Consortium for Brain Fatty Acids (CFBFA)

Founding Scientific Directors
Nicolas G. Bazan, M.D., Ph.D.	Louisiana State University Medical Center and Neuroscience Center of Excellence, New Orleans, LA, U.S.A.
Lester R. Drewes, Ph.D.	University of Minnesota School of Medicine, Duluth, MN, U.S.A.
James A. Hamilton, Ph.D.	Boston University School of Medicine, Boston, MA, U.S.A.
Hugo W. Moser, M.D.	Kennedy Krieger Institute and Johns Hopkins University School of Medicine, Baltimore, MD, U.S.A.
Arthur A. Spector, M.D.	University of Iowa College of Medicine, Iowa City, IA, U.S.A.
Managing Director
Robert Katz, Ph.D.	Omega-3 Research Institute, Inc., Bethesda, MD, U.S.A.

What is the Consortium?

The Consortium for Brain Fatty Acids (CFBFA) is a centrally managed, administered and coordinated collaborative association of research groups that conduct focused research on the role of brain fatty acids in health and disease. The Scientific Director of each group and the associated analytical laboratory bring a wealth of expertise and experience to address issues of client interest.

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Objectives of the Consortium

To facilitate progress in understanding the functions of fatty acids and their derivatives in the healthy and diseased central nervous system (CNS) by providing:
- basic or clinical research and development services
- interdisciplinary collaborations
- analytical, clinical and diagnostic "gold standard" laboratory services
To elucidate the preventative and therapeutic potential of polyunsaturated (essential) fatty acids and their derivatives in disorders of the CNS, such as bipolar mood disorder, unipolar depression, schizophrenia, brain developmental and inherited metabolic disorders, inflammatory disease, stroke, neurodegenerative diseases of aging, brain cancers, retinal degeneration, etc.

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Clientele

Industry

Government agencies

Clinical researchers

Medical practitioners

Academic researchers and their teams

Foundations

Research centers or institutes

Consortia

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Available Services

Research and Development Services and Collaborations:

Basic and applied fatty acid research for the development of new approaches, elucidation of mechanisms, techniques, syntheses, and methods. (See "Scientific Areas").
Design, planning and implementation of clinical studies or trials for preventative and therapeutic interventions with fatty acids and their derivatives.
Collaborative research and training opportunities for predoctoral, doctoral, postdoctoral and experienced researchers in the brain fatty acid areas.

For a description of Scientific Directors, members of the Consortium, who are providers of research and development services, click here.

Parties interested in research and development services should complete the attached form and click on the "Submit" button. The completed form will be electronically transmitted to Robert Katz, Director, CFBFA, O3RI.

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Analytical and Diagnostic Services Provided:

Quantitation of plasma and erythrocyte fatty acid concentrations and determination of phospholipid, plasmalogen, glyceride and lipoprotein levels for clinical research and diagnostic purposes.
Development and/or validation of new methods and assays for localization and quantitation of fatty acids and their derivatives in the CNS.
Qualitative and quantitative analytical assessment of nutritional oils utilized for supplementation of CNS fatty acids.

For a description of the laboratory's capabilities click here.

Parties interested in analytical and diagnostic services should complete the attached form and click on the "Submit" button. The completed form will be electronically transmitted to Robert Katz, Director, CFBFA, O3RI and Ann Moser, Manager, Peroxisomal Disorders Laboratory.

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Special Projects in Support of Small Business Research:

Assistance to small business enterprises, that qualify for federal research and development support, in the preparation of their grant applications.
Development of collaborative project with the Scientific Directors for small business technology transfer research grants.

Parties interested in special projects in support of small business research should complete the attached form and click on the "Submit" button. The completed form will be electronically transmitted to Robert Katz, Director, CFBFA, O3RI.

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Scientific Areas:

