South African Medical Research Council

Cape Town, South Africa

South African Medical Research Council

Cape Town, South Africa

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Novel compound is active across the entire parasite lifecycle and holds great promise as a single dose cure A new paper published today in the prestigious journal Science Translational Medicine describes the discovery and biological profiling of an exciting new anti-malarial clinical drug candidate, MMV390048, effective against resistant strains of the malaria parasite, and across the entire parasite lifecycle, with the potential to cure and protect in a single dose. The research was conducted by the University of Cape Town (UCT)'s Drug Discovery and Development Centre, H3D, and Medicines for Malaria Venture (MMV), in collaboration with a team of international researchers. The paper is the first full disclosure of data demonstrating the antimalarial promise of MMV390048 (also known as MMV048), a compound discovered by an international team led by Professor Kelly Chibale at UCT and MMV. "The ability of MMV048 to block all life cycle stages of the malaria parasite, offer protection against infection as well as potentially block transmission of the parasite from person to person suggests that this compound could contribute to the eradication of malaria, a disease that claims the lives of several hundred thousand people every year," said Professor Chibale, Founder and Director of H3D, founding Director of the South African Medical Research Council (SAMRC) Drug Discovery Research Unit at UCT, and senior author of the paper. In 2014, MMV048 became the first new antimalarial medicine to enter phase I human studies in Africa. Today, preparations are being made to begin phase IIa human trials on this promising compound as a single-dose cure. "This compound has enormous potential," said Dr David Reddy, MMV's CEO. "In addition to the exciting characteristics noted, it has the potential to be administered as a single dose, which could revolutionize the treatment of malaria. At MMV, we look forward to continuing our work in partnership with Professor Chibale and colleagues at UCT to pursue the development of this and future next-generation antimalarials." The project has benefited from sustained funding from MMV, the South African Technology Innovation Agency (TIA) and Strategic Health Innovation Partnerships (SHIP) unit of the SAMRC. MMV's support has also been critical in helping H3D build and reinforce their scientific networks of drug discoverers and understand the compound's role in blocking the transmission of the malaria parasite. Despite the positive impact of medication, indoor spraying with insecticides and the use of insecticide bed-nets, around 429,000 people died from malaria in 2015, mostly in Africa, according to the World Health Organisation's World Malaria Report. The paper said resistance to treatment regimens still posed a threat and highlighted the importance of developing treatments containing new chemical classes with different modes of action. Contacts: Professor Kelly Chibale, Drug Discovery and Development Centre (H3D), University of Cape Town via Saroja Naicker - saroja.naicker@uct.ac.za +27 21 6501433 (office) or Kim Cloete cloetek@yahoo.co.uk +27 82 4150736 (mobile) H3D is Africa's first integrated drug discovery and development centre. H3D was founded at the University of Cape Town in April 2011 and pioneers world-class drug discovery in Africa. The vision of H3D is to be the leading organisation for integrated drug discovery and development on the African continent. H3D strives to discover and develop innovative, life saving medicines through excellence in interdisciplinary, translational science. According to the World Health Organisation's World Malaria Report, there were 212 million new cases of malaria worldwide in 2015, with 90% of cases occurring in the WHO Africa region. In 2015, there were an estimated 429,000 malaria deaths worldwide, with 92% of these deaths occurring in Africa. Children under five are particularly susceptible to malaria illness, infection and death. In 2015, malaria killed an estimated 303,000 under-fives globally, including 292,000 children in the African region. Issued by Kim Cloete on behalf of H3D, University of Cape Town. +27 82 4150736; cloetek@yahoo.co.uk


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP-SICA | Phase: SPA.2010.3.2-03 | Award Amount: 585.48K | Year: 2011

