About Rodin

Mission

Rodin is harnessing the power of epigenetic regulation of neuronal function to treat diseases of the brain. We believe targeted epigenetic regulation by HDAC complex modulation can restore synaptic function, health and survival (aka synaptic resilience) in degenerative brain diseases.

 

 

 

Our Approach: Synaptic Resilience

Synaptic Resilience through epigenetics
Epigenetic processes, the mechanisms by which specialized proteins turn genes on and off, play a critical role in learning and memory. Specifically, a chemical modification - histone acetylation (promoted by histone acetyltransferases, or HATs) - turns on (upregulates) genes important to brain cell function and stimulates the connections between neurons, called synapses. When this acetylation is reversed (de-acetylation) by protein complexes containing histone deacetylases (HDACs), these genes critical to learning and memory are turned down (downregulated).

Synaptic Resilience

Drugs that block deacetylation of histones (histone deacetylase inhibitors or HDAC inhibitors) may afford an opportunity to improve brain function by upregulating synaptic genes, especially in the diseased brain. In preclinical models, augmentation of histone acetylation with pan-HDAC inhibitors enhances learning and neuronal function through increased expression of neuronal proteins critically needed for synaptic functioning.

The need for more tailored HDACi properties

Numerous pan-HDAC inhibitors are under development and five have been approved for the treatment of cancer. However, while pan-HDAC inhibitors have demonstrated preclinical efficacy in models of cognition, approved HDACs are not targeted to the brain and have class-typical dose limiting toxicities, which both make them unsuitable for chronic dosing and for neurological indications. Thus, there is a need to discover safer and better tolerated HDAC inhibitors, tailored for the long-term therapy of brain diseases.

This HDAC approach is Rodin’s core focus. Rodin compounds enter the brain and target specific HDAC complexes associated with efficacy. As a result, Rodin compounds show functional efficacy and reduced side effects in preclinical models when directly compared to existing HDAC inhibitors. They are predicted to provide a greater margin of a safety in humans.

The Need for a better Synaptic Function

Rodin is establishing a full platform of assays around our proprietary compounds ranging from in vitro and preclinical studies to translational and clinical plans moving forward.

Synaptic Resilience

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