CZJ@nihcu.bitnet (04/13/89)
Attached is the Table of Contents and Items of Interest
from the NIH Guide to Grants and Contracts
for 04/14/89.
Jim Cassatt
-------------------
Vol. 18, No. 13, April 14, 1989
NOTICES
EXTRAMURAL RESEARCHERS' FINANCIAL CONFLICTS OF INTEREST MEETING ..(84/137)... 1
National Institutes of Health
Alcohol, Drug Abuse, and Mental Health Administration
Index: NATIONAL INSTITUTES OF HEALTH, ALCOHOL, DRUG ABUSE,
MENTAL HEALTH
DATED ANNOUNCEMENTS (RFPs AND RFAs)
PHASE II-B RANDOMIZED CONTROLLED STUDY OF TISSUE PLASMINOGEN
ACTIVATOR FOR ACUTE STROKE - COORDINATING CENTER (RFP) ..........(143/179)... 1
National Institute of Neurological Disorders and Stroke
Index: NEUROLOGICAL DISORDERS, STROKE
RESEARCH ON PATHOGENESIS OF LYME BORRELIOSIS (LYME DISEASE) (RFA) ........... 2
National Institute of Allergy and Infectious Diseases (182/281, 1044/1320)
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Index: ALLERGY, INFECTIOUS DISEASES, ARTHRITIS,
MUSCULOSKELETAL AND SKIN DISEASES
ONGOING PROGRAM ANNOUNCEMENTS
ALCOHOLISM TREATMENT: MATCHING CLIENTS TO TREATMENT ............(287/370)... 3
National Institute on Alcohol Abuse and Alcoholism
Index: ALCOHOL ABUSE, ALCOHOLISM
GENE THERAPIES FOR AIDS ........................................(373/523).... 4
National Institute of Allergy and Infectious Diseases
Index: ALLERGY, INFECTIOUS DISEASES
BASIC AND CLINICAL RESEARCH ON NORMAL AND IMPAIRED ORAL-MOTOR
FUNCTION .......................................................(526/724).... 6
National Institute of Dental Research
National Institute on Deafness and Other Communicative Disorders
Index: DENTAL RESEARCH, DEAFNESS, COMMUNICATIVE DISORDERS
SENSE OF CONTROL OVER THE LIFE COURSE ..........................(727/1035)... 9
National Institute on Aging
National Institute of Child Health and Human Development
Index: AGING, CHILD HEALTH, HUMAN DEVELOPMENT
NOTICES
EXTRAMURAL RESEARCHERS' FINANCIAL CONFLICTS OF INTEREST MEETING
P.T. 34; K.W. 1014006
National Institutes of Health
Alcohol, Drug Abuse, and Mental Health Administration
The National Institutes of Health (NIH) and the Alcohol, Drug Abuse, and
Mental Health Administration (ADAMHA) are in the process of developing
appropriate further guidance concerning financial conflicts of interest for
investigators receiving Government funds. An open meeting will be held on
June 27 and 28, 1989, in Masur Auditorium of the Warren G. Magnuson Clinical
Center at NIH to provide opportunity for comments from all parties. All
interested parties are encouraged to attend this meeting or to submit written
comments. You may submit these comments to:
Dr. Katherine L. Bick
Deputy Director for Extramural Research
National Institutes of Health
Shannon Building, Room 144
Bethesda, Maryland 20892
As discussed in the January 20 issue of the NIH Guide for Grants and Contracts
(Vol. 18, No. 2), there are growing expressions of concerns about
circumstances that might affect investigators' objectivity, or where
researchers might unduly influence, or might be perceived to influence,
NIH/ADAMHA-funded R&D projects in directions favorable to personal financial
interests of themselves, their spouses, children, close professional
associates, or organizations where they have appointments or other
relationships.
A variety of topics on real, or perceived, conflicts of interest will be
discussed at the June 27-28 meeting, such as whether investigators and
consultants participating in NIH/ADAMHA-funded studies should hold financial
interests in organizations or entities that produce drugs, devices, or other
interventions that are evaluated under those awards. Following this meeting,
NIH/ADAMHA intend to develop appropriate guidance for such relationships.
Guidelines would seek to clarify pertinent types of research situations and
personal financial interests, in accord with the PHS Grants Policy Statement,
January 1, 1987, revision, concerning Standards of Conduct for Employees for
awardee organizations, and to define appropriate distributions of governance
between NIH/ADAMHA and awardee organizations. Points to consider in such
guidance include requirements for disclosure, approval, and/or restrictions in
certain situations as well as possible exceptions to restrictions to permit
investigators with unusual skills and expertise to conduct studies which might
otherwise be proscribed. (These guidelines should not concern financial
benefits resulting from logical steps in product research/development/testing
under NIH awards, e.g., Small Business Innovation Research.) The proposed
meeting is designed to elicit comment from concerned and interested
individuals and institutions prior to development of general guidelines; we
invite broad attendance.
Further information concerning this meeting, including planned discussion
topics, will be published in the NIH Guide for Grants and Contracts in May.