In Africa today, malaria is understood to be both a disease of poverty and a cause of poverty. Nevertheless, malaria is a preventable and curable disease. According to the Abuja declaration, the goal is to halve malaria mortality in Africa by 2010. (WHO, 2008, Status Report on Malaria in the African region). This report also states that most of the African countries within the region are attempting universal access to malaria prevention and control in the at risk areas. Fundamental is the control and management of the vector. There is a need for accurate and effective monitoring and evaluation systems as a resource to inform decisions that will assist in achieving these goals. Partnership between and within countries are essential to assist with access to and sharing of resources. The primary objective of MALAREO is to develop technology and implement EO capacities within malaria vector control and management programs in southern Africa. To achieve this objective, knowledge exchange and capability will occur in two directions (EU <-> SA). By doing this, the project will contribute to the installation of an EO monitoring cell that will support the daily work of the national malaria control programs.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-SICA | Phase: KBBE-2007-2-5-05 | Award Amount: 7.37M | Year: 2009

MYCORED aims at developing strategic solutions to reduce contamination by mycotoxins of major concern in economically important food and feed chains. The following toxins and commodities are especially considered in the project: aflatoxins, trichothecenes, zearalenone, fumonisins in wheat/maize food and feed chains; ochratoxin A in the grape-wine and wheat chains; and aflatoxins in the dried fruit chain. Novel methodologies, efficient handling procedures and information, dissemination and educational strategies are considered in a context of multidisciplinary integration of know-how and technology to reduce mycotoxins exposure worldwide. Five work-packages (WPs) will develop novel solution driven strategies to reduce both pre-and post-harvest contamination in feed and food chains. They involve: i) optimization of plant resistance and fungicide use; ii) biocontrol to reduce toxigenic fungi in cropping systems, iii) predictive modelling and optimise logistics; iv) novel post-harvest and storage practices and v) application of new food processing technologies. Two horizontal WPs will develop enabling methodologies for i) advanced diagnostics and quantitative detection of toxigenic fungi and ii) rapid and multi-toxin detection of mycotoxins and relevant biomarkers. The project will significantly build on the outcome of several European projects (through most coordinators/partners of FP5 and FP6) on mycotoxins by supporting, stimulating and facilitating education and cooperation with countries having major mycotoxin concerns related to (international) trade and human health. The direct involvement of ICPC countries (Argentina, Egypt, Russia, South Africa, Turkey) and international organizations (CIMMYT,IITA) together with strong alliances with major research institutions in the USA (3 USDA Centers/5 Universities), Australia, Malaysia will strengthen the project through sharing experiences and resources from several past/ongoing mycotoxin projects in a global context.


Grant
Agency: European Commission | Branch: FP7 | Program: MC-IAPP | Phase: FP7-PEOPLE-2013-IAPP | Award Amount: 2.04M | Year: 2013

Contemporary research has underscored the need for increased pharmaco-vigilence around codeine dispensing as the most commonly consumed opiate worldwide. Codeine represents an interesting quandary in terms of its regulated status, with individuals varying in their metabolism of codeine, estimation of safe dosages, and abuse potential. Within user trajectories of codeine use, a variety of sub groups exist in the form of the elderly, youth, parents, recreational, problematic and opiate dependent drug users, and each with their own motives, patterns and outcomes for use. Increases in treatment uptakes relating to codeine dependency and concerns for appropriate design of treatment protocols have been recorded globally. There is a clear need for this unique collaboration to present data on codeine user profiles so as to inform the design of protective mechanisms in the pharmacy profession to track, monitor , support and refer codeine misusers. The research aims to quantify the extent of codeine use, misuse and dependence in three countries (Ireland, United Kingdom and South Africa), with focus on therapeutic and non therapeutic use, so as to create user profiles of use and abuse and capture individual user, pharmacy, medic and treatment provider perspectives. Data will be used to inform the design of pharmacy based brief interventions and customer monitoring systems, continuing staff training and management of appropriate treatment interventions. A mixed method approach will commence with a meta-analysis and systematic review of literature, which along with national pharmacist, medic and treatment provider surveying, will inform the design and implementation of sweep surveys of individuals purchasing OTC codeine in pharmacies, internet based codeine user focus groups targeting web based sales and use, and interviews with codeine users, mis-users and dependents in each country.


