Prion derived chronic wasting disease discovered in Europe

Chronic wasting disease (CWD) has been detected in free ranging reindeer in Norway during a routine test. CWD is a lethal, contagious, neurological disease in cervids caused by a prion protein, similar to creutzfeldt-jakob disease in humans and bovine spongiform encephalopathy (BSE) in cows that lead to the mad cow disease outbreak in the 1980’s and 90’s . CWD has been known to be present in populations of deer, elk and moose in Northern America and South Korea, however this is the first confirmed infection in Europe, as well as the first reported case of CWS in free ranging reindeer worldwide (it has been published that reindeer can contract CWD in a laboratory environment). CWD occurs when a naturally occurring protein adopts an altered conformation. Other healthy forms of the same protein are then able to be induced to also take on this misfolding when in contact with the unhealthy prion protein. These misfolded proteins aggregate in the brain creating plaques resulting in weight loss, problems with co-ordination and behavioural changes. There is currently no successful treatment, and diagnosis is only possible through acquisition of brain tissue. Sylvie Benestad, an animal-disease researcher at the Norwegian Veterinary Institute in Oslo who, along with colleague Turid Vikøren, diagnosed the diseased reindeer stated she was “very afraid”, and allegedly expects that the disease has arisen spontaneously as opposed to have being imported from an infected area. There is also the possibility that the disease has broken the species barrier and scrapie from sheep has been transferred to reindeer, however such a jump has not been seen in prion disease before.

Prions from microscope. Photo: Sylvie Lafond Benestad, Norwegian Veterinary Institute.

Crispr crop gets green light

The first Crispr derived crop has been given a clear path to market by the US department of agriculture. The USDA has publicly stated that a mushroom variety genetically modified using the newest molecular biology superstar Crispr-Cas9 gene editing tool will not be subject to strict GM regulations. The common white button mushroom has been modified to resist browning by knocking out six of the polyphenol oxidase (PPO) genes that encode the enzyme responsible for mushroom browning. The experiments were carried out by Yinong Yang at Pennsylvania state university. Yang’s mushroom was not deemed necessary for regulation because it does not contain foreign DNA from ‘plant pests’ such as viruses or bacteria. The mushroom may still need to be assessed by the US food and drug administration (USFDA) and deemed safe for human consumption. The US is currently reviewing its regulatory processes and requirements for genetically modified organisms and the US National Academies of Sciences, Engineering and Medicine have instigated a committee charged with predicting potential advances in biotechnology products over the next 5–10 years. Their findings could be used to rewrite the GMO rule book, known as the coordinated framework for regulation of biotechnology.

Pain reaction recreated in iPSC derived neurons

Edward Stevens and James Blisland of the Pfizer’s U.K.-based neuroscience and pain research units have used induced pluripotent stem cells (iPSCs) derived from blood samples of patients to create sensory neurons. Fantastic in itself, however these particular iPSCs were taken from patients with a pain disorder and Stevens and Bilsland found that these particular neurons actually displayed the disease phenotype of the patient. The samples came from four patients with inherited erythromelalgia (IEM)—a vascular peripheral pain disorder. The patients were enrolled in a clinical trial for a pain drug that inhibits the periphery neuron-expressed Nav1.7 sodium channel, which transmits pain sensations. Some patients with IEM have mutations in the gene encode the channel making the individuals hypersensitive to heat pain and experience episodes of extreme burning pain triggered by heat, exercise, or other stimuli. The researchers developed iPSCs from erythroid progenitor cells and then selected the cells that displayed the corresponding mutation to the donating patients. These cells were then subjected to treatment by Nav1.7 inhibitor or moderate heat. The neurons from the patients with IEM were inhibited from spontaneous firing by Nav1.7 and were more sensitive to moderate heat than those from control patients. The study was from a small cohort, however Professor Paul Knoepfler, a stem cell researcher at the University of California stated that “while the physiological responses of the neurons from the four patients may not actually literally be ‘pain,’ they nonetheless may represent a useful surrogate assay for studying drugs that could alleviate pain in patients”. The use of cells from patient derived iPSCs in drug development trials could be quite a powerful tool, especially in cases of genetic mutations.

Written by: Brooke Lumicisi