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154 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.
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.
172 Results for Assets
Assets
The class of compounds known as korupensamines exhibit in vitro and in vivo antimalarial activity and offer a potent new means for treating and controlling this devastating disease. As many as 2-3 million people worldwide die from malaria each year, and many more suffer from long-term chronic infection. The deadliest malarial parasites have become resistant to previously effective antimalarial drugs such as chloroquine and other clinically useful agents; therefore, effective new antimalarial drugs are urgently needed. These korupensamine compounds, which are isolated from a new species of the plant genus Ancistrocladus which is found in tropical Africa and southern and southeast Asia, effectively inhibit the growth, reproduction, and pathologic effects of a broad spectrum of Plasmodia parasites when given alone or in conjunction with previously available antimalarial agents. Licensees of this invention will be required to comport with all applicable federal and country-of-collection policies relating to biodiversity.
The invention provides a synthetic gene encoding an allelic fonn of non-glycosylat~d Plasmodium falciparum Apical Membrane Antigen 1 optimized for codon usage in Pichia pastoris (e.g., AMAI FVa and AMAI 3D7); the subsequent transfonnation of Pichia pastoris with this gene, the separate optimization for pH, temperature, growth rate, and media composition of reproducible, scalable, clinical grade fennentation conditions for the expressionof the products of the gene; a method of purification for de-lipidation to clinical grade purity of the products of the gene; and proof of efficacy of the purified protein products in in vitro growth inhibition assays and in vivo non-human primate challenge models.
Expression, Purification And Efficacy testing of Synthetic Plasmodium Falciparum Apical Membrane Antigen 1 Expressed in Pichia Pastoris Two recombinant forms of the malaria asexual blood stage antigen Apical Membrane Antigen 1 AMA1 were produced in Pichia pastoris using totally defined, synthetic medias and a fermentation methodology that has been reproducibly scaled over a 10-fold range to 60L. High levels of secreted recombinant protein were obtained 300mg/L secreted protein in the supernatant, and >50mg/L final purified bulk protein , and a purification strategy developed to remove Host cell-derived lipids. Highly purified forms of both types of AMA1 produced appear to produce antibodies in vivo in rabbits that block homologous parasites from invading red blood cells in vitro. The combination of the two allelic forms made appears potent at inducing antibodies capable of blocking the invasion of many heterologous parasite strains in vitro, suggesting that the combination of these two alleles of AMA1 will provide sufficient coverage from the diverse field populations of parasites. One of the two AMA1's, based on the FVO allelic variant of AMA1, was emulsified with complete and incomplete Freund's adjuvant. Vaccination of highly susceptible Aotus vociferansmonkeys with this formulation conferred significant protection from a subsequent lethal challenge with the virulent FVO Plasmodium falciparumparasite. Five of eight animals whose primary immune response was directed against AMA1 were completely protected. These two recombinant forms of AMA1 may be an effective malaria vaccine. The production and purification methodologies may be suitable to other therapeutic proteins where large-scale, inexpensive production methodologies are required.
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.