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Progress novel assets (one FIH start) for non-tubercular mycobacteria that may act synergistically with bedaquiline and cytochrome bc drugs

Objective

Non-tuberculous mycobacteria, such as Mycobacterium avium complex (MAC) and Mycobacterium abscessus, cause lung diseases resembling TB, mainly in immune-compromised patients or patients suffering from other lung diseases (e.g. cystic fibrosis). The incidence and prevalence of lung diseases caused by NTM are increasing worldwide. Importantly, in the US and Japan, as well as in other areas of the world where TB has declined, NTM disease is already at least three times more prevalent than TB. Treatment of NTM diseases relies on antibiotic combinations, however the drugs active against NTM are rather few and mainly different than those active against TB. These NTM treatments for the most common species (MAC and M. abscessus) are much less active than the current anti-TB regimen is for TB treatment. It is often necessary to administer antibiotic combinations for at least 12-24 months. The long and complex drug regimen that is currently recommended as a treatment against NTM-caused diseases carries the risk of inducing resistance in NTM. Several studies have already shown the existence and emergence of multidrug resistant NTM. The overall objective of RESPIRI-NTM is to find new drug candidates as potential components of a new, more efficient combination drug regimen against NTM that is less prone to resistance and allows shortening of treatment duration for NTM and multidrug-resistant NTM. Such a drug combination will synergistically target the energy metabolism of NTM or complementary targets. To achieve this, we will advance recently discovered inhibitors of the mycobacterial respiratory pathway. In addition, we will perform a novel, phenotypic screen in order to identify novel targets in NTM. Finally, we will also target host-factors that are essential for the intracellular survival of NTM. Together, we present a comprehensive plan to find novel strategies to combat non-tuberculous mycobacteria, shorten treatment time and reduce chances of drug resistance.

Call for proposal

H2020-JTI-IMI2-2018-16-single-stage
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Funding Scheme

IMI2-RIA - Research and Innovation action

Coordinator

ACADEMISCH ZIEKENHUIS LEIDEN
Address
Albinusdreef 2
2333 ZA Leiden
Netherlands
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 1 570 226,25

Participants (8)

UNIVERSITEIT LEIDEN
Netherlands
EU contribution
€ 766 250
Address
Rapenburg 70
2311 EZ Leiden
Activity type
Higher or Secondary Education Establishments
UNIVERSITEIT ANTWERPEN
Belgium
EU contribution
€ 1 191 325
Address
Prinsstraat 13
2000 Antwerpen
Activity type
Higher or Secondary Education Establishments
SORBONNE UNIVERSITE
France
EU contribution
€ 726 750
Address
21 Rue De L'ecole De Medecine
75006 Paris
Activity type
Higher or Secondary Education Establishments
MEDIZINISCHE UNIVERSITAET WIEN
Austria
EU contribution
€ 848 750
Address
Spitalgasse 23
1090 Wien
Activity type
Higher or Secondary Education Establishments
KOBENHAVNS UNIVERSITET
Denmark
EU contribution
€ 260 067,50
Address
Norregade 10
1165 Kobenhavn
Activity type
Higher or Secondary Education Establishments
JANSSEN PHARMACEUTICA NV
Belgium
EU contribution
€ 0
Address
Turnhoutseweg 30
2340 Beerse
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
MITOLOGICS
France
EU contribution
€ 153 060
Address
Avenue Gaston Roussel 102
93230 Romainville
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
FFUND BV
Netherlands
EU contribution
€ 171 555
Address
Barbara Strozzilaan 101
1083 HN Amsterdam
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)