Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Buruli Ulcer: Promising New Drug Candidate Against a Forgotten Disease

19.12.2018

Buruli ulcer is a neglected tropical disease (NTD) resulting in debilitating skin lesions, disabilities and stigmatisation. The current antibiotic treatment is long and has severe adverse side effects. Researchers from the Swiss Tropical and Public Health Institute (Swiss TPH) together with colleagues from Singapore have discovered a highly effective compound against Buruli ulcer which has the potential to become a powerful alternative to the existing treatment options. Results were published today in the peer-reviewed journal Nature Communications.

Buruli ulcer – one of the most neglected among the NTDs – is a debilitating and stigmatising disease. Affecting mainly children in West and Central Africa, the chronic disease results in devastating skin lesions and can lead to permanent disfigurement and long-term disabilities.


Buruli Ulcer

Hubert Vuagnat

Buruli ulcer is caused by Mycobacterium ulcerans which belongs to the same family of bacteria that cause tuberculosis (TB) and leprosy. M. ulcerans is found in the environment and, despite considerable research efforts, the mode of transmission of the bacteria to humans remains unclear.

Difficult treatment with adverse side effects

... more about:
»TB »bacterium »mycobacterium »skin lesions »ulcer

Traditionally, the skin lesions caused by Buruli ulcer have been removed by wide surgical excision. Since 2004, the World Health Organization (WHO) also recommends treatment with a combination of antibiotics: oral rifampicin and injected streptomycin. Surgery is often not an accessible option in low-income settings and the combination therapy requires daily visits in health centres over an 8-week period.

More importantly, the antibiotics result in severe adverse side effects with over 20% of treated patients suffering from hearing loss. In addition, fear of the emergence of rifampicin resistance increases the pressure to develop new and better drug treatment regimens.

Highly effective compound discovered

Swiss TPH researchers, together with partner institutions such as the Nanyang Technological University in Singapore, have now discovered a promising compound against Buruli ulcer. The study, which was published today in the peer-review journal Nature Communications, found that compound Q203 (an imidazopyridine amide) is highly effective against Buruli ulcer, both in vitro and in vivo.

“We were very surprised when we saw this high activity. We had previously screened hundreds of compounds that were originally intended for TB drug development and none of the others showed promising activity against Mycobacterium ulcerans,” said Gerd Pluschke, Head of the Molecular Immunology Unit at Swiss TPH.

“Q203, however, is even more effective against Buruli ulcer than the current most active antibiotic rifampicin. Such a new and exquisitely effective drug combined with a second antibiotic may result in a considerably shorter oral treatment regimen with fewer adverse side effects.”

Another advantage of Q203 is that its safety has already been tested in a phase I clinical trial for TB. “That means that as soon as funding can be secured, we will directly test the new compound in Buruli ulcer patients in a phase II trial,” said Pluschke.

Important knowledge on the bacterium established

Comparison of the M. ulcerans genome with other mycobacterial genomes provided an explanation for why this bacterium is so sensitive to Q203. The bacterium seems to be on the way to develop from an environmental organism to a specialised pathogen, which is adapting to live in a more stable environment.

In the course of this evolution, it is reducing the number of active genes, since many cellular functions are only needed by free living environmental organisms. While respiration of the less sensitive TB bacteria relies on two pathways, with only one being blocked by Q203, M. ulcerans has lost the alternative Q203 resistant pathway and cannot persist for longer times in the presence of the drug.

Broad and long-term expertise on Buruli ulcer

Swiss TPH has a long-standing interest and wide-ranging expertise in researching Buruli ulcer. Apart from drug discovery, scientists are also working on heat therapy as an alternative treatment option and first steps have been taken to develop a vaccine. Together with the Foundation for Innovative New Diagnostics (FIND), Swiss TPH is also working on developing a rapid diagnostic test for Buruli ulcer.

“Research, long-term commitment and productive partnerships demonstrate that Swiss TPH can make a meansingful contribution to a deeper understanding of the epidemiology and control of Buruli ulcer and other NTDs,” said Jürg Utzinger, Director of Swiss TPH. Research on Buruli ulcer at Swiss TPH has been supported by the Medicor Foundation and the UBS Optimus Foundation for many years.

About the publication

To conduct this research, Swiss TPH worked with a number of partner institutions, including the Lee Kong Chian School of Medicine at Nanyang Technological University in Singapore.

Scherr N. et al. Targeting the Mycobacterium ulcerans cytochrome bc1:aa3 for the treatment of Buruli ulcer. (2018) Nature Communications. https://doi.org/10.1038/s41467-018-07804-8

Wissenschaftliche Ansprechpartner:

Prof. Dr. Gerd Pluschke, Head of the Molecular Immunology Unit, Swiss TPH, +41 61 284 8235, gerd.pluschke@swisstph.ch

Sabina Beatrice-Matter, Head of Communications, Swiss TPH, +41 61 284 8364, +41 79 737 91 58, sabina.beatrice@swisstph.ch

Danielle Powell | idw - Informationsdienst Wissenschaft
Further information:
http://www.swisstph.ch/

Further reports about: TB bacterium mycobacterium skin lesions ulcer

More articles from Life Sciences:

nachricht Microbes can grow on nitric oxide (NO)
18.03.2019 | Max-Planck-Institut für Marine Mikrobiologie

nachricht Novel methods for analyzing neural circuits for innate behaviors in insects
15.03.2019 | Kanazawa University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Revealing the secret of the vacuum for the first time

New research group at the University of Jena combines theory and experiment to demonstrate for the first time certain physical processes in a quantum vacuum

For most people, a vacuum is an empty space. Quantum physics, on the other hand, assumes that even in this lowest-energy state, particles and antiparticles...

Im Focus: Sussex scientists one step closer to a clock that could replace GPS and Galileo

Physicists in the EPic Lab at University of Sussex make crucial development in global race to develop a portable atomic clock

Scientists in the Emergent Photonics Lab (EPic Lab) at the University of Sussex have made a breakthrough to a crucial element of an atomic clock - devices...

Im Focus: Sensing shakes

A new way to sense earthquakes could help improve early warning systems

Every year earthquakes worldwide claim hundreds or even thousands of lives. Forewarning allows people to head for safety and a matter of seconds could spell...

Im Focus: A thermo-sensor for magnetic bits

New concept for energy-efficient data processing technology

Scientists of the Department of Physics at the University of Hamburg, Germany, detected the magnetic states of atoms on a surface using only heat. The...

Im Focus: The moiré patterns of three layers change the electronic properties of graphene

Combining an atomically thin graphene and a boron nitride layer at a slightly rotated angle changes their electrical properties. Physicists at the University of Basel have now shown for the first time the combination with a third layer can result in new material properties also in a three-layer sandwich of carbon and boron nitride. This significantly increases the number of potential synthetic materials, report the researchers in the scientific journal Nano Letters.

Last year, researchers in the US caused a big stir when they showed that rotating two stacked graphene layers by a “magical” angle of 1.1 degrees turns...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

International Modelica Conference with 330 visitors from 21 countries at OTH Regensburg

11.03.2019 | Event News

Selection Completed: 580 Young Scientists from 88 Countries at the Lindau Nobel Laureate Meeting

01.03.2019 | Event News

LightMAT 2019 – 3rd International Conference on Light Materials – Science and Technology

28.02.2019 | Event News

 
Latest News

Researchers measure near-perfect performance in low-cost semiconductors

18.03.2019 | Power and Electrical Engineering

Nanocrystal 'factory' could revolutionize quantum dot manufacturing

18.03.2019 | Materials Sciences

Long-distance quantum information exchange -- success at the nanoscale

18.03.2019 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>