Introduction to CereSpir

CereSpir is targeting the emerging field of immuno-neurology via a novel mechanism for the treatment of Parkinson’s disease and other neurodegenerative diseases

CereSpir Incorporated is a privately held, biotechnology company with an innovative approach to treating neurodegenerative disorders. CereSpir is leading the way by focusing on a novel class of pharmacological agents known as AICD inhibitors. They act by preventing the destructive cycle of neuroinflammation and neurodegeneration which is initiated by chronic oxidative stress. Low levels of oxidative stress produced during normal metabolism,  are counterbalanced in neurons and glial cells (the immune cells of the brain)  by the production of antioxidant enzymes.  FoxO3a is a critically important component of the cell’s response to oxidative stress controlling the production of  antioxidant enzymes.  However, under conditions of chronic oxidative stress such as from the accumulation of alpha-synuclein in the brains of patients with Parkinson’s disease, both AICD and Fox03a levels are increased and AICD interacts with FoxO3a in the nucleus to cause cell death via apoptosis.  Parkinson’s disease is a common, progressive neurodegenerative disorder associated with loss of midbrain dopaminergic neurons which produce the essential neurotransmitter, dopamine.  LRRK2 is a protein kinase involved in intracellular protein trafficking and autophagy. LRRK2 gain of function mutants are responsible for the majority of cases of familial Parkinson’s disease.  Additionally, LRRK2 kinase activity is aberrantly increased in vulnerable dopamine neurons by oxidative mechanisms involving α-synuclein and mitochondrial impairment, suggesting LRRK2 inhibition will be effective for the treatment of the majority of Parkinson’s disease patients.    A group of internationally recognized  investigators at the National Neuroscience Institute Singapore led by Professor Eng King Tan recently discovered that AICD is phosphorylated and, thereby,  activated by LRRK2. The resulting loss of dopaminergic neurons in a LRRK2 transgenic model of Parkinson’s disease suggested that AICD inhibitors would have significant benefit in Parkinson’s disease.  CereSpir’s lead clinical stage compound itanapraced uniquely binds to AICD and inhibits its activity by preventing it from reaching the nucleus where it acts as a transcriptional regulator.   Furthermore, compelling new data in animal models indicate that itanapraced blocks both the expression and neurotoxicity of  LRRK2 and, therefore, shows strong potential to be disease modifying in Parkinson’s disease patients. CereSpir aims to initiate Phase 2 trials in 2019.