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Rodin Therapeutics aims to boost brain connections

$27 million will help test HDAC2 inhibitors to improve synapse health in Alzheimer’s patients

by Ryan Cross
September 18, 2017

Credit: Rodin Therapeutics
A photo of Rosenberg
Credit: Rodin Therapeutics

With the goal of designing small molecules to bolster brain connections, Cambridge, Mass.-based Rodin Therapeutics has raised $27 million in series B funding. CEO Adam Rosenberg says the money will get the company through a Phase I clinical trial in Alzheimer’s patients, expected to begin next year.

Rodin was founded in 2013 to exploit the knowledge that a common epigenetic mechanism—a chemical modification to boost or reduce gene expression—can be used to treat cognitive disorders linked to damaged or destroyed synapses. Dramatic synapse loss is one hallmark of Alzheimer’s, which Rodin aims to treat by turning up gene expression for proteins essential for maintaining old synapses and forming new ones.

Synapse damage in autopsied brains of human patients and mouse models of Alzheimer’s is linked to elevated levels of an epigenetic-controlling enzyme called histone deacetylase (HDAC) 2. This enzyme removes acetyl groups, causing regions of DNA to compact and effectively turn off. By designing molecules to inhibit HDAC2, Rodin scientists hope to restore or enhance brain connections by keeping genes important for synapse health turned on.

Some FDA-approved HDAC inhibitors exist as cancer therapies, but these drugs indiscriminately block many versions of HDAC. “Those are far too toxic for use in a neurological condition, and many of them don’t get into the brain,” Rosenberg says. The firm now has molecules that cross the blood-brain barrier and selectively block HDAC2, he adds.

A year ago, Rodin established a Chemical Advisory Board that meets bimonthly and has expedited the push toward a lead candidate drug, which Rosenberg says he “expects to nominate very soon.” Although seed-funder Johnson & Johnson and previous funder Biogen are not in the latest financing round, it does include returning investor Atlas Ventures, along with GV (formerly Google Ventures), Hatteras Venture Partners, Remeditex Ventures, and Third Point Ventures.

Rosenberg anticipates the firm’s compounds will have applications in other conditions characterized by synapse loss, including post-traumatic stress disorder, traumatic brain injury, schizophrenia, Rett Syndrome, frontotemporal dementia, and Huntington’s disease. “Our strategy is disease-area agnostic,” he says.



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