Our Focus
Breakthrough science
A new approach to neurology therapies
Improving patient outcomes requires innovation.
Up to 40% of patients receiving current therapies for epilepsy and other neurological disorders fail to respond to treatment. Given this high unmet need we leveraged our patented machine-learning drug discovery platform to identify previously unexplored therapeutic targets for neurological conditions. Upon target identification our world class medicinal chemists rationally designed and validated first-in class small molecule compounds toward these targets.
The future of neurological therapeutics is inside the cell.
Most conventional neurological therapies target proteins outside the cell. Stream Neuroscience’s powerful new therapies delve deep inside the cell to activate crucial signalling molecules, allowing for regulation of several biological pathways responsible for neurological disease and brain health.
Stream Neuroscience’s lead program focuses on restoration of health in brain cells by increasing the amount of a signalling molecule called cyclic adenosine monophosphate (cAMP). In certain circumstances, adenosine triphosphate (ATP) is converted to cAMP, and cAMP activates many pathways important for brain health including signalling, growth, nourishment and anti-inflammation. Phosphodiesterase 4 (PDE4) is a protein that clears cAMP from the cell and restricts its influence. Stream Neuroscience’s novel treatments are Phosphodiesterase 4 inhibitors (PDE4i) and they reduce the activity of PDE4, leading to increased cAMP levels and restoration of key brain processes important for epileptic seizures and cognition.
How is Stream Neuroscience’s approach to phosphodiesterase 4 (PDE4) inhibition different?
PDE4 inhibitors (PDE4i) are approved for treatment of chronic obstructive pulmonary disorder (COPD), atopic dermatitis, psoriasis and psoriatic arthritis. PDE4is have been trialed in neurological diseases, although side effects prevented further development. Stream Neuroscience’s treatments target PDE4B, a specific type (isoform) of PDE4, and bind to a distinct part of the PDE4B protein. This unique approach to PDE4i chemistry allows for achievement of drug levels to treat neurological disorders while minimizing side effects.
How can PDE4B be used to treat neurological disorders?
Epileptic seizures are caused by too much excitatory signalling from cells in the top part of the brain, and not enough inhibitory signalling from cells in the bottom part of the brain. Cognitive decline is caused by changes in signalling in the middle part of the brain responsible for memory, with later changes in the top part of the brain responsible for reasoning, speech and language. PDE4B is prevalent in these brain areas, and by increasing cAMP through PDE4B inhibition brain cells are restored to a healthy level of signalling, thereby reducing the frequency of seizures and supporting improved cognition.