News Article | February 24, 2017
Site: www.eurekalert.org

Successful results of a University of Liverpool-led trial that utilised nanotechnology to improve drug therapies for HIV patients has been presented at the Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle, a leading annual conference of HIV research, clinical practice and progress. The healthy volunteer trial, conducted by the collaborative nanomedicine research programme led by Pharmacologist Professor Andrew Owen and Materials Chemist Professor Steve Rannard, and in collaboration with the St Stephen's AIDS Trust at the Chelsea & Westminster Hospital in London, examined the use of nanotechnology to improve the delivery of drugs to HIV patients. The results were from two trials which are the first to use orally dosed nanomedicine to enable HIV therapy optimisation. Nanotechnology is the manipulation of matter on an atomic, molecular, and supramolecular scale. Nanomedicine is the application of nanotechnology to the prevention and treatment of disease in the human body. By developing smaller pills that are better for patients and less expensive to manufacture, this evolving discipline has the potential to dramatically change medical science and is already having an impact in a number of clinically used therapies and diagnostics worldwide. Currently, the treatment of HIV requires daily oral dosing of HIV drugs, and chronic oral dosing has significant complications that arise from the high pill burden experienced by many patients across populations with varying conditions leading to non-adherence to therapies. Recent evaluation of HIV patient groups have shown a willingness to switch to nanomedicine alternatives if benefits can be shown. Research efforts by the Liverpool team have focused on the development of new oral therapies, using Solid Drug Nanoparticle (SDN) technology which can improve drug absorption into the body, reducing both the dose and the cost per dose and enabling existing healthcare budgets to treat more patients. The trial results confirmed the potential for a 50 percent dose reduction while maintaining therapeutic exposure, using a novel approach to formulation of two drugs: efavirenz (EFV) and, lopinavir (LPV). EFV is the current WHO-recommended preferred regimen, with 70% of adult patients on first-line taking an EFV-based HIV treatment regimen in low- and middle-income countries. The trial is connected to the University's ongoing work as part of the multinational consortium OPTIMIZE, a global partnership working to accelerate access to simpler, safer and more affordable HIV treatment. Funded by the U.S. Agency for International Development, OPTIMIZE is led by the Wits Reproductive Health & HIV Institute in Johannesburg, South Africa, and includes the interdisciplinary Liverpool team, Columbia University, Mylan Laboratories and the Medicines Patent Pool (MPP). OPTIMIZE is supported by key partners including UNITAID and the South African Medical Research Council (SAMRC). Benny Kottiri, USAID's Office of HIV/AIDS Research Division Chief, said: "The potential applications for HIV treatment are incredibly promising. By aligning efforts, these integrated investments offer the potential to reduce the doses required to control the HIV virus even further, resulting in real benefits globally. This would enable the costs of therapy to be reduced which is particularly beneficial for resource-limited countries where the burden of disease is highest." To watch the presentation please follow the link http://www. For more information about the Conference on Retroviruses and Opportunistic Infections please visit http://www. .


