Inactivation of chronic wasting disease prions using sodium hypochlorite.

Chronic wasting disease (CWD) is a fatal prion disease that can infect deer, elk and moose. CWD has now been detected in 26 states of the USA, 3 Canadian provinces, South Korea, Norway, Sweden and Finland. CWD continues to spread from endemic areas, and new foci of infections are frequently detected. As increasing numbers of cervids become infected, the likelihood for human exposure increases. To date, no cases of CWD infection in humans have been confirmed, but experience with the BSE zoonosis in the United Kingdom suggests exposure to CWD should be minimized. Specifically, hunters, meat processors and others in contact with tissues from potentially CWD-infected cervids need a practical method to decontaminate knives, saws and other equipment. Prions are notoriously difficult to inactivate, and most effective methods require chemicals or sterilization processes that are either dangerous, caustic, expensive or not readily available. Although corrosive, sodium hypochlorite (bleach) is widely available and affordable and has been shown to inactivate prion agents including those that cause scrapie, bovine spongiform encephalopathy and Creutzfeldt-Jakob disease. In the current study, we confirm that bleach is an effective disinfectant for CWD prions and establish minimum times and bleach concentrations to eliminate prion seeding activity from stainless steel and infected brain homogenate solutions. We found that a five-minute treatment with a 40% dilution of household bleach was effective at inactivating CWD seeding activity from stainless-steel wires and CWD-infected brain homogenates. However, bleach was not able to inactivate CWD seeding activity from solid tissues in our studies.

JMV2894, a novel growth hormone secretagogue, accelerates body mass recovery in an experimental model of cachexia.

Oncologic patients subjected to chemotherapy frequently present aphagia, malnutrition, and cachexia. The purpose of this study was to investigate whether selected growth hormone secretagogues including hexarelin, JMV2894 and JMV2951 could antagonize body weight loss and wasting induced by cisplatin administration in rats. The three growth hormone secretagogues behaved as full agonists of the growth hormone secretagogues receptor both in terms of ability to stimulate calcium mobilization in Chinese hamster ovary cells and stimulation of growth hormone release in neonatal rats. Adult rats were (i) treated with vehicle throughout (controls), or (ii) treated with cisplatin (days 1-3) and a growth hormone secretagogues or vehicle, (days 1-12). Body weight and food consumption were measured daily. Although all growth hormone secretagogues caused initial transient acute increases in food intake, the total amount of food eaten by controls and growth hormone secretagogues treated groups over the 12 experimental days was not significantly different. All groups pre-treated with cisplatin lost up to 5-10 % body weight in the first 4 days; they subsequently gained weight at a rate comparable with controls. Interestingly, rats which received JMV2894 demonstrated a faster gain in body weight than any other growth hormone secretagogues treated group and at the end of the protocol reached a weight similar to that of controls. JMV2894 did not stimulate perirenal and epididymal fat accumulation but reduced MuRF mRNA levels in skeletal muscles. In conclusion, our findings demonstrate that JMV2894 antagonizes cisplatin induced weight loss in rats and may prove useful in antagonizing cachexia associated with cancer and chemotherapy in humans.

Use of a 2-aminothiazole to Treat Chronic Wasting Disease in Transgenic Mice.

Treatment with the 2-aminothiazole IND24 extended the survival of mice infected with mouse-adapted scrapie but also resulted in the emergence of a drug-resistant prion strain. Here, we determined whether IND24 extended the survival of transgenic mice infected with prions that caused scrapie in sheep or prions that caused chronic wasting disease (CWD; hereafter "CWD prions") in deer, using 2 isolates for each disease. IND24 doubled the incubation times for mice infected with CWD prions but had no effect on the survival of those infected with scrapie prions. Biochemical, neuropathologic, and cell culture analyses were used to characterize prion strain properties following treatment, and results indicated that the CWD prions were not altered by IND24, regardless of survival extension. These results suggest that IND24 may be a viable candidate for treating CWD in infected captive cervid populations and raise questions about why some prion strains develop drug resistance whereas others do not.

Assessment of prospective preventive therapies for chronic wasting disease in mule deer.

We compared prion infection rates among mule deer (Odocoileus hemionus) receiving pentosan polysulfate, tannic acid, tetracycline HCl, or no treatment 14 days before to 14 days after (dpi) oral inoculation with tonsil tissue homogenate. All deer were infected, but the rapid disease course (230-603 dpi) suggested our challenge was overwhelming.