Designer receptors to modulate the activity of target cells

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CODA Biotherapeutics’ revolutionary chemogenetic platform aims to control the activity of cells to treat disease. With chemogenetics, the goal is to modify a target cell population using gene therapy to express a tunable “switch” protein. Cells modified with the “switch” can be activated or inactivated in a dose-dependent manner by a subsequently administered small molecule therapeutic, an effect that should only occur in the modified cells.

 

CODA’s engineered receptors will be able to modulate the activity of virtually any cell in which the receptor is ectopically expressed, making them suitable for the treatment of many disorders. CODA can further tailor the therapy to a particular disease by simply changing the viral capsid, DNA regulatory elements, and route of administration.

 

 

Orally controlled, locally targeted cellular modulation in three parts:

1: SWITCH

Minimally-modified human receptors, engineered to interact selectively with pharmacological agents

2: VECTOR

Proprietary viral vectors for delivering the gene encoding a switch receptor to enable targeted cellular control

3: LIGAND

Pharmacological agents, administered as needed to provide therapeutic benefit with minimal systemic effects

Applications


CODA’s first clinical application is directed to the management of chronic neuropathic pain  

CODA is developing engineered neurotransmitter receptors that are activated exclusively by orally bioavailable drugs to control the activity of hyperexcitable neurons responsible for chronic neuropathic pain. The gene encoding the receptor is delivered to dysfunctional neurons by proprietary viral vectors that are optimized for robust and targeted gene transfer. Standard neurosurgical procedures are used to administer these viral vectors directly to the neurons to be controlled. Once expressed, the engineered receptor can be activated by the drug to modulate neuronal activity. This enables the selective, tunable and reversible regulation of the receptor – and hence cellular activity – based on the dosing regimen of the drug. CODA is engineering receptors to have exquisite sensitivity for the pharmacological activator, which should dramatically limit off-target side effects that plague many pharmaceutical treatments.

 

More than 19 million Americans live with chronic neuropathic pain. 

Nearly 10 million Americans take opioids for long-term pain and 2.1 million are estimated by the National Institutes of Health to be addicted. Current pharmacological therapies such as opioids, anticonvulsants, tricyclic anti-depressants and channel inhibitors provide little relief while having significant side effects and a potential for addiction. Nerve stimulation therapies require batteries and wires that need maintenance and carry a risk of infections. Surgeries that destroy pathological neurons are a last resort and can have permanent adverse effects on peripheral nervous system function.

 

With CODA’s tunable gene therapy platform, pathological neural circuits can be controlled in a highly targeted, dose-dependent, reversible and durable manner. 

Some examples of chronic neuropathic pain that we believe will be treatable by the CODA approach include:

Avulsion/nerve injury

Cancer Pain

CRPS

Diabetic Neuropathy

Interstitial Cystitis

Osteoarthritis

Phantom Limb pain

Postherpetic Neuralgia

Radiculopathy

Spinal Cord injury

Trigeminal Neuralgia

Failed Back

Additional Neurological Applications


Addiction

ALS

Alzheimer’s disease

Anxiety

Atrial fibrillation

Autism

Dementia

Depression

Down Syndrome

Eating disorders

Epilepsy

GERD

Memory loss

Movement disorders

Narcolepsy

Parkinson’s disease

PTSD

Sleep Apnea

Spasticity disorders

Stroke

Bladder disorders