Tag Archives: nih

Medical Technology - AZ Business Magazine January/February 2012

NIH awards BAI, Mayo $8.3 million

The National Institutes of Health (NIH) renewed funding for the Banner Alzheimer’s Institute (BAI) and Mayo Clinic, Phoenix, longitudinal study of the earliest changes associated with the risk of developing Alzheimer’s disease at older ages. The award, an estimated $8.3 million over the next five years, continues NIH’s long-term support of the investigation.

The study, which began two decades ago, has been examining the subtle brain imaging, memory and thinking changes that occur in healthy late-middle-aged and older adults who have inherited from their parents either one, two or no copies of the apolipoprotein E (APOE4) gene, the major genetic risk factor for developing late-onset Alzheimer’s. Each additional copy of the gene significantly increases a person’s chance of developing the disease.

“We are extremely grateful to the NIH and our wonderful research volunteers for their support,” said Dr. Eric M. Reiman, BAI Executive Director and one of the study’s principal investigators. “From the beginning, this study has been driven by our interest in finding treatments to prevent or end Alzheimer’s as quickly as possible, and to provide the information and tools needed to do just that.”

By studying individuals at three levels of genetic risk, researchers have been able to get a sneak peek at the changes associated with the risk of Alzheimer’s. As study participants begin to reach older ages, researchers hope to further clarify the extent to which characteristic brain imaging and other biological changes are associated with subsequent clinical decline. Additionally, researchers hope to further clarify the number of at-risk persons needed to conduct prevention trials, as well as share this valuable resource with other researchers and further develop the methods needed to test the range of promising treatments as quickly as possible.

This longitudinal study began in 1994, soon after researchers discovered the APOE4 gene’s contribution to the risk of developing Alzheimer’s. They have been following approximately 200 healthy volunteers with varying copies of the APOE4 gene, starting between the ages of about 50-65. Every two years, participants are monitored using an extensive battery of brain imaging, memory and thinking tests. A growing number of participants have also been providing cerebrospinal fluid samples. As many of the volunteers reach older ages, a growing number are now at risk for developing mild cognitive impairment (MCI) and dementia. This disease progression will give researchers the opportunity to characterize the extent of change in various biomarker and cognitive measurements. Data will be used to evaluate potential treatments that could combat amyloid plaques, which are strongly associated with Alzheimer’s, as well as help inform the design of future prevention trials.

“Like Dr. Reiman, I am excited about the opportunity we have been given to help advance the study of preclinical Alzheimer’s,” said Dr. Richard J. Caselli, Professor of Neurology at Mayo Clinic in Arizona and the study’s other principal investigator. “We also look forward to the chance to share our data and samples with other researchers to help advance the scientific fight against this terrible disease.”

The study has had a profound impact on Alzheimer’s prevention efforts. It has helped shape the field’s understanding of the progressive brain changes that precede the clinical onset of Alzheimer’s by almost two decades. It has also served as the foundation for the Alzheimer’s Prevention Initiative, an international collaborative formed to accelerate the evaluation of promising but unproven therapies. Data from this longitudinal study has also contributed to the development of the National Institute on Aging and Alzheimer’s Association research criteria for pre-clinical Alzheimer’s. It has also provided key information for the first reconceptualization of Alzheimer’s as a sequence of biological changes that progress over a person’s lifetime.

“By providing insights into the earliest Alzheimer’s-related changes to brain function and structure, this study is contributing to the National Plan to Address Alzheimer’ Disease goal of finding effective interventions by 2025,” said Dr. Neil Buckholtz, of the National Institute on Aging, which leads the NIH research program on Alzheimer’s.

This work also includes researchers from Arizona State University, University of Arizona and the Translational Genomics Research Institute, organizations that are partners in the Arizona Alzheimer’s Consortium. Dr. Eric M. Reiman of Banner Alzheimer’s Institute and Dr. Richard J. Caselli of Mayo Clinic are the two principal investigators.

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.

brain

PCH, Barrow and TGen earn NIH grant

Under a new grant from the National Institutes of Health (NIH), Phoenix Children’s Hospital, Barrow Neurological Institute and the Translational Genomics Research Institute (TGen) are studying the role of extracellular RNA (exRNA) as biomarkers in hemorrhagic brain injuries.

The study is being funded by a $4 million grant that is part of an international effort to determine the roles of exRNA in multiple biological processes.

The Phoenix Children’s group will focus on the evaluation of intraventricular hemorrhage (IVH) in newborns, a form of bleeding in the brain that affects approximately 12,000 premature babies in the U.S. every year. Perinatal IVH is commonly associated with the development of cerebral palsy and hydrocephalous. It’s unclear, however, how hydrocephalous develops and how IVH impacts the potential for developing cerebral palsy.

This study is aimed to identify the modulating effects of exRNA on these processes and if so, to develop a testing mechanism to help clinicians identify children who are at increased risk. The development of a prognostic tool would guide doctors to more effective and less invasive treatments.

Investigators at Barrow Neurological Institute at St. Joseph’s Hospital are evaluating a similar model in adults. They are evaluating the role of exRNA in the development of vasospasm following hemorrhagic stroke.

