Addressing Cognitive Impairment by Silencing a Novel Target That Acts As the “Break on Memory”


Cognition: OCCT-lynx1 siRNA

Ophidion’s Cognition Enhancement Program capitalizes on Dr. Julie Miwa’s pioneering research on lynx1 gene’s regulation of cholinergic-based learning and memory. Silencing lynx1 in mice improves memory (Miwa, Neuron 2006) and restores youthful plasticity (Morishita, Science, 2010) by releasing a molecular brake on cholinergic-based neural plasticity. Ophidion’s OCCT-complexed siRNA directed at lynx1 achieved ~80% knock down with a corresponding 6.8x memory enhancement in wild-type mice (Figure 2). This pre-clinical proof-of-concept should be transferable to nonhuman primates and humans since lynx1 is conserved across species.


Figure 2. OCCT-lynx1 siRNA improves memory. Increased novel object recognition memory was observed in OCCT-lynx1 siRNA treated mice.


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 nonmotor 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 of 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 the brains of people with PD is the 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.