Distinguishing patients with idiopathic epilepsy from solitary cysticercus granuloma epilepsy and biochemical phenotype assessment using a serum biomolecule profiling platform.

A major source of epilepsy is Neurocysticercosis (NCC), caused by Taenia solium infection. Solitary cysticercus granuloma (SCG), a sub-group of NCC induced epilepsy, is the most common form of NCC in India. Current diagnostic criteria for SCG epilepsy require brain imaging which may not be available in communities where the disease is endemic. Identification of serum changes and potential biomolecules that could distinguish SCG epilepsy from idiopathic generalized epilepsy (IE), without the initial need for imaging, could assist in disease identification, understanding, and treatment. The objective here was to investigate, using mass spectrometry (MS), sera biomolecule differences between patients with SCG epilepsy or IE to help distinguish these disorders based on physiological differences, to understand underlying phenotypes and mechanisms, and to lay ground work for future therapeutic and biomarker analyses. Sera were obtained from patients with SCG or IE (N = 29 each group). Serum mass peak profiling was performed with electrospray ionization (ESI) MS, and mass peak area means in the two groups were compared using leave one [serum sample] out cross validation (LOOCV). Serum LOOCV analysis identified significant differences between SCG and IE patient groups (p = 10-20), which became non-significant (p = 0.074) when the samples were randomly allocated to the groups and reanalyzed. Tandem MS/MS peptide analysis of serum mass peaks from SCG or IE patients was performed to help identify potential peptide/protein biochemical and phenotypic changes involving these two forms of epilepsy. Bioinformatic analysis of these peptide/protein changes suggested neurological, inflammatory, seizure, blood brain barrier, cognition, ion channel, cell death, and behavior related biochemical systems were being altered in these disease states. This study provides groundwork for aiding in distinguishing SCG and IE patients in minimally invasive, lower-cost manners, for improving understanding of underlying epilepsy mechanisms, and for further identifying discriminatory biomarkers and potential therapeutic targets.

A scalable low-cost cGMP process for clinical grade production of the HIV inhibitor 5P12-RANTES in Pichia pastoris.

In the continued absence of an effective anti-HIV vaccine, approximately 2 million new HIV infections occur every year, with over 95% of these in developing countries. Calls have been made for the development of anti-HIV drugs that can be formulated for topical use to prevent HIV transmission during sexual intercourse. Because these drugs are principally destined for use in low-resource regions, achieving production costs that are as low as possible is an absolute requirement. 5P12-RANTES, an analog of the human chemokine protein RANTES/CCL5, is a highly potent HIV entry inhibitor which acts by achieving potent blockade of the principal HIV coreceptor, CCR5. Here we describe the development and optimization of a scalable low-cost production process for 5P12-RANTES based on expression in Pichia pastoris. At pilot (150 L) scale, this cGMP compliant process yielded 30 g of clinical grade 5P12-RANTES. As well as providing sufficient material for the first stage of clinical development, this process represents an important step towards achieving production of 5P12-RANTES at a cost and scale appropriate to meet needs for topical HIV prevention worldwide.

Economic implications of three strategies for the control of taeniasis.

OBJECTIVE: To evaluate the cost-effectiveness of three strategies for the control of taeniasis in a community, in terms of cost per case treated. METHODS: A study was conducted in South India to determine the prevalence of taeniasis by screening stool samples from 653 randomly chosen subjects, for coproantigens. The costs incurred in the project were used to estimate the cost per case screened and treated. A one-way sensitivity analysis was carried out for varying rates of taeniasis, different screening strategies and mass therapy. Further sensitivity analysis was carried out with different manpower and test costs. RESULTS: The rate of taeniasis as detected by ELISA for coproantigen was 3 per 1000 (2 of 653 samples). Our study showed that mass therapy without screening for taeniasis would be the most economical strategy in terms of cost per case treated if field workers are employed exclusively for either mass therapy or screening. For each strategy, costs per case treated are higher at low prevalence of taeniasis, with a sharp rise below 15%. CONCLUSIONS: In places that are endemic for taeniasis and neurocysticercosis, mass therapy or screening for taeniasis should be considered. Screening by stool microscopy is not cost-effective in terms of cost per case of taeniasis treated owing to its low sensitivity. Although the cost per case of taeniasis treated is high at low prevalence of taeniasis for all options, incorporating mass therapy into existing mass drug distribution programmes might prove to be the most cost-effective control strategy.