Coda biotherapeutics series#

The Epilepsy Foundation estimates that one-third of people with epilepsy live with uncontrollable seizures because no available treatments are effective.Īccording to a study published in the Journal of Pain Research, 10 percent of the U.S. Patients suffer from stigmatization, social isolation, combined with disability, educational underachievement, and poor employment outcomes. According to the World Health Organization, recurrent seizures disrupt normal brain functions, lead to neuronal loss, and result in cognitive and emotional deficits. Focal epilepsy represents approximately 60 percent of all epilepsy (National Institute of Neurological Disorders and Strokes). Epilepsy is characterized by unpredictable seizures and the term 'focal' epilepsy is used to describe seizures that initiate from a specific location in the brain, typically in one hemisphere. Further assessment of the two selected cassettes, one driven by the pan-neuronal hSyn promoter and the other by CaMKII promoter, will be performed in an animal model of focal epilepsy to finalize the development candidate.Ībstracts can be accessed via the conference website at įirst Applications of the CODA Platform: Focal Epilepsy and Chronic Neuropathic Pain Epilepsy is one of the most common chronic neurological diseases and, according to the Centers for Disease Control, affects more than 65 million people around the world of which 3.4 million are in the U.S. mRNA analysis using ddPCR and immunofluorescence for cellular tropism demonstrated high levels of expression from human versions of the Syn- and CaMKII-driven cassettes. CaMKII and Syn are both excitatory neuron-specific promoters.įinally, the highest expressing cassettes from round two were assessed in vivo in male Sprague Dawley rat hippocampi by AAV9-mediated directed injection. Analysis by ddPCR revealed high levels of LGIC mRNA expression from CaMKII- and Syn-driven cassettes, which were comparable to the strong, ubiquitous CAG promoter. For the second round of selection, nine expression cassettes chosen from the first round were packaged into AAV9 vectors and transduced in neonatal rat hippocampal mixed cultures. Analysis by Droplet Digital PCR (ddPCR) and ELISA showed varying levels of expression, with the highest observed in cassettes containing the cytomegalovirus (CMV) promoter followed by those with various tissue-specific promoters. Plasmids with inverted terminal repeats (ITRs) flanking the regulatory cassettes driving LGIC expression were transfected in SKNAS neuroblastoma cells, as well as HeLa cells to determine which cassettes were able to target the cells more efficiently and provide high levels of LGIC expression. The first round of selection was performed in vitro with 23 unique expression cassettes containing various combinations of regulatory elements including, enhancer, promoter, intron, 5' untranslated region, 3' untranslated region, and polyA tail. Washington Convention Center Presenter: Edward Yeh Title: Assessment of AAV Regulatory Cassettes with Optimal Hippocampal Neuron Expression for the Treatment of Focal Epilepsy Date: 5:30-6:30 PM ET Session: Neurological Diseases I Poster Board Number: M-158 Abstract Number: 277 Location: Hall D, Walter E. We look forward to advancing our assessment of these two selected cassettes in epilepsy models to inform the final decision of our development candidate in focal epilepsy.' This research details the analysis and selection process of AAV regulatory cassettes that should drive optimal expression of our LGIC for the treatment of focal epilepsy. Recurrent seizures can result in cognitive and emotional deficits, with current interventions offering limited efficacy and multiple side effects.

Michael Narachi, president and CEO of CODA, said, 'Focal epilepsy is a chronic, debilitating neurologic disorder that is characterized by unpredictable seizures initiated from a specific location in the brain and affects millions of people around the world.

Coda biotherapeutics series#

To create an effective gene delivery approach for focal epilepsy, the Company generated a series of AAV expression cassettes that could drive optimal expression of its LGIC in target cells of the hippocampus.

Oral administration of this small molecule ligand, which is designed to only interact with CODA's chimeric LGIC, can be finely tuned to control the aberrant activity of neurons and suppress seizures without adverse effects. (PRNewsfoto/CODA Biotherapeutics, Inc.) (PRNewswire)ĬODA's approach to treat focal epilepsy is adeno associated virus (AAV)-mediated delivery of a novel engineered ligand-gated ion channel (LGIC) that can subsequently respond to an exogenous ligand.