Sustained intrathecal therapeutic protein delivery using genetically transduced tissue implants in a freely moving rat model

Publication date: 20 December 2017 Source:International Journal of Pharmaceutics, Volume 534, Issues 1–2 Author(s): J.P. Aronson, H.A. Katnani, I. Pomerantseva, N. Shapir, H. Tse, R. Miari, H. Goltsman, O. Mwizerwa, C.M. Neville, G.A. Neil, E.N. Eskandar, C.A. Sundback Systemic delivery of therapeutic proteins to the central nervous system (CNS) is challenging because of the blood-brain barrier restrictions. Direct intrathecal delivery is possible but does not produce stable concentrations. We are proposing an alternative approach for localized delivery into the CNS based on the Transduced Autologous Restorative Gene Therapy (TARGT) system. This system was previously developed using a gene therapy approach with dermal tissue implants. Lewis rat dermal tissue was transduced to secrete human EPO (hEPO). TARGT viability and function were retained following cryopreservation. Upon implantation into the rat cisterna magna, a mild inflammatory response was observed at the TARGT-brain interface throughout 21-day implantation. hEPO expression was verified immunohistochemically and by secreted levels in cerebrospinal fluid (CSF), serum, and in vitro post explant. Detectable CSF hEPO levels were maintained during the study. Serum hEPO levels were similar to rat and human basal serum levels. In vitro, the highest hEPO concentration was observed on day 1 post-explant culture and then remained constant for over 21days. Prolonged incubation within the cisterna magna had no negative i...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research

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CONCLUSIONS: The applications of CRISPR technology are widely established in the diagnosis and treatment of various bacterial, viral, fungal and parasitic infectious diseases. CRISPR technology is a simple, efficient and tested on a broad range of microorganisms to rectify disease-associated genetic defects and destroy invading foreign DNA to human cells or tissues. PMID: 29917197 [PubMed - in process]
Source: European Review for Medical and Pharmacological Sciences - Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research
Rationale: Delivery of nucleic acid molecules into skin remains a main obstacle for various types of gene therapy or vaccine applications. Here we propose a novel electroporation approach via combined use of a microneedle roller and a flexible interdigitated electroporation array (FIEA) for efficient delivery of DNA and siRNA into mouse skin.Methods: Using micromachining technology, closely spaced gold electrodes were made on a pliable parylene substrate to form a patch-like electroporation array, which enabled close surface contact between the skin and electrodes. Pre-penetration of the skin with a microneedle roller resu...
Source: Theranostics - Category: Molecular Biology Authors: Tags: Research Paper Source Type: research
Molecular imaging has played an important role in the noninvasive exploration of multiple biological processes. Reporter gene imaging is a key part of molecular imaging. By combining with a reporter probe, a reporter protein can induce the accumulation of specific signals that are detectable by an imaging device to provide indirect information of reporter gene expression in living subjects. There are many types of reporter genes and each corresponding imaging technique has its own advantages and drawbacks. Fused reporter genes or single reporter genes with products detectable by multiple imaging modalities can compensate f...
Source: Theranostics - Category: Molecular Biology Authors: Tags: Review Source Type: research
Conclusion: We developed isogenic hSSTr2-expressing ESCs that allow noninvasive cell monitoring in the context of PSC-derived regenerative therapy. Furthermore, we are the first to use the hSSTr2 not only as an imaging reporter gene, but also as a suicide mechanism for radionuclide therapy in the setting of PSC-derived cell treatment.
Source: Theranostics - Category: Molecular Biology Authors: Tags: Research Paper Source Type: research
Conclusion: The above results indicated the gold nanoshell-based system would be a promising translational nano-formulation platform for effective treatment of EML4-ALK-positive NSCLC.
Source: Theranostics - Category: Molecular Biology Authors: Tags: Research Paper Source Type: research
AbstractAutism spectrum disorder (ASD) is characterised by the concomitant occurrence of impaired social interaction; restricted, perseverative and stereotypical behaviour; and abnormal communication skills. Recent epidemiological studies have reported a dramatic increase in the prevalence of ASD with as many as 1 in every 59 children being diagnosed with ASD. The fact that ASD appears to be principally genetically driven, and may be reversible postnatally, has raised the exciting possibility of using gene therapy as a disease-modifying treatment. Such therapies have already started to seriously impact on human disease and...
Source: Molecular Autism - Category: Molecular Biology Source Type: research
Big pharma companies need to buy innovation, biotech companies are getting sky-high valuations, and 2018 is shaping up to be the second biggest M&A year for the sector on record.
Source: Forbes.com Healthcare News - Category: Pharmaceuticals Authors: Tags: NASDAQ:SYNH NASDAQ:CELG NYSE:NVS Source Type: news
(Reuters) - Sarepta Therapeutics' shares jumped 60 percent on Tuesday after promising results from a gene therapy study positioned the specialty drugmaker as a potential leader in the market for Duchenne muscular dystrophy (DMD) treatments.
Source: Reuters: Health - Category: Consumer Health News Tags: healthNews Source Type: news
Sarepta Therapeutics on Tuesday released promising data from a small, early-stage trial of its experimental gene therapy treatment for Duchenne muscular dystrophy, showing that the drug significantly boosted an important muscle protein in three boys with the disease. Shares of Sarepta (Nasdaq: SRPT) soared Tuesday morning on the news, propelling its market cap from $6.9 billion to more than $11 billion briefly, before dropping back to $10.6 billion as of 11:15 a.m. The stock increase of 54 percent…
Source: bizjournals.com Health Care:Pharmaceuticals headlines - Category: Pharmaceuticals Authors: Source Type: news
(Reuters) - Sarepta Therapeutics Inc shares jumped 60 percent on Tuesday after the drugmaker reported promising results from an early-stage study testing its gene therapy in patients with Duchenne muscular dystrophy (DMD).
Source: Reuters: Health - Category: Consumer Health News Tags: healthNews Source Type: news
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