A novel asthma drug candidate targeting the GABAergic system in lung inflammation

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41HL147658-01
Agency Tracking Number: R41HL147658
Amount: $224,756.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: NHLBI
Solicitation Number: PA18-575
Timeline
Solicitation Year: 2018
Award Year: 2019
Award Start Date (Proposal Award Date): 2019-05-01
Award End Date (Contract End Date): 2021-04-30
Small Business Information
3074 LINNERUD DR, Stoughton, WI, 53589-3285
DUNS: 080109555
HUBZone Owned: N
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 ALEXANDER ARNOLD
 (414) 229-2612
 arnold2@uwm.edu
Business Contact
 ALEXANDER ARNOLD
Phone: (415) 235-7642
Email: arnold.pantherics@gmail.com
Research Institution
 UNIVERSITY OF WISCONSIN MILWAUKEE
 PO BOX 340
MILWAUKEE, WI, 53201-0340
 Nonprofit college or university
Abstract
The proposed research will advance preclinical characterization and validation of a novel drug for asthmaA growing body of research has uncovered functional gamma amino butyric acid type A receptorGABAARsignaling in non neuronal cellsOur research has demonstrated that ligands activating GABAAR subtypes located on airway smooth muscle and immune cells reduce airway hyper responsivenessAHRand inflammation when orally administered in animal asthma modelsThe significance of this innovation is a novel receptor targeting and drug design strategy for a safe and effective oral asthma treatmentInnovative new treatments are needed to cost effectively control symptomsreduce adverse effectsimprove compliance by avoiding inhaler useand provide better solutions for steroid resistant asthma patientsThe long term goal of this research is approval of a first in class oral drug for asthmaThe objective of the Phase I STTR contract is optimization of lead compound MIDDvia a formulation that enhances oral bioavailability as determined by drug pharmacokineticsPKmetabolismand clearanceTo establish compound safetya battery of safety pharmacology testing will be conducted using approaches set forth in regulatory guidelinesOur central hypothesis based on preliminary data is that therapeutic levels of MIDDare readily achieved in the lung and GABAARs can be targeted safely with anionic ligands for asthma treatmentThe rationale for these nonclinical studies is the need to identify a formulation of MIDDsuitable for clinical testing and corresponding drug exposure and safety verification to estimate an initial safe starting dose and dose range for future human trialsOur hypothesis will be tested within three Specific AimsIdentify the most bioavailable polymorphic form of MIDDand its saltsestablish MIDDsafety by safety pharmacology testingandidentify and investigate possible MIDDmetabolitesThe significance of this research is advancement of safe and effective drug candidate that controls asthma symptomsavoids steroid resistanceand improves complianceFurthermoreit is expected that development of MIDDwill lay the foundation for future drug research that targets peripheral GABAARs for other immune inflammatory diseases in addition to asthmaThe innovation of this research is the validation of a new therapeutic target for asthma common to airway smooth muscle and immune cells that can be modulated with a single small molecule to control airway hyperresponsiveness and inflammationtwo pathophysiological hallmarks of asthmaThis research will expand crosscutting knowledge of a unified paracrine GABAergic system in the lung that can be applied to other lung disordersThe proposed research is relevant to public health because it seeks to advance a novel treatment for asthmaa disease afflicting approximatelymillion people in the USoverof the populationand incurring annual health care costs of over $billionInnovative therapies are needed to improve symptom control and quality of lifereduce adverse effectsimprove treatment complianceand control costsThe research is relevant to the NIH mission by uncovering generalizable knowledge of GABAA receptor signaling in the lung and applying this knowledge to the design and development of a new oral medication to treat asthma patients

* Information listed above is at the time of submission. *

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