Breakthrough science
A new approach to neurology therapies
Improving patient outcomes requires innovation.
It is well known that disruptions to cell balance and bioenergetics result in abnormal communication between areas of the brain. These challenges in signaling between brain regions underlie most neurological disorders, including epilepsy, Alzheimer’s Disease, and depression. Given this shared etiology, Stream Neuroscience developed a patented machine-learning drug discovery platform called MitoREAD to identify novel protein targets deep within brain cells that can restore and maintain neural balance. Once a protein target is identified and experimentally validated, Stream Neuroscience’s world-class medicinal chemists initiate a traditional drug discovery pipeline to create first-in-class small molecule compounds to target these pathways. Stream Neuroscience’s discovery and development therapies have emerged from MitoREAD discoveries.
Why are cell bioenergetics important for a healthy brain?
Cells, like people, need energy to survive and thrive. Our bodies need to utilize energy efficiently to function at our best, and so do cells. Energy is supplied to cells by conversion of a molecule called Adenosine Triphosphate (ATP) to Adenosine Diphosphate (ADP) by energy-rich processes in the brain. In certain circumstances, ATP instead is converted directly to cyclic adenosine monophosphate (cAMP), and cAMP activates many pathways that are crucial for brain health including signalling, growth, nourishment and anti-inflammatory processes in neurons and neural support cells. Phosphodiesterases are proteins that clear cAMP from the cell and restricts its influence. Stream Neuroscience is developing novel treatments that reduces the activity of phosphodiesterases leading to increased cAMP levels and the restoration of key brain processes.
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 (PDE) inhibition different?
There are 11 identified PDE subtypes (PDE1, PDE2, … PDE11), which are used to treat conditions such as erectile dysfunction (PDE5), cardiovascular disease (PDE3), and asthma (non-specific PDE). PDE4 inhibition is already a common treatment for chronic obstructive pulmonary disorder (COPD) and psoriasis, and has been trialed in neurological diseases, although side effects prevented further development. Stream Neuroscience’s treatments target PDE4B, a specific type (isoform) of PDE4 that is prevalent in the brain, and binds to a distinct part of the PDE4B protein to achieve therapeutic levels while minimizing side effects.
How can PDE4B be used to treat neurological disorders?
By restoring and maintaining cell balance neurons and neural support cells can function at their best. Seizures in epilepsy, for example, are caused by too much excitatory signaling from neurons in the top part of the brain, and not enough inhibitory signaling from neurons in the bottom part of the brain. Cognitive decline, like in Alzheimer’s Disease, is thought to be caused by changes in neuron signaling in the middle part of the brain that are responsible for memory, with later changes in the top part of the brain, responsible for reasoning, speech and language. Stream Neuroscience’s PDE4B inhibitor treatments return neuron and neuronal support cells to a healthy level of signalling by restoring and maintaining cell energetic balance, thereby reducing the frequency of seizures and potentially improving cognition.