News Article | February 24, 2017
Site: www.nanotech-now.com

Home > Press > New nano approach could cut dose of leading HIV treatment in half Abstract: Successful results of a University of Liverpool-led trial that utilised nanotechnology to improve drug therapies for HIV patients has been presented at the Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle, a leading annual conference of HIV research, clinical practice and progress. The healthy volunteer trial, conducted by the collaborative nanomedicine research programme led by Pharmacologist Professor Andrew Owen and Materials Chemist Professor Steve Rannard, and in collaboration with the St Stephen's AIDS Trust at the Chelsea & Westminster Hospital in London, examined the use of nanotechnology to improve the delivery of drugs to HIV patients. The results were from two trials which are the first to use orally dosed nanomedicine to enable HIV therapy optimisation. Manipulation of matter Nanotechnology is the manipulation of matter on an atomic, molecular, and supramolecular scale. Nanomedicine is the application of nanotechnology to the prevention and treatment of disease in the human body. By developing smaller pills that are better for patients and less expensive to manufacture, this evolving discipline has the potential to dramatically change medical science and is already having an impact in a number of clinically used therapies and diagnostics worldwide. Currently, the treatment of HIV requires daily oral dosing of HIV drugs, and chronic oral dosing has significant complications that arise from the high pill burden experienced by many patients across populations with varying conditions leading to non-adherence to therapies. Developing new therapies Recent evaluation of HIV patient groups have shown a willingness to switch to nanomedicine alternatives if benefits can be shown. Research efforts by the Liverpool team have focused on the development of new oral therapies, using Solid Drug Nanoparticle (SDN) technology which can improve drug absorption into the body, reducing both the dose and the cost per dose and enabling existing healthcare budgets to treat more patients. The trial results confirmed the potential for a 50 percent dose reduction while maintaining therapeutic exposure, using a novel approach to formulation of two drugs: efavirenz (EFV) and, lopinavir (LPV). EFV is the current WHO-recommended preferred regimen, with 70% of adult patients on first-line taking an EFV-based HIV treatment regimen in low- and middle-income countries. The trial is connected to the University's ongoing work as part of the multinational consortium OPTIMIZE, a global partnership working to accelerate access to simpler, safer and more affordable HIV treatment. Funded by the U.S. Agency for International Development, OPTIMIZE is led by the Wits Reproductive Health & HIV Institute in Johannesburg, South Africa, and includes the interdisciplinary Liverpool team, Columbia University, Mylan Laboratories and the Medicines Patent Pool (MPP). OPTIMIZE is supported by key partners including UNITAID and the South African Medical Research Council (SAMRC). Potential applications Benny Kottiri, USAID's Office of HIV/AIDS Research Division Chief, said: "The potential applications for HIV treatment are incredibly promising. By aligning efforts, these integrated investments offer the potential to reduce the doses required to control the HIV virus even further, resulting in real benefits globally. This would enable the costs of therapy to be reduced which is particularly beneficial for resource-limited countries where the burden of disease is highest." For more information, please click If you have a comment, please us. Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP-SICA | Phase: HEALTH-2009-4.3.2-2 | Award Amount: 2.28M | Year: 2009

Access to Pharmaceuticals Equitable access to pharmaceuticals, particularly for developing countries is an essential human right. Various complex impediments hinder access, which is the subject of ongoing multidisciplinary studies. Intellectual Property and product development are two issues that can be used as tools to address the problem of access, particularly to make patented drugs more affordable and accessible. This proposal addresses three ways of accomplishing this. The first is how academic licensing practices under socially responsible stewardship can ensure that future drugs that have resulted from inventive activity in academia will be available at low cost with improved access in the future. Secondly we will research thoroughly how existing public-private or product-development partnerships are addressing the issue of altruistic development of drugs for relatively neglected populations with unmet health needs and the lessons they have for future drug development. Lastly it addresses the current state and future improvements in compulsory licensing legislative instruments to enable access through generic manufacture of patented drugs. The three routes to access have several significant aspects of overlap which provide for complementary approaches and solutions to access.


Patent
South African Medical Research Council and University of Cape Town | Date: 2013-01-04

A method of determining in a subject a predisposition to, or increased risk for, developing a tendon, ligament, or other soft tissue injury or pathology, the method comprising the step of screening the subject for the presence of at least one polymorphism in at least one gene selected from the group comprising: a) the collagen V gene COL5A1; wherein the COL5A1 gene is rs71746744, rs16399 and/or rs1134170 within the 3-untranslated region (UTR) of the alpha 1 chain of the COL5A1 gene; b) the MIR608 gene which encodes a miRNA which binds to a recognition sequence within the 3-UTR of the collagen V gene COL5A1; and c) the CASP8 gene; wherein the presence of the polymorphism is indicative of a predisposition to, or increased risk for, developing a musculoskeletal soft tissue injury in the subject.


