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Dried Blood Spot Collection of Health Biomarkers to Maximize Participation in Population Studies
Published on: January 28, 2014
Biomarkers
Vijay Benade1, Anil Shinde1, Rajesh Kumar Badange1
1Suven Life Sciences Ltd, Hyderabad, Telangana, India.
Background:
SUVN-I6107 is a novel and selective muscarinic M1 Positive Allosteric Modulator (PAM) being developed for the treatment of dementia due to neurodegenerative disorders. In the current research, the pharmacological properties of SUVN-I6107 in various animal models of cognitive deficits were investigated.
Methods:
SUVN-I6107 was characterized using a calcium mobilization assay and the binding affinity towards the orthosteric M1 - M5 site was investigated to assess the selectivity. The effect of SUVN-I6107 on neuronal spike rate in coronal hippocampal slice electrophysiology was studied in agonist and PAM modes of testing. The pharmacokinetic properties of SUVN-I6107 were studied both in rodent and non-rodent species. The effect of SUVN-I6107 on MK-801 (antagonist of the NMDA receptor) induced memory deficits in rats using object recognition task (ORT) and delay-induced social memory deficits in rats using social recognition task (SRT) was studied. Furthermore, effects of SUVN-I6107 on neuronal markers like soluble amyloid precursor protein (sAPPα) and inositol 1 phosphate (IP-1) levels were studied in rats.
Results:
SUVN-I6107 showed allosteric potency at M1 receptor (EC50 of 355 nM) with improved neuronal firing, when tested in combination with EC20 of carbachol. SUVN-I6107 showed good oral bioavailability in rats, dogs, and monkeys. SUVN-I6107 was found to have brain penetration properties with adequate protein-free fraction. In a rat model, SUVN-I6107 has reversed the delay, scopolamine and MK-801 induced amnesias in ORT. SUVN-I6107 also significantly improved the memory in contextual fear conditioning task and SRT. Treatment with SUVN-I6107 produced significant increase in levels of cortical sAPPα and striatal IP-1 in rats.
Conclusions:
Results from the non-clinical studies suggest SUVN-I6107 may have memory enhancing property in various forms of dementias. SUVN-I6107 is currently being studied in a Phase-1 study (NCT06705088) to evaluate its safety, tolerability, pharmacokinetics, and pharmacodynamic effects after single and repeated administrations in healthy human subjects.
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