For a video explanation of exRNA, check out this video.

cancer

TGen identifies key lung cancer enabler

Researchers at the Translational Genomics Research Institute (TGen) have discovered a protein, Mcl-1, that helps enable one of the most common and deadly types of cancer to survive radiation and drug treatments.

Non-small cell lung cancer (NSCLC) makes up about 85 percent of the nearly 160,000 Americans expected to die this year from lung cancer, which by far kills more patients than any other type of cancer; accounting for more than 1 in 4 cancer deaths in the U.S. annually. The 5-year survival rate for advanced NSCLC is less than 10 percent.

In the absence of more effective targeted therapies, most lung cancer patients currently rely on platinum-derived chemotherapeutics, such as cisplatin, or radiation therapy.

Previous TGen studies have shown that excessive activation of a cellular signaling mechanism known as TWEAK-Fn14 is linked to the survival and spread of cancer cells.

In a new laboratory study published in the scientific journal Molecular Cancer Research, TGen investigators found that a protein called Mcl-1 helps enable TWEAK-Fn14, which in turn helps protect NSCLC tumors from being destroyed by radiation and drugs.

“Our study demonstrates that the expression of Mcl-1 is necessary to promote the TWEAK-mediated survival of NSCLC tumor cells,” said Dr. Timothy Whitsett, an Assistant Professor in TGen’s Cancer and Cell Biology Division, and the study’s lead author. “By deactivating Mcl-1, we believe we can give these lung cancer patients a better response to standard therapy.”

Employing a drug called EU-5148, laboratory researchers using lung cancer cell lines found they could block Mcl-1 function and halt the TWEAK-Fn14 cellular signaling mechanism.

“Inhibition of Mcl-1 function enhanced chemo- and radio-sensitivity in NSCLC cells. The depletion of Mcl-1 … was sufficient to abrogate the protective effects conferred on lung tumor cells by TWEAK-Fn14 signaling,” according to the study, Mcl-1 Mediates TWEAK/Fn14-induced Non-small Cell Lung Cancer Survival and Therapeutic Response, published online Jan. 27, and awaiting print publication on April 14.

“This work positions both the TWEAK-Fn14 cellular pathway and the Mcl-1 protein as potential therapeutic interventions,” said Dr. Nhan Tran, an Associate Professor in TGen’s Cancer and Cell Biology Division, and the study’s senior author. “Our evidence shows that, if we can bypass these mechanisms, it will be more difficult for these lung cancer cells to evade therapies.”

The study concludes that additional research of Mcl-1 and TWEAK-Fn14 mechanism is needed, eventually leading to clinical trials and more effective treatments that could reduce lung cancer mortality.

The drug, EU-5148, was provided by Eutropics Pharmaceuticals, based in Cambridge, Mass.

Cancer Treatment Centers of America (Goodyear) also contributed to this study.

The study was funded by the National Institutes of Health (NIH).

alzheimers

NIH grants Banner Alzheimer's Institute $33M

In collaboration with the National Institutes of Health (NIH), Banner Alzheimer’s Institute (BAI) announces a major prevention trial to evaluate a treatment in cognitively healthy older adults at the highest known genetic risk for developing Alzheimer’s disease at older ages. An NIH grant, expected to total $33.2 million, will support this research.

The study is part of the Alzheimer’s Prevention Initiative (API), an international collaboration led by BAI to accelerate the evaluation of promising but unproven prevention therapies. It will test an anti-amyloid treatment in about 650 adults, ages 60-75, who have two copies of the apolipoprotein E (APOE4) gene, the major genetic risk factor for late-onset Alzheimer’s. None of the participants will have impairments in memory or thinking at the time they enter the study.

“Once again, we are extremely grateful to the NIH for the opportunity to help accelerate the evaluation of treatments to prevent the clinical onset of Alzheimer’s and find ones that work as soon as possible,” said Dr. Eric M. Reiman, BAI Executive Director. “This trial will allow us to extend our work to individuals at greatest risk at older ages.”

The randomized, placebo-controlled trial, which will take place at BAI and other U.S. sites, will test the treatment’s ability to stave off the memory and thinking declines associated with Alzheimer’s. It will also assess the treatment’s effects on different brain imaging and cerebrospinal fluid measurements of the disease. The specific compound to be evaluated has not been decided.

The trial will test what is often called the amyloid hypothesis, which suggests that accumulation of the protein amyloid in the brain plays a key role in the disease’s progression.  Major funding from philanthropy and industry will also support the trial, and its leaders expect to provide data and biological samples to the research community after the trial’s conclusion to help in the scientific fight against Alzheimer’s.
Individuals in the study will learn their APOE4 status. To help them prepare for this information, BAI has convened an expert committee to develop a comprehensive genetic testing and disclosure plan and to assess the impact of this disclosure during the trial.
“Under the National Plan to Address Alzheimer’s Disease, our goal is to prevent and effectively treat the disorder by 2025,” said Dr. Neil Buckholtz, of the National Institute on Aging, which leads Alzheimer’s research at the National Institutes of Health.  “We are delighted to support Dr. Reiman, Dr. Tariot and their team in this innovative clinical trial aimed at preventing the onset and progression of this devastating disease.”

