As a result of the significant disruption that is being caused by the COVID-19 pandemic we are very aware that many researchers will have difficulty in meeting the timelines associated with our peer review process during normal times.  Please do let us know if you need additional time. Our systems will continue to remind you of the original timelines but we intend to be highly flexible at this time.

In this Inspirational Note, Drs. Lara Milane and Mansoor Amiji share their insights and reflections on the impact of the recently approved SARS-CoV-2 mRNA vaccines on the present and future of translational nanomedicines.

Congratulations to the authors of Translational studies of intravenous and intracerebroventricular routes of administration for CNS cellular biodistribution for BMN 250, an enzyme replacement therapy for the treatment of Sanfilippo type B for winning the DDTR Best Paper of the Year Award for 2020.

Summary: Treatment of the neurological manifestations of lysosomal storage diseases remains an unmet medical need. BMN 250 is being developed as an enzyme replacement therapy administered directly into the brain ventricles via the intracerebroventricular (ICV) route for treating Sanfilippo type B.  Patients with this rare neurological disease have deficient lysosomal alpha-N-acetylglucosaminidase (NAGLU) enzyme activity. Unlike the ICV route that readily provides biodistribution of therapy to target cells, we show in wild-type and disease animal models that intravenously-administered enzyme does not reach the target neuronal cells. The limited pharmacological response following intravenous administration is likely attributed to the clearance of substrate in endothelial cells that restrict biodistribution to target cells in the brain. Representative staining from superficial medulla oblongata from cynomolgus monkey received BMN 250 via the IV route shows that all NAGLU staining is co-localized with CD31-positive endothelial cells, indicating that IV administered NAGLU does not reach the target neurons. In contrast, NAGLU co-localizes with the neurons following ICV administration.

In this Inspirational Note, Dr. Alexander Florence shares his reflections on the development of nanosystems designed for the delivery of biologically active agents.

This is an Open Access article and will be free to read in perpetuity.