Ex-Vivo Gene Therapy Approach for Continuous Delivery of BDNF and Its Potential Use for Neurological Disorders (P02.013)
Bibliographic record
Abstract
Objective: Evaluating persistent delivery of BDNF by gene therapy. Background Brain-derived neurotrophic factor (BDNF) potently prevents neuronal death and stimulate neuronal function. BDNF gene delivery to the entorhinal cortex ameliorated neuronal death, improved hippocampus-dependent memory AD. Similarly it supports the survival of nigral dopaminergic neurons in Parkinson9s disease. BDNF is a neuroprotective agent when administered within hours of ischaemia, enhancing axonal sprouting and synaptic function. Unfortunately its use is hampered by short-half life, limited biodistribution and limited bioavailability. Thus, the ideal system for BDNF administration must achieve effective concentrations at sites of degenerating neurons and delivery must be sustained. Design/Methods: G8 primary mouse myoblasts were transfected with a plasmid containing the cDNA for human bdnf. In order to prevent allograft rejections, genetically engineered myoblasts expressing human BDNF cells were encapsulated within alginate-PLL microcapsules with a molecular cut-off size of 300KDa, thus permeable to bdnf (27KDa). C57BL/6 mice (n=3) were implanted intraperitoneally, each mouse with approximately 9 x 106 recombinant BDNF-secreting myoblasts. Levels of BDNF expression in vivo and in vitro were measured by ELISA. Clinical evaluation and histological analysis were performed to evaluate side effects. Results: Transgene expression of BDNF by engineered myoblasts was verified by ELISA. Engineered myoblasts produced human BDNF at a rate of 430pg/106 cells/day. Mice were bled on day 0, 3 and 7. There were low but detectable levels of bdnf in plasma of treated mice suggesting its persistent bioavailability BDNF is known to cross the blood-brain barrier. Histopathological analysis disclosed no side effects. Conclusions: The remarkable potency of growth factors in preventing cell death and stimulating cell function in CNS disease provides incentive for this research. Encapsulated recombinant myoblast expressing BDNF overcome problems of dosing, administration and sustained bioavailability that might have a substantial impact in neurological diseases. This therapeutic approach will be evaluated in degenerative conditions like AD. Disclosure: Dr. Gomez-Vargas has nothing to disclose. Dr. Hortelano has nothing to disclose. Dr. Rathbone has received research support from Sanofi-Aventis.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".