Steele Children’s Research Center discovered that curcumin—the bioactive molecule derived from the spice turmeric—blocks the protein cortactin in colon cancer.

Cortactin, a protein essential for cell movement, frequently is overexpressed in cancer, thus facilitating cancer cell metastasis to other organs in the body.

Colon cancer is the second leading cause of cancer-related deaths in the United States and the third most common cancer in men and women. When cancer metastasizes to other organs, a patient’s chances of survival are greatly diminished. Thus, finding novel ways to prevent cancer metastasis remains an urgent need.

The National Institutes of Health-funded research recently was published in PLOS One.

The study was led by co-investigators Fayez K. Ghishan, MD, professor and head, UA Department of Pediatrics and director of the UA Steele Children’s Research Center; Pawel Kiela, DVM, PhD, associate professor, UA Department of Pediatrics; and Vijay Radhakrishnan, PhD, assistant scientist, UA Department of Pediatrics. The study was conducted in collaboration with Jessie Martinez, PhD, professor, UA Cancer Center, and Eugene Mash, PhD, professor, Department of Chemistry and Biochemistry.

Turmeric gives curry its yellow color and flavor. It is part of the ginger family and has been used for thousands of years to treat colds, inflammation, arthritis and many other ailments, including cancer.

Curcumin is the active ingredient in turmeric and has been scientifically studied in many types of cancer. It has been shown to have a chemopreventative effect—the ability to reverse, suppress or prevent the development of cancer.

“What’s novel about our research is that our study identified one of the mechanisms by which curcumin can prevent cancer cell metastasis in colon cancer,” said Dr. Ghishan.

The research team discovered that the active part of the cortactin protein, known as Phopsho Tyrosine 421 (pTyr421), is hyper-activated in malignant tumors of the colon.

“We showed that the cortactin protein was hyper-activated due to a process called excessive phosphorylation,” said Dr. Kiela.

Phosphorylation is the addition of a phosphate group to a protein, and is responsible for turning proteins on and off, altering the protein’s function and activity. Too much cortactin, and its activation by phosphorylation, has been linked with cancer aggressiveness.

The researchers treated human colon cancer tumor cells with curcumin. “We discovered that curcumin turns off the active form of cortactin,” explained Dr. Radhakrishnan, who led the experiments in the lab. “Thus, when cortactin is turned off, cancer cells lose the ability to move and can’t metastasize to other parts of the body.”

More specifically, curcumin “turned-off” cortactin by interacting with, and activating, an enzyme known as PTPN1. This enzyme acts as a phosphatase to remove phosphate groups from cortactin—a process known as “dephosphorylation.”

“This effect, essentially known as ‘dephosphorylating cortactin’ correlated with reduced ability of colon cancer cells to migrate,” said Dr. Kiela. “This suggests that curcumin reduces cancer cells’ ability to migrate, meaning the cancer can’t metastasize.”

“By identifying the mechanism of action—that curcumin activates the enzyme PTPN1, which then ‘turns off’ the active component of cortactin pTyr421, we believe that chemopreventative drugs can be developed to target cortactin in cancer cells to prevent the cancer from metastasizing,” said. Dr. Radhakrishnan.

“Treatments aimed at the suppression of cancer metastasis remain an urgent therapeutic need,” said Dr. Ghishan. “Our findings have laid the foundation for future research to develop treatments using curcumin to prevent cancer’s deadly spread to other organs.”

stem.cell

TGen researchers uncover root of myeloma relapse

Researchers have discovered why multiple myeloma, a difficult to cure cancer of the bone marrow, frequently recurs after an initially effective treatment that can keep the disease at bay for up to several years.

Working in collaboration with colleagues at Princess Margaret Hospital in Toronto, researchers from Mayo Clinic in Arizona and the Translational Genomics Research Institute (TGen) in Phoenix were part of the team that conducted the study published in the Sept. 9 issue of Cancer Cell.

The research team initially analyzed 7,500 genes in multiple myeloma cells to identify genes which when suppressed made cancer cells resistant to a common class of drugs called proteasome inhibitors such as bortezomib or carfilzomib. Then, the team studied bone marrow biopsies from patients to further understand their results. The process identified two genes (IRE1 and XBP1) that control response to the proteasome inhibitor and the mechanism underlying the drug resistance that is the barrier to cure.

The findings showed recurrence was due to an intrinsic resistance found in immature tumor progenitor (mother) cells is the root cause of the disease and also spawns relapse. The research demonstrates that although the visible cancer cells that make up most of the tumor are sensitive to the proteasome inhibitor drug, the underlying progenitor cells are untouched by this therapy. These progenitor cells then proliferate and mature to reboot the disease process, even in patients who appeared to be in complete remission.

“Our findings reveal a way forward toward a cure for multiple myeloma, which involves targeting both the progenitor cells and the plasma cells at the same time,” says Rodger Tiedemann, M.D., a hematologist specializing in multiple myeloma and lymphoma at Princess Margaret. “Now that we know that progenitor cells persist and lead to relapse after treatment, we can move quickly into clinical trials, measure this residual disease in patients, and attempt to target it with new drugs or with drugs that may already exist.”

