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160 Results for Collaborations
Collaborations
Artemisinin combination therapy (ACT) is the standard of care in treating uncomplicated malaria, while newer synthetic endoperoxides like artefenomel are being actively studied in clinical trials. Adam Renslo, in the Department of Pharmaceutical Chemistry at the University of California, San Francisco (UCSF), is exploring artefenomel-like trioxolane analogs bearing a novel substitution pattern that may deliver improved physiochemical properties. To assist the Renslo Lab in driving this program toward clinical candidate selection, Medicines for Malaria Venture (MMV) is supporting the Renslo Lab in assessing the solubility, lipophilicity, and metabolic stability of frontrunner compounds using appropriate in vitro ADME assays. The resulting data will be a key factor in the selection of the best analogs for further in vivo evaluation. Given the extent of work and progress in the endoperoxide area, new compounds will only be of interest if their pharmacokinetics and potency support very low single dose potential with no alteration of parasite clearance between sensitive and resistant parasites. These early studies will help to assess the Renslo Lab compounds against this high bar.
Dr. Audrey Odom John (Washington University in St. Louis) and Dr. Cynthia Dowd (The George Washington University) identified an antimalarial drug candidate with a novel, parasite-specific target. The investigators have explored various solutions to improve the compound’s pharmacokinetic properties, including administration in a patch formulation. BVGH coordinated a call between Dr. Odom John, Dr. Dowd, and a Pfizer scientist with expertise in transdermal drug delivery to help assess the feasibility of this approach for the compound.
A Pfizer scientist with expertise in transdermal drug delivery shared advice on the feasibility of a transdermal delivery for the investigators’ antimalarial drug candidate and helped suggest next steps for development.
In an effort to develop novel drugs against Chagas disease, Dr. Artur Cordeiro at the Brazilian Biosciences National Laboratory (LNBio) has identified chemical scaffolds that have shown activity against two promising targets and efficacy against the parasite’s intracellular form. In order to identify additional inhibitors or novel chemical scaffolds with activity against both Trypanosoma cruzi enzymes, Dr. Cordeiro will be working with Novartis as part of their Facilitated Access to Screening Technologies (FAST) Lab program to screen several of Novartis’ proprietary compounds against these two targets to identify tool compounds for structure-based drug discovery.
Leishmaniasis is endemic in nearly 100 countries worldwide, and with treatment failure a growing problem, there is an urgent need for development of novel first-line agents. Dr. Edmund Ekuadzi, co-manager of the Kwame Nkrumah University of Science and Technology (KNUST) Central Laboratory and former Novartis Next Generation Scientist Program fellow, is exploring the anti-leishmanial properties of Ghanaian plants used in traditional medicines. He will receive training in bioassay-guided fractionation of plant extracts through the Wellcome Centre for Anti-Infectives Research (WCAIR) program at the University of Dundee to advance his drug discovery programs.
University of Dundee will be providing expertise on fractionation and synthesis of small molecule compounds, as well as a bioassay for the fractionation of plant extracts. University of Dundee will be hosting Dr. Ekuadzi for a three-month fellowship, beginning in June.
Buruli ulcer is a debilitating and stigmatizing disease, and affects mainly children in West and Central Africa. It is a chronic condition that results in skin lesions and can lead to permanent disability and disfigurement. Dr. Tianyu Zhang, Principal Investigator and Director of the National Key Laboratory for Respiratory Diseases at Guangzhou Institutes of Biomedicine and Health (GIBH), is exploring the bactericidal activity of the antibiotic candidate TB47 against Buruli ulcer. He will send the TB47 candidate to Professor Fabrice Boyom at the University of Yaoundé I for further testing against clinical Mycobacterium ulcerans strains.
GSK will be sharing its Tres Cantos Anti-Malarial Set (TCAMS) compound library with Drs. Audrey Odom John and Paul Hruz at WUSTL for screening for antimalarial drug discovery. TCAMS, developed as a component of GSK’s research at its Tres Cantos facility, is a diverse set of over 13,500 compounds with activity against blood-stage Plasmodium falciparum, plus associated screening data. GSK shares the TCAMS compounds and data widely to drive antimalarial drug discovery.
172 Results for Assets
Assets
The invention pertains to full-length polypeptides and fragments from naturally occurring Merozoite Surface Protein 1 (MSP-1; a protein expressed in later stage erythrocytic malaria) including vectors having encoding nucleic acids thereof that are useful as DNA vaccines. The intent was that the MSP-1 proteins expressed through these vectors would generate protective immune responses against subsequent infection by Plasmodium falciparum, the pathogen responsible for malaria.
Synthetic genes for malarial proteins and methods of use Synthetic gene sequences encoding erythrocyte binding protein of a malaria pathogen for the expression of the erythrocyte binding protein. The codon composition of the synthetic gene sequences approximates the mammalian codon composition. The synthetic gene sequences are useful for incorporation into the DNA vaccine vectors, for the incorporation into various expression vectors for production of malaria proteins, or both. The synthetic genes may be modified to avoid post-translational modification of the encoded protein in hosts. Administration of the synthetic gene sequences, or the encoded protein, as an immunization agent is useful for induction of immunity against malaria, treatment of malaria, or both.
Compositions that inhibit the binding of Plasmodium falciparum to erythrocytes include a family of erythrocyte binding proteins EBPs. The EBPs are paralogues of the P. falciparum binding protein EBA-175. The present invention includes peptides of the paralogues that prevent the binding of P. falciparum. Antibodies specific for each paralogue that also prevent the binding of P. falciparum are included. Methods of the invention utilize the paralogues, antibodies thereof and peptide compositions for the diagnosis, prevention, and treatment of P. falciparum diseases such as malaria, as well as methods for the detection of P. falciparum in biological samples and culture media.
Wucheria bancrofti, the major causative organism of lymphatic filariasis, is a filarial nematode estimated to infect 120 million people worldwide. The World Health Organization has targeted this disease for eradication. Current technology fails to recognize prepatent infections so there is a strong need for this technology in eradication efforts. This immunologically based assay detects Wuchereria bancrofti infection with no cross reactivity with other closely related filariae.
NIH Internal Reference no E-006-1990/0-US-01; US Patent Application no 07/470,692; and E-006-1990/0-US-02; US Patent Application no 08/462,616 Chloroquine an approved drug and the most commonly used antimalarial agent and analogs such as primaquine have been shown to inhibit infectious HIV-1 production and thus its spread in infected individuals. Inhibition may occur via interference with the terminal glycosylation of the viral glycoproteins, which results in the production of noninfectious virus.
This application relates to immunogenic conjugates which elicit an immune response to Plasmodium proteins. This application claims conjugates that include at least one Plasmodium sexual stage surface protein covalently linked to at least one Plasmodium circumsporozoite protein (CSP) or an immunogenic portion of a CSP. Also claimed in the application are conjugates that include at least one sexual stage surface protein covalently linked to at least one immunogenic repeat derived from a Plasmodium CSP. The inventors' data shows that these conjugates also induced long-lasting antibody responses to each of their components, i.e. the vaccine candidates showed both transmission blocking activity and antibodies to the CSP (or portion thereof).