Aminosterol Compounds as Therapeutic for Asthma

Project: Research project

Project Details

Description

DESCRIPTION (provided by applicant):Phase II research will emphasize continuing
in vitro and in vivo data collection to identify Genaera aminosterol library
compounds useful in treating atergen-induced respiratory inflammation, with a
focus on asthma. Lead compounds will first be defined using in vitro endpoints
for interference with lymphocyte function, emphasizing the additional
collection of trans-epithelial monolayer barrier penetration data as a
surrogate for possible oral activity. Careful pharmacokinetic and activity data
measurements for lead compounds in an Aspergillus fumigatus spore-induced
murine model of airway inflammation using both oral and intratracheal routes of
aminosterol administration will subsequently be taken to select a few
aminosterols for formal preclinical development. These compounds will be
compared to the water soluble lead compounds MSI-1 432 and MSI-f 828 shown
active in phase I research for intratracheal delivery, while discovery of an
orally active aminosterol is given priority in parallel experimentation.
Preparation and formulation of a single lead aminosterol to GMP standards will
then be rapidly instituted for delivery by the preferred route of
administration, along with necessary supporting analytical method development,
and a first acute rat toxicity GLP study will be initiated as the first of a
series of preclinical safety studies to support use in humans. The eventual
goal is to enter human clinical trials in asthma patients by 2004 with an
orally delivered aminosterol emerging from the phase Il SBIR research.
PROPOSED COMMERCIAL APPLICATION:
Asthma affects more than 14?15 million U.S. citizens" 5 million of whom are children, and more than 5,000 die of asthmatic disease each year. The health related costs of asthma are estimated for the year 2000 to exceed $14.5 billion, and asthma (and asthma costs) are on the rise among inner city residents. There is a significant need for better and more novel treatments for asthma, notably those with fewer side effects and that are easier for patients to use. Aminosterols are a new class of anti-inflammatory agents discovered by Genaera Corporation that are preferentially active with Th2-type T cells and that may offer several advantages to asthma patients, including the ability to self-administer.
StatusFinished
Effective start/end date3/1/022/28/05

Funding

  • National Heart, Lung, and Blood Institute: $152,967.00
  • National Heart, Lung, and Blood Institute: $422,306.00

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