Fatty acids (FAs), stress-sensitive protein kinases, transcription factors, pro-inflammatory gene-promoters and cell survival genes in signal transduction mechanisms in CNS membranes
Quantitation of dietary FA uptake through the blood-brain barrier (BBB)
Formation and function of tight junctions in the BBB during brain development
Construction of BBB expression databases in embryonic, neonatal and developing brain (in rats and humans), the healthy adult brain and in brain cancers
Intercellular shuttling, intermediary metabolism and catabolism of fatty acids in the developing and mature CNS
Quantitation, imaging and metabolism of essential FAs and phospholipids in animal and human brain
Assessment and quantitation of remodeling of brain fatty acids in membrane lipids
Essential FAs in glial and neuronal membranes and their role in brain development, nutritional deficiencies, bipolar disorder, unipolar depression, schizophrenia, neurodegenerative diseases, inherited metabolic diseases, disorders of oxidative stress, stroke, inflammatory diseases and brain cancers
Assessment of changes in steady states of brain fatty acids in response to centrally acting drugs and pathological changes in bipolar and other disorders
Essential fatty acid delivery to the retina and neurons
Clinical studies of nutritional supplementation of omega-3 FAs or omega-6 FAs
Synthetic and biosynthetic approaches to fatty acids and their derivatives
Development of new therapeutic strategies
Development of nanotechnology-based neuronal signal transducing systems
Analytical quantitation of FAs and their derivatives in animal and human tissue samples
Analytical evaluation of oils to be used in CNS research and clinical trials

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Instrumental Resources and Research Materials Available

Advanced Molecular Analysis Center (AMAC) for Cerebrovascular Research

Microarray analysis for cDNA microarray hybridization, scanning and analysis
DNA sequencing facilities for clones, PCR products, and vector inserts
Quantitative mRNA analysis of target transcripts by PCR (real-time fluorescence)
Immunocytochemistry of protein expression in neural tissue
Immunoelectron microscopy for cellular and subcellular localization of antigens by electron microscopy using immunogold labeled secondary antibodies
Production of affinity-purified polyclonal anti-peptide antibodies raised in chickens

A Nuclear Magnetic Resonance (NMR), Electron Paramagnetic Resonance (EPR) and Fluorescence Spectroscopy Laboratory Containing the Following:

A Bruker NMR spectrometer system (with a wide-bore 500 MHz magnet, with six probes and magic angle spinning and imaging accessories) that provides the following capabilities: (i) high resolution solution-state determination of protein structure, (ii) high resolution in vivo studies with small animals, (iii) magic angle spinning analysis of liquid-crystalline and crystalline phases in membranes and biological tissues, and (iv) imaging of tissue and small animals.
A Bruker EPR spectrometer with a 10-inch magnet, variable temperature control, and microwave bridges for analysis of chemical and biological samples.
A new Spex FluoroMax-2 highly sensitive spectrofluorimeter (with novel Grams/386 analysis software) that permits simultaneous monitoring of the changes in fluorescence of two fluorescent probes in cell suspensions or model membranes.
A High Tech stopped-flow accessory that can measure rapid kinetics (time resolution of msec).
A dual wavelength excitation light source imaging system that allows measurements of pH in single cells.
An emission light detection system comprised of an intensified video camera and computerized data storage.

Signal Transduction Monitoring Laboratory:

Laser confocal microscope for measuring calcium signaling.
Imaging technology for cell signaling transduction.
Several capillary gas chromatographs for detection of very low level release of fatty acids from synapses
Model systems for the study of omega-3 FAs in retina.

Other:

Through Associated Scientific Collaborators the Consortium has access to magnetic resonance imaging and positron emission tomography for large animals and humans.

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Consortium Management

Robert Katz, Ph.D., Director, Consortium for Brain Fatty Acids, (CFBFA), and President, Omega-3 Research Institute, Inc., (O3RI), 3 Bethesda Metro Center, #700, Bethesda, Maryland 20814.

Expertise: Dr. Katz managed, administered and coordinated large scale, nationwide biomedical research and development programs for about 15 years. (As a former extramural grants program director at the National Institutes of Health). In 1993 he founded a biotech company where he co-designed and patented long chain omega-3 PUFA derivatives for passage through the BBB and for specific transport and delivery of large, biologically active molecules to neurons astrocytes. In 1998 he founded O3RI where he co-organized an international workshop on Brain Uptake and Utilization of Fatty Acids: Application to Peroxisomal Biogenesis Diseases (for workshop summary and recommendations stemming from the workshop please visit the O3RI web site at URL: http://www.omega3ri.org). He is also a co-organizer of an upcoming international workshop on Omega-3 Fatty Acids, Diabetes and Cardiovascular Risk (visit the above URL for workshop agenda).

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Corporate Sustaining Associates

Corporations and Foundations are encouraged to become Sustaining Associates of the Consortium. Becoming a Sustaining Associate entitles the Corporation or Foundation to undertake research, development or clinical testing programs within the framework of the Consortium. The annual fee for becoming a Sustaining Associate is $5,000/year. To express interest in becoming a sustaining associate, please complete the attached form.

