Injectable anti-malarials revisited: discovery and development of new agents to protect against malaria
Abstract Over the last 15 years, the majority of malaria drug discovery and development efforts have focused on new molecules and regimens to treat patients with uncomplicated or severe disease. In addition, a number of new molecular scaffolds have been discovered which block the replication of the...
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doaj-dbdcceb481fa497fa620c83328de23ba2020-11-25T02:07:02ZengBMCMalaria Journal1475-28752018-11-0117111810.1186/s12936-018-2549-1Injectable anti-malarials revisited: discovery and development of new agents to protect against malariaFiona Macintyre0Hanu Ramachandruni1Jeremy N. Burrows2René Holm3Anna Thomas4Jörg J. Möhrle5Stephan Duparc6Rob Hooft van Huijsduijnen7Brian Greenwood8Winston E. Gutteridge9Timothy N. C. Wells10Wiweka Kaszubska11Medicines for Malaria VentureMedicines for Malaria VentureMedicines for Malaria VentureDrug Product Development, Janssen R&D, Johnson & JohnsonMedicines for Malaria VentureMedicines for Malaria VentureMedicines for Malaria VentureMedicines for Malaria VentureFaculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical MedicineMedicines for Malaria VentureMedicines for Malaria VentureMedicines for Malaria VentureAbstract Over the last 15 years, the majority of malaria drug discovery and development efforts have focused on new molecules and regimens to treat patients with uncomplicated or severe disease. In addition, a number of new molecular scaffolds have been discovered which block the replication of the parasite in the liver, offering the possibility of new tools for oral prophylaxis or chemoprotection, potentially with once-weekly dosing. However, an intervention which requires less frequent administration than this would be a key tool for the control and elimination of malaria. Recent progress in HIV drug discovery has shown that small molecules can be formulated for injections as native molecules or pro-drugs which provide protection for at least 2 months. Advances in antibody engineering offer an alternative approach whereby a single injection could potentially provide protection for several months. Building on earlier profiles for uncomplicated and severe malaria, a target product profile is proposed here for an injectable medicine providing long-term protection from this disease. As with all of such profiles, factors such as efficacy, cost, safety and tolerability are key, but with the changing disease landscape in Africa, new clinical and regulatory approaches are required to develop prophylactic/chemoprotective medicines. An overall framework for these approaches is suggested here.http://link.springer.com/article/10.1186/s12936-018-2549-1MalariaPlasmodiumChemoprotectionProphylaxisLiver schizontIntra-muscular |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Fiona Macintyre Hanu Ramachandruni Jeremy N. Burrows René Holm Anna Thomas Jörg J. Möhrle Stephan Duparc Rob Hooft van Huijsduijnen Brian Greenwood Winston E. Gutteridge Timothy N. C. Wells Wiweka Kaszubska |
spellingShingle |
Fiona Macintyre Hanu Ramachandruni Jeremy N. Burrows René Holm Anna Thomas Jörg J. Möhrle Stephan Duparc Rob Hooft van Huijsduijnen Brian Greenwood Winston E. Gutteridge Timothy N. C. Wells Wiweka Kaszubska Injectable anti-malarials revisited: discovery and development of new agents to protect against malaria Malaria Journal Malaria Plasmodium Chemoprotection Prophylaxis Liver schizont Intra-muscular |
author_facet |
Fiona Macintyre Hanu Ramachandruni Jeremy N. Burrows René Holm Anna Thomas Jörg J. Möhrle Stephan Duparc Rob Hooft van Huijsduijnen Brian Greenwood Winston E. Gutteridge Timothy N. C. Wells Wiweka Kaszubska |
author_sort |
Fiona Macintyre |
title |
Injectable anti-malarials revisited: discovery and development of new agents to protect against malaria |
title_short |
Injectable anti-malarials revisited: discovery and development of new agents to protect against malaria |
title_full |
Injectable anti-malarials revisited: discovery and development of new agents to protect against malaria |
title_fullStr |
Injectable anti-malarials revisited: discovery and development of new agents to protect against malaria |
title_full_unstemmed |
Injectable anti-malarials revisited: discovery and development of new agents to protect against malaria |
title_sort |
injectable anti-malarials revisited: discovery and development of new agents to protect against malaria |
publisher |
BMC |
series |
Malaria Journal |
issn |
1475-2875 |
publishDate |
2018-11-01 |
description |
Abstract Over the last 15 years, the majority of malaria drug discovery and development efforts have focused on new molecules and regimens to treat patients with uncomplicated or severe disease. In addition, a number of new molecular scaffolds have been discovered which block the replication of the parasite in the liver, offering the possibility of new tools for oral prophylaxis or chemoprotection, potentially with once-weekly dosing. However, an intervention which requires less frequent administration than this would be a key tool for the control and elimination of malaria. Recent progress in HIV drug discovery has shown that small molecules can be formulated for injections as native molecules or pro-drugs which provide protection for at least 2 months. Advances in antibody engineering offer an alternative approach whereby a single injection could potentially provide protection for several months. Building on earlier profiles for uncomplicated and severe malaria, a target product profile is proposed here for an injectable medicine providing long-term protection from this disease. As with all of such profiles, factors such as efficacy, cost, safety and tolerability are key, but with the changing disease landscape in Africa, new clinical and regulatory approaches are required to develop prophylactic/chemoprotective medicines. An overall framework for these approaches is suggested here. |
topic |
Malaria Plasmodium Chemoprotection Prophylaxis Liver schizont Intra-muscular |
url |
http://link.springer.com/article/10.1186/s12936-018-2549-1 |
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