The research is intended to complement API’s initial trial, which is primarily focused in Colombia and involves about 300 people from an extended family with a rare genetic mutation that typically triggers Alzheimer’s symptoms around age 45. That work also is focusing on an anti-amyloid therapy and its potential in slowing or blocking the disease while preserving cognitive abilities. The investigation, including a smaller U.S. companion study, dovetails with prevention trials that have been planned or started by other research groups during the past 16 months.
“We are now looking at potential treatments to prevent both the early and late onset forms of the disease,” said Dr. Pierre N. Tariot, BAI Director. “This kind of comprehensive approach could prove the tipping point in our long, arduous effort to find a way to end this devastating disease.”

The new trial will draw participants mainly from the Alzheimer’s Prevention Registry (www.endALZnow.org), an online community of people who are committed to helping in the fight against Alzheimer’s. The Registry provides regular updates on the latest scientific advances, as well as information on overall brain health. To overcome one of the biggest obstacles to clinical research, the Registry supports enrollment in a variety of Alzheimer’s prevention studies within members’ communities.

Alzheimer’s is a debilitating and incurable disease that affects more than 5.2 million Americans, with a new diagnosis every 68 seconds. Without the discovery of successful prevention therapies, the number of U.S. cases is projected to nearly triple by 2050.

alzheimers

NIH grants Banner Alzheimer’s Institute $33M

In collaboration with the National Institutes of Health (NIH), Banner Alzheimer’s Institute (BAI) announces a major prevention trial to evaluate a treatment in cognitively healthy older adults at the highest known genetic risk for developing Alzheimer’s disease at older ages. An NIH grant, expected to total $33.2 million, will support this research.

The study is part of the Alzheimer’s Prevention Initiative (API), an international collaboration led by BAI to accelerate the evaluation of promising but unproven prevention therapies. It will test an anti-amyloid treatment in about 650 adults, ages 60-75, who have two copies of the apolipoprotein E (APOE4) gene, the major genetic risk factor for late-onset Alzheimer’s. None of the participants will have impairments in memory or thinking at the time they enter the study.

“Once again, we are extremely grateful to the NIH for the opportunity to help accelerate the evaluation of treatments to prevent the clinical onset of Alzheimer’s and find ones that work as soon as possible,” said Dr. Eric M. Reiman, BAI Executive Director. “This trial will allow us to extend our work to individuals at greatest risk at older ages.”

The randomized, placebo-controlled trial, which will take place at BAI and other U.S. sites, will test the treatment’s ability to stave off the memory and thinking declines associated with Alzheimer’s. It will also assess the treatment’s effects on different brain imaging and cerebrospinal fluid measurements of the disease. The specific compound to be evaluated has not been decided.

The trial will test what is often called the amyloid hypothesis, which suggests that accumulation of the protein amyloid in the brain plays a key role in the disease’s progression.  Major funding from philanthropy and industry will also support the trial, and its leaders expect to provide data and biological samples to the research community after the trial’s conclusion to help in the scientific fight against Alzheimer’s.
Individuals in the study will learn their APOE4 status. To help them prepare for this information, BAI has convened an expert committee to develop a comprehensive genetic testing and disclosure plan and to assess the impact of this disclosure during the trial.
“Under the National Plan to Address Alzheimer’s Disease, our goal is to prevent and effectively treat the disorder by 2025,” said Dr. Neil Buckholtz, of the National Institute on Aging, which leads Alzheimer’s research at the National Institutes of Health.  “We are delighted to support Dr. Reiman, Dr. Tariot and their team in this innovative clinical trial aimed at preventing the onset and progression of this devastating disease.”

The research is intended to complement API’s initial trial, which is primarily focused in Colombia and involves about 300 people from an extended family with a rare genetic mutation that typically triggers Alzheimer’s symptoms around age 45. That work also is focusing on an anti-amyloid therapy and its potential in slowing or blocking the disease while preserving cognitive abilities. The investigation, including a smaller U.S. companion study, dovetails with prevention trials that have been planned or started by other research groups during the past 16 months.
“We are now looking at potential treatments to prevent both the early and late onset forms of the disease,” said Dr. Pierre N. Tariot, BAI Director. “This kind of comprehensive approach could prove the tipping point in our long, arduous effort to find a way to end this devastating disease.”

The new trial will draw participants mainly from the Alzheimer’s Prevention Registry (www.endALZnow.org), an online community of people who are committed to helping in the fight against Alzheimer’s. The Registry provides regular updates on the latest scientific advances, as well as information on overall brain health. To overcome one of the biggest obstacles to clinical research, the Registry supports enrollment in a variety of Alzheimer’s prevention studies within members’ communities.

Alzheimer’s is a debilitating and incurable disease that affects more than 5.2 million Americans, with a new diagnosis every 68 seconds. Without the discovery of successful prevention therapies, the number of U.S. cases is projected to nearly triple by 2050.