Methodology and effects of repeated intranasal delivery of DNSP-11 in awake Rhesus macaques.
Repeated intranasal delivery of DNSP-11 in awake Rhesus macaques showed no adverse effects and engaged the dopamine system, but the clinical relevance of these findings is unclear.
Where it sits
this study against the rest of the dnsp-11 (dopamine neuron stimulating peptide-11) corpusSummary and findings
This study evaluated the repeated intranasal delivery of the neuroactive peptide DNSP-11 in awake Rhesus macaques over 10 weeks. The focus was on assessing striatal target engagement, safety, and brain distribution. No adverse behavioral effects or weight loss were reported.
Abstract
<h4>Background</h4>To determine if the intranasal delivery of neuroactive compounds is a viable, long-term treatment strategy for progressive, chronic neurodegenerative disorders, such as Parkinson's disease (PD), intranasal methodologies in preclinical models comparable to humans are needed.<h4>New method</h4>We developed a methodology to evaluate the repeated intranasal delivery of neuroactive compounds on the non-human primate (NHP) brain, without the need for sedation. We evaluated the effects of the neuroactive peptide, DNSP-11 following repeated intranasal delivery and dose-escalation over the course of 10-weeks in Rhesus macaques. This approach allowed us to examine striatal target engagement, safety and tolerability, and brain distribution following a single <sup>125</sup>I-labeled DNSP-11 dose.<h4>Results</h4>Our initial data support that repeated intranasal delivery and dose-escalation of DNSP-11 resulted in bilateral, striatal target engagement based on neurochemical changes in dopamine (DA) metabolites-without observable, adverse behavioral effects or weight loss in NHPs. Furthermore, a <sup>125</sup>I-labeled DNSP-11 study illustrates diffuse rostral to caudal distribution in the brain including the striatum-our target region of interest.<h4>Comparison with existing methods</h4>The results of this study are compared to our experiments in normal and 6-OHDA lesioned rats, where DNSP-11 was repeatedly delivered intranasally using a micropipette with animals under light sedation.<h4>Conclusions</h4>The results from this proof-of-concept study support the utility of our repeated intranasal dosing methodology in awake Rhesus macaques, to evaluate the effects of neuroactive compounds on the NHP brain. Additionally, results indicate that DNSP-11 can be safely and effectively delivered intranasally in MPTP-treated NHPs, while engaging the DA system.
Background
The paper addresses the potential effects of DNSP-11, a peptide hypothesized to influence dopamine neuron activity, in a primate model. Prior research has indicated that intranasal delivery can affect brain function, but the specific effects of DNSP-11 had not been thoroughly explored in awake primates. This study aims to fill that gap and provide insights into the peptide's effects on dopamine-related processes.
Methods
The study utilized a repeated intranasal delivery methodology in awake Rhesus macaques, though the exact population characteristics, sample size (n), dosage, and duration of treatment were not specified in the abstract. Primary and secondary outcome measures were not reported.
Results
Not reported in abstract.
Interpretation
Without specific results or effect sizes reported, it is challenging to compare these findings to existing literature or assess their clinical relevance. The lack of detailed outcomes limits the ability to draw conclusions about the peptide's efficacy or safety in this model. The absence of clear data also raises questions about the robustness of the findings and their applicability to clinical practice.
Key findings
- Not reported in abstract.
Limitations
- Not reported in abstract.