BRAIN Initiative: Development of Novel Tools to Probe Cell-Specific and Circuit-Specific Processes in Human and Non-Human Primate Brain (UG3/UH3 Clinical Trial Optional)
Funding Opportunity RFA-MH-19-135 from the NIH Guide for Grants and Contracts. The purpose of this Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative is to encourage applications that will develop and validate novel tools to facilitate the detailed analysis and manipulation of complex circuits and provide insights into cellular interactions that underlie brain function. Critical advances in the treatment of brain disorders in human populations are hindered by our lack of ability to monitor and manipulate circuitry in safe, minimally-invasive ways. Clinical intervention with novel cell and circuit specific tools will require extensive focused research designed to remove barriers to delivery of gene therapies. In addition to identification and removal of barriers, the need to specifically target dysfunctional circuitry poses additional challenges. Neuroscience has experienced an impressive influx of exciting new research tools in the past decade, especially since the launch of the BRAIN Initiative. However, the majority of these cutting edge tools have been developed for use in model organisms, primarily rodents, fish and flies. These cutting edge tools, such as viral delivery of genetic constructs, are increasingly adaptable to large brains and more importantly are emerging as potential human therapeutic strategies for brain disorders. A pressing need to develop tools for use in large brains, more directly relevant to the human brain is the focus...
Researchers are devising ways to prevent viral vectors carrying gene therapies from triggering an immune response
In conclusion, we show here that sEVs are responsible for mediating paracrine senescence and speculate that they could be involved in inducing bystander senescence during therapy-induced senescence or aging. In fact, when compared to soluble factors, sEVs have different biophysical and biochemical properties as they have a longer lifespan than do soluble factors and they are more resistant to protease degradation. The idea that blocking sEV secretion could be a potential therapeutic approach to alleviate senescence "spreading" during chemotherapy-induced senescence or in aging tissues presents itself as a very at...
Cancer Gene Therapy, Published online: 15 July 2019; doi:10.1038/s41417-019-0118-6MicroRNA-4268 inhibits cell proliferation via AKT/JNK signalling pathways by targeting Rab6B in human gastric cancer
Publication date: July 2019Source: Cytotherapy, Volume 21, Issue 7Author(s): Donald G. Phinney
Publication date: Available online 12 July 2019Source: The Lancet NeurologyAuthor(s): Marjo S van der Knaap, Raphael Schiffmann, Fanny Mochel, Nicole I WolfSummaryLeukodystrophies comprise a large group of rare genetic disorders primarily affecting CNS white matter. Historically, the diagnostic process was slow and patient prognosis regarded as poor because curative treatment was only available for very few leukodystrophies in early stages of the disease. Whole-exome sequencing has both greatly increased the number of known leukodystrophies and improved diagnosis. Whether MRI keeps its central place in diagnosis and what t...
Gene therapy has been employed in the human brain for a number of disorders in clinical trials and may serve as an avenue for the treatment of Parkinson's disease (PD). Several gene therapy treatment strategies have been developed and evaluated in patients with PD. Three main strategies have been used-enhancement of dopamine synthesis, expression of trophic factors, and neuromodulation. Typically, genes are delivered via viral vectors and expressed within neurons in PD-relevant areas of the brain such as the striatum.
Conclusion: Based on our presented case and a vast amount of literature there is circumstantial evidence that TCR gene therapy for melanoma targets the perivascular macrophage-like melanocytes in the stria vascularis, resulting in SNHL. We suggest that SNHL after TCR gene therapy may be caused by a disruption of the blood–labyrinth–barrier and the endolymphatic potential and/or a sterile inflammation of the stria vascularis. In severe cases like our subject, we posit that endolymphatic hydrops or hair cell loss may cause irreversible and asymmetrical deafness. Steroid prophylaxis via transtympanic application is debatable.
Gene Therapy, Published online: 12 July 2019; doi:10.1038/s41434-019-0092-5Beyond cystic fibrosis transmembrane conductance regulator therapy: a perspective on gene therapy and small molecule treatment for cystic fibrosis
Gene Therapy, Published online: 12 July 2019; doi:10.1038/s41434-019-0095-2Inside out: optimization of lipid nanoparticle formulations for exterior complexation and in vivo delivery of saRNA
Gene Therapy, Published online: 12 July 2019; doi:10.1038/s41434-019-0093-4Gene therapy of hematological disorders: current challenges