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 Scientists discover how the molecule-sorting station in our cells is formed and maintained
18.11.2019 | Tokyo University of Science

nachricht Pesticides: Improved effect prediction of low toxicant concentrations
18.11.2019 | Helmholtz Centre for Environmental Research - UFZ

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Images from NJIT's big bear solar observatory peel away layers of a stellar mystery

An international team of scientists, including three researchers from New Jersey Institute of Technology (NJIT), has shed new light on one of the central mysteries of solar physics: how energy from the Sun is transferred to the star's upper atmosphere, heating it to 1 million degrees Fahrenheit and higher in some regions, temperatures that are vastly hotter than the Sun's surface.

With new images from NJIT's Big Bear Solar Observatory (BBSO), the researchers have revealed in groundbreaking, granular detail what appears to be a likely...

Im Focus: New opportunities in additive manufacturing presented

Fraunhofer IFAM Dresden demonstrates manufacturing of copper components

The Fraunhofer Institute for Manufacturing Technology and Advanced Materials IFAM in Dresden has succeeded in using Selective Electron Beam Melting (SEBM) to...

Im Focus: New Pitt research finds carbon nanotubes show a love/hate relationship with water

Carbon nanotubes (CNTs) are valuable for a wide variety of applications. Made of graphene sheets rolled into tubes 10,000 times smaller than a human hair, CNTs have an exceptional strength-to-mass ratio and excellent thermal and electrical properties. These features make them ideal for a range of applications, including supercapacitors, interconnects, adhesives, particle trapping and structural color.

New research reveals even more potential for CNTs: as a coating, they can both repel and hold water in place, a useful property for applications like printing,...

Im Focus: Magnets for the second dimension

If you've ever tried to put several really strong, small cube magnets right next to each other on a magnetic board, you'll know that you just can't do it. What happens is that the magnets always arrange themselves in a column sticking out vertically from the magnetic board. Moreover, it's almost impossible to join several rows of these magnets together to form a flat surface. That's because magnets are dipolar. Equal poles repel each other, with the north pole of one magnet always attaching itself to the south pole of another and vice versa. This explains why they form a column with all the magnets aligned the same way.

Now, scientists at ETH Zurich have managed to create magnetic building blocks in the shape of cubes that - for the first time ever - can be joined together to...

Im Focus: A new quantum data classification protocol brings us nearer to a future 'quantum internet'

The algorithm represents a first step in the automated learning of quantum information networks

Quantum-based communication and computation technologies promise unprecedented applications, such as unconditionally secure communications, ultra-precise...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

First International Conference on Agrophotovoltaics in August 2020

15.11.2019 | Event News

Laser Symposium on Electromobility in Aachen: trends for the mobility revolution

15.11.2019 | Event News

High entropy alloys for hot turbines and tireless metal-forming presses

05.11.2019 | Event News

 
Latest News

Volcanoes under pressure

18.11.2019 | Earth Sciences

Scientists discover how the molecule-sorting station in our cells is formed and maintained

18.11.2019 | Life Sciences

Hot electrons harvested without tricks

18.11.2019 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>