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Inquiries

If you are interested in any of the services offered (Analytical or Diagnostic; or Research or Development; or Special Projects in Support of Small Business Research) or you wish to receive information on how to become an Associate Scientific Collaborator, please complete and forward the corresponding attached form. Alternatively, you can contact Robert Katz, Ph.D., Director, CFBFA by telephone (301-961-1918), by fax (301-417-9087) or e-mail at omega3ri@aol.com.

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Analytical, Clinical and Diagnostic Laboratory for Fatty Acids and Derivatives

Ann Moser, Manager, Peroxisomal Disorders Laboratory, Kennedy Krieger Institute, Baltimore, Maryland, U.S.A.

Expertise: Examples of research samples analyzed include: peroxisomal disorders (X-linked adrenoleukodystrophy, Zellweger syndrome, etc.) mitochondrial fatty acid oxidation disorders (MCAD, LCHADD, CPT2 deficiency) and other disorders (PKU, ataxia telangiectasia, retinitis pigmentosa, Down syndrome, Alzheimer's disease and autism). The development of new techniques and methods will be undertaken as needed. During the period July 1, 1998 to June 30, 1999 a total of 2250 diagnostic and 1120 research samples were analyzed for total lipid profiles by laboratory staff.

H. Umesha Shetty, Ph.D., President, Celkem, Inc., Silver Spring, Maryland.

Expertise: Celkem is an analytical laboratory, in formation, for the analysis of phospholipids and their structural components such as diacylglycerides, fatty acids and headgroups (e.g., myo-inositol). Dr. Shetty is an expert in developing new and appropriate methodologies for quantitation of these molecules in biological samples. He is also expert in analysis of oils used as nutritional supplements.

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Capabilities of the Clinical and Diagnostic Laboratory

Assessment of total serum and red blood cell (RBC) membrane lipid fatty acids from C8:0 to C26:0, (including saturates, monounsaturates, polyunsaturates and several trans fatty acids). As many as 67 individual fatty acids can be included in the provided analysis. Results are reported on special forms and as Excel spreadsheets.
Quantitation of plasmalogens in RBC as their acid derivatives. (In addition to human plasma and red blood cell samples, laboratory staff have measured total lipid fatty acids, including the essential fatty acids in tissue from knockout mouse models for X-linked adrenoleukodystrophy, Zellweger syndrome and the 70 kD peroxisomal membrane protein.)
Quantitation of plasma phospholipids and their polyunsaturated fatty acid content.
Phosphatidylethanolamine separation from total serum lipid extract and its quantitation.
Analyzes of circulating plasma or adipose tissue triglycerides in fasting individuals for their weight % of linoleate to linolenate content expressed as percent of daily energy intake.
Extraction of human and animal post-mortem brain white and gray matter to measure the total lipid profile of brain lipids in order to identify abnormalities that might explain the disorders of myelin formation and breakdown.

The laboratory is fully equipped with four Hewlett Packard capillary gas chromatographs, each with dual flame ionization detectors, dual injectors and central computer. Another gas chromatograph is in the process of being installed. Two benchtop H.P. GC/MS are available for confirming fatty acid identity. One H.P. 1090 series II HPLC with a diode array detector and programmable fraction collector, TLC equipment, four ultra-cold freezers, two liquid nitrogen freezer, Beckman scintillation counters and three different ultracentrifuges, one microfuge, etc. The laboratory has vast experience with preservation and shipment of samples and can advise clients on appropriate sample preparation. The laboratory is fully licensed by the State of Maryland, certified by the JCAHO and by CLIA.

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Scientific Directors for Research and Development

Nicolas G. Bazan, M.D., Ph.D., Louisiana State University Medical Center and Neuroscience Center of Excellence (LSU), New Orleans, LA

Expertise: Dr. Bazan's expertise encompasses elucidation of the physiological roles of omega-3 essential fatty acids and related bioactive molecules in neuronal cell signal transduction. Stress-sensitive protein kinases, transcription factors, proinflammatory gene promoters, cell survival genes and their participation in molecular neurobiological processes in health and disease are also an integral part of Dr. Bazan's expertise. Other areas of focus include brain and retina cell cultures, and the supply of omega-3 fatty acids to photoreceptors and synapses.

