Cigarette smoking is the most common preventable cause of morbidity and mortality in the United States. Over the past 20 years, several effective treatments, including varenicline, bupropion and nicotine replacement treatments (NRT, such as nicotine gum or patches) have been developed. Despite significant efforts, the overall success of these treatments for smoking cessation is about 10%. Although there are number of potential barriers to increasing the success rate of these treatments, one of the most vexing is the lack of methods to objectively quantify treatment success/reduction of harm and provide evidence-based positive feedback to patients. Developing, validating, and commercializing this next-generation technology to exactly quantify the amount of smoking cessation success/harm reduction is Behavioral Diagnostic's overall goal for this multi-phase SBIR study. Currently, two biomarkers of smoking- exhaled carbon monoxide (CO) and (serum, salivary or urinary) cotinine levels exist, but both of these biomarkers have significant limitations as indicators of smoking cessation. Exhaled CO is only useful for detecting smoking within ~12 hours of last use while cotinine levels are insensitive to more remote smoking and are obscured by the use of NRT agents because the nicotine in these agents is also metabolized to cotinine. The latter is a particular problem because the vast majority of patients receiving smoking cessation therapy receive NRT as a primary or adjunctive therapy. Thus, there is both a large potential market and a great need for the development of a new biomarker of smoking that could serve as a more effective clinical assessment tool or be used by pharmaceutical companies to quantify the reduction of harm afforded by the use of a new medication or intervention. Over the past two years, we, and others, have repeatedly demonstrated that demethylation of cg05575921, a CpG residue in the aryl hydrocarbon receptor repressor gene (AHRR) is a sensitive measure of smoking. More recently, we have shown that this methylation at cg05575921 reverts to baseline after cessation of smoking. In this Phase I application, we will use our recently developed real time polymerase chain reaction (RTPCR) test to develop an algorithm describing the relationship of smoking cessation to the reversion of the AHRR methylation signature in DNA from obtained by three methods: venipuncture, easy-to- do finger sticks (i.e. no phlebotomist needed) and easy-to-obtain saliva. The effort will be led by Dr. Terry Osborn, an experienced BioPharma Executive who is also leading our commercialization process, and Drs. Philibert and Madan, the co-inventors on the recently granted patent, who have extensive published experience in the clinical, genetic and epigenetic characteristics of smoking. As a direct result o this project we will develop a formula describing the relationship of abstinence to re-methylation at cg05575921 that can be formally tested in a prospective, blinded Phase II trial of the first epigenetic test for quantitatively determining the success of smoking cessation therapy.

Public Health Relevance

The purpose of this application is to determine whether DNA methylation can be used as a sensitive biomarker of the success of smoking cessation therapy. If successful, the project could lead to an easy-to-use clinical biomarker that could be used by both clinicians and pharmaceutical companies to increase the effectiveness of smoking cessation treatment.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-SBIB-Q (11))
Program Officer
Bough, Kristopher J
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Behavioral Diagnostics, Inc.
Iowa City
United States
Zip Code