RESEARCH ON PATHOGENESIS OF LYME BORRELIOSIS (LYME DISEASE)
RFA AVAILABLE: 89-AI-14
P.T. 34; K.W. 0715125, 0715010, 0715026, 0710070, 0755020, 0765033
National Institute of Allergy and Infectious Diseases
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Letter of Intent Date: June 1, 1989
Application Receipt Date: August 1, 1989
The National Institute of Arthritis and Musculoskeletal and Skin Diseases
(NIAMS) and the National Institute of Allergy and Infectious Diseases (NIAID)
announce the availability of an RFA for funding Research on Pathogenesis in
Lyme Borreliosis (Lyme disease). This RFA (available upon request) invites
applications for funding of research that will increase our understanding of
interactions between Borrelia burgdorferi and the human host. Increased
knowledge in this area will result in substantial improvements in diagnosis
and chemotherapy and provide the basis for the development of an effective
vaccine. Research projects involving use of tissue culture, animal models,
human subjects, molecular techniques and other experimental approaches may be
focused upon one or more of the following:
o Identification and characterization of bacterial factors that act
as virulence and colonization factors.
o Identification and characterization of antigenic and immunogenic
determinants presented to the host. The role of antigenic
variation in pathogenicity. The mechanism of antigenic variation.
o The nature of the immune response to B. burgdorferi? The
relationships between the cell-mediated and humoral responses to B.
burgdorferi. Characterization of host reactions; protective versus
non-protective, specific (to B. burgdorferi) versus non-specific.
Classes of immunoglobulins produced in response to infection.
o Characterization of the course of infection after B. burgdorferi
enters the human host. Identification of organ systems and tissues
that are infected and/or inflamed. Characterization of specific
tissue tropisms.
o Characterization of inflammatory responses in relation to the
various clinical manifestations associated with Lyme borreliosis.
The roles of cytokines in inflammatory responses in this disease.
o Histopathologic studies of early and late manifestations of the
disease.
o The role of host immunogenetic determinants in susceptibility to
the disease and its various manifestations.
o Development of animal and/or tissue culture models that can be used
to obtain insights or answers to the above questions.
Vol. 18, No. 13, April 14, 1989 - Page 2
o Development of an improved culture medium that will allow
maintenance of B. burgdorferi in a virulent form with greater
maximum population density.
o Development of a genetic transfer system in B. burgdorferi.
o Comparison of pathogenesis of Lyme borreliosis with that of other
spirochetal diseases such as syphilis and relapsing fever.
Applicants may include several of the above areas in their research proposals.
Applicants are encouraged to consider other avenues of investigation that
would be appropriate to the goals of this RFA as well.
Awards will be made as individual research project (R01) grants. Domestic
universities, medical colleges, hospitals, laboratories and other public or
private research institutions, including State and local government units, are
eligible to apply for funding. Awards under this announcement to foreign
institutions will be made only for research of unusually high merit, need and
promise, and in accordance with Public Health Service policy governing such
awards.
This is a one-time solicitation for proposals. Ten to 15 awards may be funded
on the basis of merit and availability of funds.
The full RFA may be obtained from:
Robert L. Quackenbush, Ph.D.
Vector-Borne Bacterial Diseases Program Officer
Microbiology and Infectious Diseases Program, NIAID
Westwood Building, Room 736
Bethesda, Maryland 20892
Telephone: (301) 496-7728
or
Steven J. Hausman, Ph.D.
Deputy Director, Extramural Program
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Westwood Building, Room 403
Bethesda, Maryland 20892
Telephone: (301) 496-7495
GENE THERAPIES FOR AIDS
P.T. 34; K.W. 0745032, 0715008, 0755025, 0755060, 1002008, 1002045, 0755020
National Institute of Allergy and Infectious Diseases
BACKGROUND INFORMATION
The National Institute of Allergy and Infectious Diseases (NIAID) is playing a
central role in the investigation of Acquired Immunodeficiency Syndrome
(AIDS). Research efforts directed toward the pathogenesis, prevention and
treatment of the disease and its sequelae have intensified. The NIAID has
undertaken a lead role in organizing scientists into National Cooperative Drug
Discovery Groups for the Treatment of AIDS (NCDDG/AIDS). NCDDG/AIDS are
comprised of scientists from academic, non-profit, and commercial
organizations that interact as a unit, with NIAID support, to conduct
preclinical research aimed at the discovery of agents which can be used in the
treatment of AIDS. Samples of the research areas currently being investigated
by NCDDG scientists include molecular biology of HIV and SIV; development of
unique cell culture assays, biochemical screens and small animal models;
discovery of new lead compounds and biologics; rational drug design; X-ray
crystallography of proteins and drugs; characterization and isolation of
natural products; development of delivery systems for new drugs; and
development of viral vectors for delivery of anti-viral genes, and antisense
nucleic acids. Since the inception of the NCDDG/AIDS in 1986, three potential
therapies have been discovered and developed. One anti-HIV compound,
Vol. 18, No. 13, April 14, 1989 - Page 4
recombinant soluble CD4 (Biogen, Inc.) has already entered clinical trial and
two nucleosides, [azidouridine (CS-87) and dideoxydidehydrothymidine (d4T) are
expected to enter clinical trial in 1989. Other potential therapeutics
identified through the comprehensive efforts of the NCDDG are in earlier
states of preclinical development.
