'A case of autoimmune hepatitis associated with the PCSK9 inhibitor alirocumab'.

This is a case of a 61-year-old lady who presented to the lipid clinic with possible familial hypercholesterolaemia (Simon Broome Criteria). She was commenced on atorvastatin; however, 4 weeks later, she developed hepatitis, and therefore her atorvastatin was discontinued. Following that, her liver function tests normalized, and she was diagnosed with statin-induced hepatitis. Three years later, she was seen again in the lipid clinic with an uncontrolled lipid profile, and she was commenced on alirocumab, a Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) inhibitor. A few days later, she developed hepatitis, and subsequently, the alirocumab was discontinued. She underwent a liver biopsy, which confirmed that she had Autoimmune Hepatitis (AIH) with presumed superimposed drug injury. This is the first reported case of autoimmune hepatitis associated with alirocumab.

The effect of Me2SO overexposure during cryopreservation on HOS TE85 and hMSC viability, growth and quality.

With the cell therapy industry continuing to grow, the ability to preserve clinical grade cells, including mesenchymal stem cells (MSCs), whilst retaining cell viability and function remains critical for the generation of off-the-shelf therapies. Cryopreservation of MSCs, using slow freezing, is an established process at lab scale. However, the cytotoxicity of cryoprotectants, like Me2SO, raises questions about the impact of prolonged cell exposure to cryoprotectant at temperatures >0 °C during processing of large cell batches for allogenic therapies prior to rapid cooling in a controlled rate freezer or in the clinic prior to administration. Here we show that exposure of human bone marrow derived MSCs to Me2SO for ≥1 h before freezing, or after thawing, degrades membrane integrity, short-term cell attachment efficiency and alters cell immunophenotype. After 2 h's exposure to Me2SO at 37 °C post-thaw, membrane integrity dropped to ∼70% and only ∼50% of cells retained the ability to adhere to tissue culture plastic. Furthermore, only 70% of the recovered MSCs retained an immunophenotype consistent with the ISCT minimal criteria after exposure. We also saw a similar loss of membrane integrity and attachment efficiency after exposing osteoblast (HOS TE85) cells to Me2SO before, and after, cryopreservation. Overall, these results show that freezing medium exposure is a critical determinant of product quality as process scale increases. Defining and reporting cell sensitivity to freezing medium exposure, both before and after cryopreservation, enables a fair judgement of how scalable a particular cryopreservation process can be, and consequently whether the therapy has commercial feasibility.

Expression of Aedes trypsin-modulating oostatic factor on the virion of TMV: A potential larvicide.

We report the engineering of the surface of the tobacco mosaic virus (TMV) virion with a mosquito decapeptide hormone, trypsin-modulating oostatic factor (TMOF). The TMV coat protein (CP) was fused to TMOF at the C terminus by using a read-through, leaky stop codon that facilitated expression of CP and chimeric CP-TMOF (20:1 ratio) that were coassembled into virus particles in infected Nicotiana tabacum. Plants that were infected with the hybrid TMV RNA accumulated TMOF to levels of 1.3% of total soluble protein. Infected tobacco leaf discs that were fed to Heliothis virescens fourth-instar larvae stunted their growth and inhibited trypsin and chymotrypsin activity in their midgut. Purified CP-TMOF virions fed to mosquito larvae stopped larval growth and caused death. Because TMV has a wide host range, expressing TMV-TMOF in plants can be used as a general method to protect them against agricultural insect pests and to control vector mosquitoes.