ABSTRACT
The high efficacy of mRNA COVID-19 vaccine encourages the wider application of mRNA therapeutics. Protein replacement therapy with mRNA therapeutics is a promising alternative DDS approach for administering trophic factor proteins in central nervous system disorders or enzyme replacement therapy in inherited enzyme deficient diseases. Although the concept to deliver the mRNA in vivo as a drug was demonstrated as early as 1990, mRNA instability hindered subsequent research development. The polymer-based carrier, polyplex nanomicelle, is a novel carrier for in vivo mRNA administration. Here, we introduce the researches of in vivo mRNA administration using the nanomicelle carrier to treat animal models, especially focusing on the central nervous system disorders including Alzheimer’s disease, spinal cord injury and ischemic brain disease. We discuss the advantages of mRNA therapeutics and the characteristics of diseases which are highly suitable for mRNA therapeutics. © 2022, Japan Society of Drug Delivery System. All rights reserved.
ABSTRACT
Background: Previous reports have documented ground-glass opacities (GGOs), followed by appearance of the crazy pavement pattern and consolidation as the typical findings on chest computed tomography (CT) in patients with Coronavirus Disease-2019 (COVID-19). Case: A 69-year-old man with chronic renal failure and diabetes mellitus presented with a 2-day history of fever and fatigue, without cough or sputum production. Chest auscultation revealed coarse crackles at the right base. Laboratory findings included a normal leukocyte count, normal serum procalcitonin level, and a slightly elevated serum C-reactive protein level. Chest CT performed on day 2 after symptom onset revealed consolidation in the right lower lobe with an air bronchogram. The patient was tentatively diagnosed as having bacterial pneumonia, however, antibiotic treatment with ampicillin/sulbactam yielded no improvement of the symptoms, respiratory status, or laboratory findings. A repeat chest CT revealed changes in the findings of the right lower lobe from areas of focal consolidation to GGOs. GGOs and areas of consolidation were also detected in the other lung lobes. A polymerase chain reaction test for Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) returned a positive result. Discussion: Focal areas of lung consolidation is an atypical radiological presentation of coronavirus pneumonia. It is possible that the initial findings of CT represented those of bacterial pneumonia which responded to the antibiotic therapy, and that the GGOs that developed subsequently reflected new-onset SARS-CoV-2 pneumonia. However, the symptom of fatigue without cough or sputum, a normal leukocyte count, and a poor response to antibiotics are not typical findings of bacterial pneumonia. Our experience suggests that it is important to consider other or concomitant diseases when the initial treatment is followed by a deteriorating clinical course in patients with pneumonia. Moreover, it is essential to prevent the spread of hospital-acquired infection, especially if epidemic diseases need to be included in the initial differential diagnosis.