The NIAID, through the Developmental Therapeutics Branch of the AIDS Program,
will soon launch an NCDDG/OI program to encourage collaborative efforts to
discover new therapies targeted to the opportunistic infections associated
with AIDS. NIAID also facilitates the acquisition of information on any drug
that shows potential in the treatment of HIV infection, fills gaps in the drug
development process, provides ancillary information on the rationale of the
drug in animal retroviral models, and assists in the transition of promising
therapies into clinical trials in NIAID's AIDS Clinical Trial Group program.
The NIAID now wishes to expand the areas of investigator-initiated research
currently being funded. This Program Announcement solicits applications from
investigators who wish to play an active role in defining the direction of
such research. While no funds are specifically set aside for funding grants
submitted in response to this Program Announcement, the NIAID regards
additional high quality research in this area of high priority.
OBJECTIVES AND SCOPE
The objectives of this Program Announcement are to stimulate research on: (i)
development of viral vectors encoding anti-HIV peptides or antisense RNA, and
(ii) evaluation of the potential of these vectors to block HIV expression
using in vitro systems and small animal models.
The potential of gene therapy in the treatment of human genetic diseases is
under intense study. Several viral vectors, including retroviruses,
adenoviruses, herpes simplex virus and helper-dependent viruses have been
established and tested in vitro. Recombinant retroviruses have also been
delivered in vivo via the hemopoietic system (mice, dogs, monkeys, ferrets) or
via implants of retrovirus-transformed fibroblasts, hepatocytes or endothelial
cells. Similar vectors are now being considered for gene therapy in humans.
Indeed, the infusion of mature lymphocytes transformed ex vivo with a
retrovirus vector carrying a reporter (neomycin) gene in cancer patients is
underway. DNA vectors with a broad host range and a large insert capacity,
such as autonomously replicating herpes simplex amplicons, may also prove
suitable for gene therapy. Variants with specific cell tropism are also
available, expanding the potential of targeting genes to specific cell
populations.
Additional studies are needed to improve existing systems and to design novel
transfer modalities applicable to the future treatment of HIV-infected
individuals. For example, it may be possible to achieve targeted delivery to
HIV-infected cell populations using novel ligands embedded in the vector's
membrane which are compatible with the cell's surface receptors or markers
(CD4+/gp120). Similarly, specific expression within target cells (T4,
monocyte/macrophage, others) may be feasible using cell type specific
promoters or promoters inducible only in a desired cell population. The
potential risk that may be associated with the in vivo use of these vectors
should be assessed. For example, integration of provirus DNA may result in
insertional mutagenesis, perturbation of cellular gene expression or
activation of cellular oncogenes. These possibilities should be analyzed in
in vitro systems.
Evaluations of various vectors in small animal studies would yield important
information on the applicability of these strategies to in vivo delivery.
Several animal models amenable to these studies are being developed
[transgenic mice or rabbits harboring HIV genetic elements, immunodeficient
mice reconstituted with human immune cells]. Investigators are encouraged to
collaborate with laboratories having these resources. A potentially important
and unique approach to targeted delivery of anti-HIV agents could result.
Results from this research could have broad implications for the treatment of
a variety of infectious, immunological and metabolic diseases.
In summary, NIAID wishes to stimulate research in the following:
o Development of viral vectors encoding anti-HIV peptides or
antisense RNAs,
o Targeting viral vectors to HIV-infected cells using novel ligands,
o Targeting expression in HIV-infected cells using inducible or
cell-type specific promoters, and
Vol. 18, No. 13, April 14, 1989 - Page 5
o Evaluation of the in vivo applicability of such vectors using small
animal retroviral models.
The approaches outlined above are not intended to be comprehensive or
required. Any investigation on the use of vectors for the in vitro or in vivo
(small animal models) transfer of a gene expressing antisense RNA or any other
gene with potential anti-HIV activity are encouraged under this Program
Announcement.
METHOD OF APPLICATION
Use the standard research Grant Application Form PHS 398 (Rev. 9/86). For
purpose of identification and processing, the words "Gene Therapies for AIDS"
should be typed in item 2 on the face page of the application. The receipt
dates are May 1 and September 1, 1989, and January 1, 1990. In order to
comply with the expedited review for AIDS applications, mail the complete
application and twenty-four (24) exact copies to:
DRG AIDS Coordinator
Westwood Building Room 240
National Institute of Health
Bethesda, Maryland 20892**
REVIEW PROCEDURES AND CRITERIA
Support for this program will be through the traditional research grant.
Applications will be reviewed by the appropriate Study Sections designated by
the Division of Research Grants. A second review will be made by an
appropriate National Advisory Council. Review criteria will be the same as
those for traditional research grant applications.
INQUIRIES
Inquiries of a scientific nature may be addressed to:
Nava Sarver, Ph.D.
Senior Scientist
Targeted Drug Development Section
Developmental Therapeutics Branch
AIDS Program, NIAID, NIH
6003 Executive Boulevard
Rockville, Maryland 20892
Telephone: (301) 496-8197