A Topical Nrf Activator for Oral Mucositis
Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R43DE026086-01A1
Agency Tracking Number: R43DE026086
Amount:
$229,248.00
Phase:
Phase I
Program:
SBIR
Solicitation Topic Code:
NIDCR
Solicitation Number:
PA15-269
Timeline
Solicitation Year:
2015
Award Year:
2017
Award Start Date (Proposal Award Date):
2017-03-15
Award End Date (Contract End Date):
2018-12-14
Small Business Information
12635 E MONTVIEW BLVD STE 130, Aurora, CO, 80045-7336
DUNS:
079599519
HUBZone Owned:
N
Woman Owned:
N
Socially and Economically Disadvantaged:
N
Principal Investigator
Name: BROOKS HYBERTSON
Phone: (720) 301-4579
Email: hybertson@gmail.com
Phone: (720) 301-4579
Email: hybertson@gmail.com
Business Contact
Name: BROOKS HYBERTSON
Phone: (720) 301-4579
Email: brooks@pathwaysbio.com
Phone: (720) 301-4579
Email: brooks@pathwaysbio.com
Research Institution
N/A
Abstract
We propose to develop a topical formulation for preventing or treating oral mucositis Oral
mucositis is a common and harmful side effect of radiation therapy and chemotherapy in cancer
patients that affects nearly patients in the US annually and can be dose limiting
impairing the clinical ability to continue the otherwise needed therapy and that also greatly
impacts the patientandapos s quality of life due to pain loss of function and increased infections There
remains a huge unmet clinical need with a market value of approximately US$ billion Despite
the high frequency of oral mucositis in both radiation and chemotherapy patients its negative
impact on the clinical ability to apply sufficient doses of these therapies to patients its
debilitating nature on the affected patients and the associated high financial costs of oral
mucositis per patient there is no effective intervention currently available for the majority of
patients at risk One promising approach is protecting the oral mucosal cells through the
application of topical agents that upregulate cell protection mechanisms in the oral mucosa prior
to radiation therapy We are developing a therapeutic agent PB that activates the Nrf
NFE L Nuclear Factor Erythroid Like cell signaling pathway which in turn upregulates
radioprotective antioxidant and anti inflammatory genes and is a promising candidate for
preventing or treating oral mucositis We have examined the Nrf activating properties of PB
in a variety of cell types have identified and tested a backup agent from the same molecular
class in case PB fails during development and have created a prototype of the intended
aqueous oral formulation of PB Briefly our preliminary data supports the hypothesis the
PB is a potent Nrf activator in a variety of cancer and normal human cell types and is a
strong candidate for development as a topical oral mucositis drug In Phase I of this multiphase
project we will create and test a topical formulation of PB examine Nrf activation and gene
expression caused by the PB formulation in cultured human oral mucosal cells and perform
efficacy studies of the topically applied PB formulation in a hamster model of radiation
induced oral mucositis Our preliminary data suggests that the likelihood for success is high in
this Phase I project and we are planning to continue the work in a Phase II SBIR project
including expansion into fractionated radiation and chemotherapy models of oral mucositis and
ADME and toxicological measurements as we develop PB in an attempt to meet the unmet
need for new therapeutic approaches to oral mucositis Development of safe effective topical
treatment that upregulates cell protection mechanisms in the oral mucosa prior to or after
radiation or chemotherapy would be a significant advancement Oral mucositis is a harmful and painful side effect of radiation therapy and chemotherapy
that affects nearly half a million cancer patients in the US each year and that can be
dose limiting impairing the clinical ability to continue the otherwise needed No effective
treatments are available and there is a great unmet need to develop new therapeutic
approaches to oral mucositis In the present study a new topical agent will be tested
and developed to pursue the promising approach of protecting the oral mucosal cells
through the application of topical agents that upregulate cell protection mechanisms in
the oral mucosa prior to radiation or chemotherapy * Information listed above is at the time of submission. *