NCTR Conducting Study as Part of FDA Research on Gadolinium-Based Contrast Agents (GBCAs) for Magnetic Resonance Imaging
*Excerpt from MedWatch Safety Alert dated May 22, 2017.
An FDA review to date has not identified adverse health effects from gadolinium retained in the brain after the use of GBCAs for magnetic resonance imaging. All GBCAs may be associated with some gadolinium retention in the brain and other body tissues. However, because FDA identified no evidence to date that gadolinium retention in the brain from any of the GBCAs, including GBCAs associated with higher retention of gadolinium, is harmful, restricting GBCA use is not warranted at this time. FDA will continue to assess the safety of GBCAs and plans to have a public meeting to discuss this issue in the future.
FDA evaluated scientific publications and adverse event reports submitted to FDA. Some human and animal studies looked at GBCA use over periods longer than a year. These publications and reports show that gadolinium is retained in organs, such as the brain, bones, and skin. The publications show that linear GBCAs retain more gadolinium in the brain than macrocyclic GBCAs. However, the review did not identify adverse health effects related to this brain retention.
FDA continues to assess the safety of GBCAs. NCTR is conducting a study on brain retention of GBCAs in rats. Other research is also being conducted about how gadolinium is retained in the body. FDA will update the public when new information becomes available and we plan to have a public meeting to discuss this issue in the future.
Neurodegenerative Markers are Increased in Postmortem BA21 Tissue from African Americans with Alzheimer’s Disease (AD)
NCTR scientists conducted a research study that identified significant differences in AD brain proteins that are related to ethnicity or race. The research community has known that African Americans and Hispanics develop AD at an earlier age and that their symptoms are often more severe, but have not understood why. Although the prevalence of the characteristic plaques and tangles may not exhibit ethnicity-related differences, differences in levels of neurodegenerative proteins have not been described. Because the symptoms of Alzheimer’s are worse in African Americans, understanding the differences in the brain may help explain this.
The NCTR scientists looked at levels of neurodegenerative proteins in the brain tissue of African American men and women, and Caucasian men and women with AD. Some proteins in the brain are associated with AD. For example, levels of the S100B protein are typically increased in the brains of people with AD and brain injuries. Five proteins associated with neurodegenerative diseases were measured (S100B, sRAGE, GDNF, Aβ40, Aβ42 and the Aβ42/Aβ40 ratio). The tissue samples came from the BA21 region (a ridge on the cerebral cortex of the brain) which is involved in language generation and processing and is known to be affected by AD. A multiplex assay was used to determine the levels of these proteins. There were no significant differences between men and women and no significant ethnicity with sex interactions on any protein. Effect size calculations indicated "medium" to "very large" effects. The statistically significant levels of the proteins studied include:
S100B levels were increased 17% in African Americans. S100B is typically elevated in AD cases; however, the increased levels in African Americans here may be indicative of increased severity in specific populations.
Aβ42 levels were increased 121% in African Americans, leading to a 493% increase in the Aβ42/Aβ40 ratio. Increased Aβ42/Aβ40 ratios in this study are compatible with increased disease severity and might indicate increased AD pathogenesis in African Americans.
While many brain proteins are altered in AD patients, these NCTR study results indicate that some of those AD-associated proteins are different between African Americans and Caucasians. The results are compatible with the hypothesis of increased neuroinflammation in African Americans with AD. The next step in this series of studies is to understand what other differences occur in the brains of African Americans and Caucasians with AD, such as 1) different levels of neuroinflammation, 2) differences in chemokines and cytokines in the brain, and 3) genetic differences that might explain the protein level changes. This comprehensive study could potentially lead to targeted pharmacotherapies for specific populations which could better treat AD symptoms and perhaps slow the disease progression. A manuscript describing the study is available online at Journal of Alzheimer’s Disease.
For additional information, please contact Sherry Ferguson, Ph.D., Division of Neurotoxicology, FDA/NCTR. This study was a collaboration with:
Dr. John Panos, *formerly in the Division of Neurotoxicology, FDA/NCTR
Dr. Vijayalakshmi Varma, Division of Systems Biology, FDA/NCTR
Daniel Sloper, Division of Systems Biology, FDA/NCTR.
Nanotechnology Training at NCTR
The NCTR/ORA Nanotechnology Core Facility — located on the Jefferson Laboratories campus in Arkansas — conducted a “Nanotechnology Hands-on Training” course from June 27-29, 2017. In attendance were 12 FDA reviewers and research staff from different FDA product centers and offices. This annual training was sponsored by the FDA Nanotechnology Task Force/Office of Chief Scientist with instructors from FDA’s NCTR, Office of Regulatory Affairs, Center for Drug Evaluation and Research, and Center for Devices and Radiological Health. The lecture topics included:
basic tools and instrumentation used for nanomaterial characterization (Transmission and Scanning Electron Microscopy, Atomic Force Microscopy, Dynamic Light Scattering and Asymmetric, and Centrifugal Flow Field Flow Fractionation)
regulatory considerations for generic and new drug products and devices containing nanomaterial
evaluation of data
nanomaterial and product specific issues to be considered when reviewing submissions.
Save the Date: 2017 Global Summit for Regulatory Science
FDA/NCTR will be co-hosting the 2017 Global Summit for Regulatory Science with the Brazilian Health Regulatory Agency — ANVISA — to be held in Brasilia, BRAZIL on September 18-20, 2017. The Global Summit on Regulatory Science (GSRS) is an international conference for discussion of innovative technologies and partnerships to enhance translation of basic science into regulatory applications within the global context. The conference provides an opportunity for scientists from government, industry, and academic-research communities to objectively assess the utility of emerging technologies for addressing regulatory-research questions and to discuss the best way to translate these technologies into real-world applications. It provides a platform where regulators, policy makers, and bench scientists from various countries can exchange views on how to develop, apply, and implement innovative methodologies into regulatory assessments in their respective countries, as well as harmonizing strategy via global collaboration. To engage the global community to address regulatory-science research and training needs, GSRS will be held in different countries on an annual basis.
The theme for this year’s GSRS is “Emerging Technologies for Drug and Food Safety” and in addition to panel discussions and poster sessions, the agenda will include the following scientific topics:
Global Regulatory Landscape
Emerging Fields and Methodologies
Drug and Food Safety
Towards Acceptance of New Approaches to Safety Assessment: Standards and Reproducibility
Science-Based Regulatory Practice.
There is no registration fee; however, registration is required to attend the conference. For additional information and any updates, visit www.fda.gov/GlobalSummit where you can also find the contact information for the conference coordinator.
ver historia personal en: www.cerasale.com.ar [dado de baja por la Cancillería Argentina por temas políticos, propio de la censura que rige en nuestro medio]//
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