Cerf M.E.,South African Medical Research Council
Frontiers in Endocrinology | Year: 2013

Beta cell dysfunction and insulin resistance are inherently complex with their interrelation for triggering the pathogenesis of diabetes also somewhat undefined. Both pathogenic states induce hyperglycemia and therefore increase insulin demand. Beta cell dysfunction results from inadequate glucose sensing to stimulate insulin secretion therefore elevated glucose concentrations prevail. Persistently elevated glucose concentrations above the physiological range result in the manifestation of hyperglycemia. With systemic insulin resistance, insulin signaling within glucose recipient tissues is defective therefore hyperglycemia perseveres. Beta cell dysfunction supersedes insulin resistance in inducing diabetes. Both pathological states influence each other and presumably synergistically exacerbate diabetes. Preserving beta cell function and insulin signaling in beta cells and insulin signaling in the glucose recipient tissues will maintain glucose homeostasis. © 2013 Cerf.


Grant
Agency: GTR | Branch: MRC | Program: | Phase: Research Grant | Award Amount: 898.78K | Year: 2015

Integrating mental health care into primary health care services could reduce the impact of both chronic communicable and non-communicable diseases (NCDs). Like many low- and middle-income countries (LMICs), South Africa (SA) faces the challenge of how to reduce the high prevalence and impact of communicable diseases and NCDs, including mental disorders where limited services are available. Mental disorders are important to address among patients with chronic diseases as these problems are associated with poor adherence to treatment, more rapid disease progression and treatment failure. As treatment failure increases the use of health services and health service costs, chronic disease care in LMICs must be expanded to include mental health care. The integrated delivery of mental health services and chronic disease care has been shown to not only improve access to mental health care but also the mental health of patients living with a chronic disease. . Yet, limited knowledge of how mental health care can be integrated into chronic disease services in ways that are acceptable to patients and providers and feasible to implement with few resources has delayed the integration of services in SA. The provision of integrated mental health and chronic disease services has also been delayed by questions about whether services should be vertically or horizontally integrated. Vertically integrated services are delivered at the same location, but mental health and chronic disease services are provided by separate cadres of health workers. Horizontally integrated services are delivered at the same location by the same staff are responsible for mental health and chronic disease care. The goal of this project is to answer these questions by assessing current capacity and barriers to integrating mental health services into chronic disease care and by comparing the effectiveness and cost-effectiveness of a vertically and horizontally integrated model of service integration among patients receiving treatment for HIV or diabetes and who are at risk for treatment failure in Cape Town, SA. Through this project we hope to identify a feasible, acceptable and effective model for integrating mental health services into chronic disease care that is applicable to other LMICs. Findings from this study are likely to be highly relevant for use in other LMICs given similarities between the burden of disease, treatment populations, and treatment systems in SA and other LMICs. The study will comprise two phases. In the first phase, we will conduct in-depth interviews with a range of healthcare providers in HIV and diabetes services to assess barriers to integration and the feasibility and acceptability of our proposed models of service integration (Aim 1). Findings from this phase will be used to adapt our evidence-based mental health service package for optimal integration into chronic disease services. In phase two, a clustered randomised controlled trial will be conducted. We will select 24 HIV and 24 diabetes clinics to randomise to a vertically integrated arm, horizontally integrated arm, or treatment as usual (no integration). We will recruit 25 patients at risk for treatment failure from each of these clinics (total 1200 patients). After study enrollment, a baseline assessment will be completed by a fieldworker. Participants recruited from clinics randomised to either the vertically integrated or horizontally integrated arm will then receive their intervention sessions. All participants, irrespective of their intervention arm, will be tracked for 6- and 12-month follow-up interviews. At these interviews, fieldworkers blinded to their intervention arm will re-administer the baseline assessment and biological specimens will be collected to assess for chronic disease outcomes. Findings from this phase will be used to evaluate the relative effectiveness and cost-effectiveness of our proposed models of service integration (Aims 2-3).

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