Cognition: OCCT-lynx1 siRNA
Ophidion is developing therapeutic interventions to treat the cognitive dysfunction associated with mental and neurological disorders, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and other brain diseases (including rare diseases associated with cognitive dysfunction).
We are capitalizing on the pioneering work of Dr. Miwa related to the impact of knocking out the lynx1 on regulating cholinergic tone and consequent enhancement of learning and memory function. Lynx1 inhibits learning and memory. Removing lynx1 genetically improves memory (Miwa, Neuron 2006) and restores youthful plasticity (Morishita, Science, 2010). Release of this molecular brake can unmask cholinergic-dependent mechanisms in the brain. This understanding of the relationship of lynx1 and cognition has enabled us to knock down lynx1 mRNA with siRNA to enhance cognition and memory. Ophidion is seeking to modulate this regulator by inducing transcriptional changes of lynx genes achieved in response to pharmacological interventions with our therapeutic products.
In order to create a therapeutic intervention recapitulating this cognitive enhancement of the lynx1 knockout animals, Ophidion has developed an RNAi therapeutic to enhance cholinergic tone in the brain through gene silencing of the lynx1. Ophidion has used its novel and proprietary OCCT carrier system to deliver therapeutic siRNA directed at lynx1 into the brain to achieve a desirable target pharmacological endpoint required to deliver meaningful efficacy in cognitive enhancement. We believe this compelling biological proof of concept in rodent models is transferable to nonhuman primates and to humans as this gene is conserved across species.
About Diseases of Cognitive Benefits
Cognitive impairment remains an area of significant unmet need for patients across a broad range of neurological disorders. Cognitive dysfunction is a common and significant non-motor symptom of many neurological disorders like Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD). The societal costs of neurodegenerative diseases are enormous. Activities of daily living for a normally functional person (e.g. household activities, handling of money, shopping, transportation) have a high demand for cognitive functions. Maintenance of normal cognitive function is the most important aspect about a good quality of life and living an independent life in society.
Alzheimer’s disease (AD) is the most common cognitive dementia, affecting one of every ten people over age 65 and nearly 35% over age 85. This translates into more than 5.4 million AD patients in the US alone, a number expected to reach 9 million by 2030 and 16 million by 2050 as the US population ages. In the US alone, the economic burden of AD is estimated to be in excess of $110B annually.
Parkinson’s disease (PD) is an extremely diverse disorder. Parkinson’s affects about one million people in the United States and ten million worldwide. The main finding in brains of people with PD is loss of dopaminergic neurons in the area of the brain known as the substantia nigra. Despite increased understanding of pathological, neurotransmitter and genetic drivers, there are no proven pharmacological treatments for PD’s mild cognitive impairment.