This proposal seeks to establish a development program to transition an experimental Transdermal Tuberculosis Skin Test into a commercial product. This technology has already demonstrated a remarkable ability to specifically identify AFB+ TB patients by adminstering a small amount of a TB protein (MPB64) to the skin and monitoring for an erythemic skin response. PPD+ symptomless individuals are non-reactive to the protein. The MPB-64 Transdermal Patch was applied to sixty-two patients, 49 with sputum-positive active disease and 13 who had completed TB chemotherapy, and 28 non-TB but tuberculin-positive controls. The results were read at 72h. The sensitivity of the Transdermal Patch was 87.8 percent, efficacy 92.9 percent, and specificity 100 percent. The thirteen TB patients who had each completed 6 months of TB chemotherapy showed different reactions to MPB64 patch test: those who had completed chemotherapy less than 4 months before testing were positive; 50 percent of patients who completed chemotherapy 5 months prior were positive; and those who had completed chemotherapy 7 and 8 months before were negative. All the non-TB controls with positive tuberculin tests were negative to the MPB-64 Transdermal Patch, even at the highest protein dose tested. This test may be a useful method to distinguish active TB patients from TB-infected but asymptomatic individuals. The current version of the technology is a research grade patch. This proposal will outline a development pathway to improve product packaging, ease of use and product stability. Initial efforts will be to characterize a unique animal model for use in examining component materials and technologies.
Our specific aims are 1. Validate an animal model to test variables in the formulation and transdermal delivery of the skin test antigen, 2. Establish the most cost effective source of MPB64, 3. Establish the best packaging / delivery technology for the patch, 4. Establish animal test procedures for toxicity, product release and to test product stability. Phase II aims include optimizing protein production and manufacturing scale up, and performance of clinical trials for product registration.
The
would be to develop a patch test for diagnostic screening of active cases of tuberculosis by using transdermal delivery of MPB64 protein. The patch test could be used in place of other screening tests, such as the PPD skin test or the AFB smear, as a means of diagnosing patients with active tuberculosis.
