14 December 2018 - - US-based synaptopathies drug developer Rodin Therapeutics has initiated a Phase 1 clinical trial of the company's lead candidate, RDN-929, a potent and selective HDAC-CoREST inhibitor, the company said.

The compound is designed to treat synaptopathies, a group of over 100 brain diseases characterized by synaptic loss and dysfunction.

This randomised, double-blind, placebo-controlled study will assess the safety, tolerability, pharmacokinetic and pharmacodynamic profile of single ascending and multiple ascending doses of RDN-929 in healthy volunteers ranging from 18 to 80 years old.

Inhibition of the CoREST complex targeted by RDN-929 is expected to reactivate neuronal gene expression, strengthen synaptic function and promote creation of new synapses while minimizing adverse effects.

RDN-929 preclinical data show pro-synaptic effects and suggest a safety profile suitable for long-term dosing as a therapeutic for neurodegenerative and neuropsychiatric diseases.

Rodin is also sponsoring an ongoing, non-therapeutic clinical trial to assess the performance of a new PET ligand that enables measurement of synaptic density in the living brain.

Results from this PET study and the newly launched Phase 1 trial will help guide Rodin's planned clinical trials of RDN-929 in patients with Alzheimer's disease, Parkinson's disease, frontotemporal dementia and other synaptopathies.

Rodin's lead compound is a potent and selective inhibitor of the CoREST complex. In preclinical studies, RDN-929 has demonstrated strong pro-synaptic pharmacological effects at multiple levels, including increase in the synaptic protein SV2A; significant, dose-dependent increase in dendritic spine morphology; and greater strength of synaptic function.

Rodin Therapeutics is discovering and developing first-in-class therapeutics for synaptopathies by applying novel chemical strategies to target specific HDAC complexes and upregulate key neuronal genes.

The company's targeted approach to strengthening synaptic integrity, backed by a robust translational strategy, has potential across multiple diseases, such as Alzheimer's disease, Parkinson's disease, frontotemporal dementia and schizophrenia, all of which are characterised by impaired neuronal and synaptic function.