Innovative thinking understands and overcomes barriers. Whether the obstacle is social, environmental, geographic or systemic, innovation finds ways to remove or bypass it to achieve a goal. At American Leprosy Missions, we seek to accelerate solutions that will cure, care for, and end neglected tropical diseases (NTDs), solutions that overcome existing barriers. This fall, we celebrated the elimination of another barrier: a 9-14 month process to analyze how leprosy protein mutations impact drug resistance. A process that can now be completed in a matter of seconds.
Encountering an Obstacle in Leprosy Treatment
Dr. Sundeep Chaitanya, American Leprosy Missions' director of innovation and research, grew up in a leprosy hospital, observing firsthand the disease's devastation and the importance of timely treatment. Later, as a researcher in south India, Dr. Chaitanya processed DNA samples from leprosy patients who didn't respond to multi-drug therapy (MDT). Resistance to MDT is a serious concern, since it's the only existing cure for people affected by leprosy. Unfortunately, determining drug resistance is a time-consuming process: collecting samples, isolating relevant genes, then waiting on specialists to analyze the DNA.
As part of the DNA analysis for these patients, Dr. Chaitanya would identify protein mutations causing drug resistance and send a result to the clinics. However, only a handful of mutations were catalogued, so there was no available guidance on how to treat people experiencing undocumented mutations.
Dr. Chaitanya remembers these moments: "When I sent the reports with new mutations to the clinics, I many times heard the question, 'Sundeep, what do we do now?'"
New Tool to Analyze Mutations
Today, after years of work, Dr. Chaitanya has developed an incredible new tool for other researchers and clinicians to analyze mutations. American Leprosy Missions is proud to announce the launch of the HARP (Hansen's disease Antimicrobial Resistance Profiles) database, a collaboration with Sir Thomas Blundell's group in the Department of Biochemistry at the University of Cambridge. HARP catalogs all 80,902 mutations, showing instantly how mutant proteins impact MDT therapy.
A complete reference like HARP is an invaluable resource for those diagnosing and treating drug-resistant leprosy, like Dr. Chaitanya did as a researcher. Using HARP, clinicians and scientists can immediately see how each protein mutation leads or doesn't lead to MDT resistance, rather than working for 9-14 months to determine the outcome of new mutations. While there is still work to do in adapting MDT treatment for people affected by a mutation, HARP streamlines the analysis process in a way never seen before.
“Business as usual” will not beat NTDs like leprosy, so we continue to develop new tools that will have a positive impact for people affected. To learn more about this newest innovative step, visit the HARP database at https://harp-leprosy.org/home or read the article, HARP, a database of structural impacts of systematic missense mutations in drug targets of Mycobacterium leprae published in the Computational and Structural Biotechnology Journal (IF 6.018).
Jessica Mussro
Communications Coordinator
American Leprosy Missions