10 research outputs found
Gene and cell therapy in South Africa: Current status and future prospects
South Africa has a high disease burden resulting from communicable and non-communicable diseases. Current therapeutic interventions rarely result in a cure and the associated lifelong treatment places a considerable strain on an overburdened health sector. Gene and cell therapies present novel alternatives to disease management, offering the promise of a single treatment and a lifelong cure. Although challenges remain, investment in the field has started to bear fruit, with a number of gene and cell therapeutics reaching the market in the past decade. To take full advantage of these developments, it is important that a proactive approach to nurturing appropriate human and material resources is adopted in the country
Protecting participants in health research: The South African Material Transfer Agreement
The need to transfer human biological materials (HBMs) across national boundaries has become increasingly important in view of increased biobank and commercial activities globally. In light of South Africa (SA)’s history of colonisation and racial discrimination, coupled with well-known instances of exploitation of research participants in the developing world, it is critical that the management of HBMs from and to other jurisdictions is explored and regulated. Material transfer agreements (MTAs) represent an important point of departure in such a process. This article explores the need for a uniform MTA in SA and discusses some aspects of the recently gazetted national MTA, which provides a framework that can serve as a safeguard for cross-border transfer of HBMs in the absence of the National Health Act’s chapter 8 regulations in this regard
Protecting participants in health research: The South African Material Transfer Agreement
The need to transfer human biological materials (HBMs) across national boundaries has become increasingly important in view of increased biobank and commercial activities globally. In light of South Africa (SA)’s history of colonisation and racial discrimination, coupled with well-known instances of exploitation of research participants in the developing world, it is critical that the management of HBMs from and to other jurisdictions is explored and regulated. Material transfer agreements (MTAs) represent an important point of departure in such a process. This article explores the need for a uniform MTA in SA and discusses some aspects of the recently gazetted national MTA, which provides a framework that can serve as a safeguard for cross-border transfer of HBMs in the absence of the National Health Act’s chapter 8 regulations in this regard
Identification of 2,4-Disubstituted Imidazopyridines as Hemozoin Formation Inhibitors with Fast-Killing Kinetics and In Vivo Efficacy in the Plasmodium falciparum NSG Mouse Model
A series of 2,4-disubstituted imidazopyridines, originating from a SoftFocus Kinase library, was identified from a high throughput phenotypic screen against the human malaria parasite Plasmodium falciparum. Hit compounds showed moderate asexual blood stage activity. During lead optimization, several issues were flagged such as cross-resistance against the multidrug-resistant K1 strain, in vitro cytotoxicity, and cardiotoxicity and were addressed through structure–activity and structure–property relationship studies. Pharmacokinetic properties were assessed in mice for compounds showing desirable in vitro activity, a selectivity window over cytotoxicity, and microsomal metabolic stability. Frontrunner compound 37 showed good exposure in mice combined with good in vitro activity against the malaria parasite, which translated into in vivo efficacy in the P. falciparum NOD-scid IL-2Rγnull (NSG) mouse model. Preliminary mechanistic studies suggest inhibition of hemozoin formation as a contributing mode of action
Identification of 2,4-disubstituted imidazopyridines as hemozoin formation inhibitors with fast-killing kinetics and in vivo efficacy in the Plasmodium falciparum NSG mouse model
A series of 2,4-disubstituted imidazopyridines, originating from a SoftFocus Kinase library, was identified from a high throughput phenotypic screen against the human malaria parasite Plasmodium falciparum. Hit compounds showed moderate asexual blood stage activity. During lead optimization, several issues were flagged such as cross-resistance against the multidrug-resistant K1 strain, in vitro cytotoxicity, and cardiotoxicity and were addressed through structure-activity and structure-property relationship studies. Pharmacokinetic properties were assessed in mice for compounds showing desirable in vitro activity, a selectivity window over cytotoxicity, and microsomal metabolic stability. Frontrunner compound 37 showed good exposure in mice combined with good in vitro activity against the malaria parasite, which translated into in vivo efficacy in the P. falciparum NOD-scid IL-2Rgamma(null) (NSG) mouse model. Preliminary mechanistic studies suggest inhibition of hemozoin formation as a contributing mode of action