Lester R. Drewes, Ph.D., University of Minnesota School of Medicine, Duluth, MN

Expertise: Dr. Drewes is actively studying the structure of the cerebrovascular endothelium as well as metabolic and transport processes involved in the crossing of the BBB and the understanding of structure-function relationships in cerebral capillary endothelium. Dr. Drewes is assembling a team to undertake the construction of BBB expression databases.

James A. Hamilton, Ph.D., Boston University School of Medicine, Boston, MA

Expertise: Dr. Hamilton's laboratory has pioneered new approaches to monitoring the transmembrane movement of fatty acids and has shown that diffusion is an effective mechanism both for model membranes and cell membranes. Dr. Hamilton will provide a link between the uptake of fatty acids by cell membranes in general and brain cell membranes. His work covers fatty acid transport and metabolism with strong emphasis on biophysical properties and interactions of fatty acids with various membranes by 13-C NMR spectroscopy and fluorescence spectroscopy.

Hugo W. Moser, M.D., Kennedy Krieger Institute and Johns Hopkins University School of Medicine, Baltimore, MD

Expertise: A major aspect of Dr. Moser's expertise is the design and implementation of major therapeutic clinical trials for adrenoleukodystrophy (ALD) and peroxisomal biogenesis disorders (PBDs), both due to accumulations of very long chain saturated fatty acids in the brain. Other researchers at Kennedy Krieger are involved with saturated fatty acid biochemistry and molecular biology, with brain cancer cell biology and tumor angiogenesis.

Arthur A. Spector, M.D., University of Iowa College of Medicine, Iowa City, IA

Expertise: Dr. Spector is studying fatty acid metabolism and transport, including eicosanoids and lipoproteins in cardiovascular disease and the CNS by cell culture and by direct analytical techniques. In collaboration with other researchers at the University of Iowa Dr. Spector is involved in intermediary metabolism of omega-3 PUFA in astrocytes and the elucidation of their potential therapeutic role in brain cancer, e.g., gliomas.

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Background:

The Consortium for Brain Fatty Acids (CFBFA) is an outcome of the International Workshop on �Brain Uptake and Utilization of Fatty Acids: Application to Peroxisomal Biogenesis Diseases,� March 2-4, 2000, Holiday Inn Bethesda, Bethesda, Maryland. The workshop was held under the auspices of the Kennedy Krieger Research Institute, Baltimore, Maryland; the Omega-3 Research Institute, Inc., Bethesda, Maryland; and the Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland and was supported by a grant from the National Institute of Neurological Diseases and Stroke, the Office of Rare Diseases and the National Institute of Diabetes, and Digestive and Kidney Diseases. Other sponsors included the BASF Corporation, BodyBio Corporation, Laxdale, Ltd., Martek Biosciences, Inc., Mead Johnson Nutritionals, Nordic Naturals, Ocean Nutrition Canada, Ltd., OmegaTech, Inc., Roche Vitamins, Inc., Ross Products Div. Abbott Laboratories, Scientific Hospital Supplies and United Leukodystrophies Foundation.

Recent basic and clinical research results indicate that long chain omega-3 polyunsaturated fatty acids (PUFA) such as eicosapentaenoic acid (EPA, 20:5 n-3); docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid, AA, 20:4n-6, and their derivatives may play important physiologic roles in mood and neurodegenerative disorders. Examples are bipolar disorder and unipolar depression; schizophrenia; brain developmental disorders (such as peroxisomal biogenesis disorders, autism and attention deficit-hyperactivity disorder); neurodegenerative diseases of aging including Alzheimer�s disease and brain cancers. The specialized expertise required for working with fatty acids rendered the establishment of this resource imperative. The specialized expertise provided by this Consortium is required for understanding some of the issues highlighted at the above workshop. For example, general areas identified as areas in need of further research are a) fatty acid transport through membranes such as the cerebrovascular endotheliun or blood-brain barrier (BBB) in the developing and mature brain, b) shuttling of fatty acids among the BBB, oligodendrocytes, astrocytes and neurons; c) intermediary metabolism of fatty acids, especially essential PUFA, in oligodendrocytes, astrocytes and neurons in the developing and adult brain; d) brain functions of PUFA including possible role in signal transduction; e) development of new non-invasive methods for quantitation of PUFA and phospholipids in the live human brain by use of animal models of disease; f) diagnosis of disease states and profiling of PUFA in the liver, plasma, erythrocyte membranes and the brain; e) assessment of potential preventive and therapeutic interventions in the above and other disease, etc. (Link to "Agenda, Summary and Recommendations for Future Research" derived from the above-mentioned workshop).

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