Delayed viral vector mediated delivery of neurotrophin-3 improves skilled hindlimb function and stability after thoracic contusion

Sydney-Smith, Jared D.; Koltchev, Alice M.; Moon, Lawrence; Warren, Philippa M.

doi:10.1016/j.expneurol.2022.114278

Cited by 3 publications

(2 citation statements)

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“…However, contrary to the expectation that more practice/experience would enhance performance in the horizontal error ladder task, existing research has demonstrated that increased practice does not necessarily improve task pro ciency 43 . Moreover, results from a different study delivering NT-3 through gene therapy indicated a decrease in complete errors only after week 4, with statistical signi cance achieved only after 10 weeks, implying that our chosen time points may be too early to observe signi cant changes in this task 32 .…”

Section: Discussionmentioning

confidence: 95%

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Safe subdural administration and retention of a neurotrophin-3-delivering hydrogel in a rat model of spinal cord injury

Meissner,

Lopez,

Rees

et al. 2024

Preprint

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Neurotrophic growth factor (GF) loaded hydrogels have shown promise as a treatment approach for spinal cord injury (SCI). However, SCI presents complex challenges for the direct administration of treatment due to the spinal cord’s intricate anatomy and highly sensitive environment. Many current hydrogel administration approaches overlook this complexity, limiting their translational potential. To address this, we propose a novel intrathecal administration method using an in situ gelling, hyaluronic acid-modified heparin-poloxamer hydrogel loaded with neurotrophin-3 (NT-3) for the direct delivery of NT-3 to the spinal cord. We injected a NT-3 loaded hydrogel into the intrathecal space immediately after contusion SCI in Sprague Dawley (SD) rats. Our results indicate that injecting the NT-3 loaded hydrogel into the intrathecal space was safe and that the gel was retained alongside the cord for at least one week. Additionally, no adverse effects were observed on rat behaviour. While functional improvement trends were noted, statistical significance was not reached, and immunohistochemistry results showed no significant difference between treatment groups. Overall, our findings suggest the feasibility, safety, and potential of the developed intrathecal administration technique for delivering diverse therapeutic molecules for SCI recovery.

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Section: Discussionmentioning

confidence: 95%

“…2) and horizontal error ladder scores (Fig. 3) over a six-weeks period 21,22,32 . In terms of BBB scores, no signi cant differences were observed between the treatment groups at any time point (Fig.…”

Section: Evaluation Of Treatment E Cacymentioning

confidence: 99%