Abstract：
: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 impact on TARGT hEPO secretion. These promising results suggest that TARGTs could be utilized for targeted delivery of therapeutic proteins to the CNS.
journal_name
Int J Pharmjournal_title
International journal of pharmaceuticsauthors
Aronson JP,Katnani HA,Pomerantseva I,Shapir N,Tse H,Miari R,Goltsman H,Mwizerwa O,Neville CM,Neil GA,Eskandar EN,Sundback CAdoi
10.1016/j.ijpharm.2017.10.002subject
Has Abstractpub_date
2017-12-20 00:00:00pages
42-49issue
1-2eissn
0378-5173issn
1873-3476pii
S0378-5173(17)30952-3journal_volume
534pub_type
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