“Some myeloma cells are too immature to be caught by the drugs and thus hide underground only to reemerge later,” says Keith Stewart, M.B., Ch.B., Dean for Research at Mayo Clinic in Arizona and contributor to the study. “This study has wide implications in the search for a cure of this common blood cancer as this ‘progenitor cell’ will have to be targeted.”

Jonathan Keats, Ph.D., head of TGen’s Multiple Myeloma Research Laboratory, said: “This study, which leverages data generated at TGen as part of the Multiple Myeloma Genomics Initiative, shows how mutations acquired by multiple myeloma tumors can make a tumor resistant to specific therapies and highlights the importance of TGen’s precision medicine approaches.”

Dr. Tiedemann says: “If you think of multiple myeloma as a weed, then proteasome inhibitors are like a goat that eats the mature foliage above ground, producing a remission, but doesn’t eat the roots, so that one day the weed returns.”

The study — Xbp1s-Negative Tumor B Cells and Pre-Plasmablasts Mediate Therapeutic Proteasome Inhibitor Resistance in Multiple Myeloma — was funded by the National Cancer Institute, Multiple Myeloma Research Foundation, Leukemla and Lymphoma Society and Canadian Cancer Society, the Arthur Macaulay Cushing Estate and The Princess Margaret Cancer Foundation.

Dr. Tiedemann is the Molly and David Bloom Chair in Multiple Myeloma Research, at the University of Toronto, Dr. Stewart is the Anna Maria and Vasek Pollack Professor of Cancer Research at Mayo Clinic. Dr. Keats is an Assistant Professor in TGen’s Integrated Cancer Genomics Division.

native.american

UA Part of $6M research of American Indian Health

Public health researchers at the University of Arizona, along with researchers at two other higher education institutions in the state, have earned a $6 million grant to investigate health issues in American Indian communities.

The National Institutes of Health’s National Institute on Minority Health and Health Disparities awarded the five-year grant to a statewide team of researchers from the UA, Northern Arizona University and Diné College to establish the Center for American Indian Resilience, also known as CAIR.

The collaborative team will study why some American Indian communities facing high rates of chronic disease and poverty seem to thrive despite adversity.

“The basic practice of public health is about understanding ways to support healthy behaviors, and we know programs that are culturally relevant are more effective,” said Nicolette Teufel-Shone, professor of health promotion sciences at the UA’s Mel and Enid Zuckerman College of Public Health.

“We will take a look at existing health behaviors and programs that target the prevention of chronic diseases, such as obesity, diabetes and heart disease, to determine what is working and why,” Teufel-Shone said.

Teufel-Shone and Priscilla Sanderson, assistant professor of health sciences and applied indigenous studies at NAU, have been named CAIR’s co-directors. Diné College faculty on the project are Mark Bauer and Donald Robinson, both of the department of science education.
The UA public health college received $2 million of the CAIR grant, which includes collaborations with tribal communities and research projects.

“CAIR research will deepen our scientific knowledge of existing positive health outcomes in tribal communities, and then we will translate this knowledge to practice through public health education and policy,” said Sanderson, a member of the Navajo Nation.

Also under the grant, the UA public health college will collaborate with NAU and Diné College to support Diné College’s ongoing summer program to teach undergraduate students to consider and incorporate community strengths in their work as emerging public health professionals. The program combines classroom learning with hands-on experience through an internship in tribal communities.

The research project, directed by the UA, also involves a partnership with the Tucson Indian Center to interview elders about their concept of resilience and their perceptions of key factors that contribute to success in life.

Through this initiative, members of the Southwestern American Indian community will record video diaries to share their experiences of well-being.

“The goal of the video diaries project is to use existing information about which factors contribute to Native American resilience and spread this knowledge to other Native American communities,” Teufel-Shone said. “This way, researchers can learn lessons of how resilience is already effective in these communities, share experiences and allow community members to create new paths based on other people’s stories.”

Other UA College of Public Health participants include John Ehiri, director and professor; Division of Health Promotion Sciences; Agnes Attakai, director, Health Disparities Outreach and Prevention Education; Kerstin Reinschmidt, assistant professor, Health Promotion Sciences; and Rebecca Drummond, program director for Family Wellness.

NAU faculty and staff contributing to CAIR include Olivia Trujillo, professor of applied indigenous studies; Robert Trotter, Regents’ professor and chair of anthropology; Chad Hamill, assistant professor of music; Roger Bounds, associate professor and chair of health sciences; Lisa Hardy, assistant professor of anthropology; R. Cruz Begay, professor of health sciences; and Kelly Laurila, coordinator in anthropology. Paul Dutton, director of NAU’s Interdisciplinary Health Policy Institute, will facilitate the executive advisory board.

Diné College faculty on the project are Mark Bauer, PhD and Donald Robinson, PhD of the Department of Science Education.

home.prices

Phoenix’s median home price continues to rise

A new report by real state researchers at Arizona State University says the median home price in metro Phoenix during October increased by 34 percent when compared to the same period a year before.

The report by the university’s W.P. Carey School of Business says the median home price stood at $157,000 in October.

The median home price for October 2011 was $116,000.

The researchers also said the supply of homes and condos in metro Phoenix increased 31 percent over the past three months.