Technology Certain neuroactive steroids are key drivers of this increased GABA signaling, causing impaired cognitive and motor function, and sedation.
Hepatic encephalopathy (HE) is a serious neuropsychiatric and neurocognitive complication in acute and chronic liver disease. HE is characterized by impairments of the sleep-wake cycle, consciousness, cognition, memory, decreased energy levels, personality change and reduced motor skills. The disorder therefore has detrimental effects on health related quality of life as a consequence of these diverse and debilitating symptoms.The pathophysiology of HE is driven by reduced liver function through cirrhosis as this increases the ammonia load in the systemic circulation which leads to hyperammonemia and neuroinflammation. The main symptoms of hyperammonemia arise in the brain where impaired neural signaling and cerebral edema gives the characteristic symptoms of HE. An increase in the inhibitory ‘GABAergic tone’ in the CNS is a credible main driver for the clinical signs and symptoms.
Umecrine Cognition is developing pharmaceuticals to treat acute life-threatening HE and long-term maintenance in minimal HE caused by endogenous GABA-steroids. Certain neuroactive steroids are key drivers of this increased GABA signaling, causing impaired cognitive and motor function. This makes neurosteroid-antagonists a credible therapeutic class to explore for novel treatments in HE. The expected effects of treatment include shortened hospital stay and need for intensive care with improved and maintained cognitive and motor function resulting in improved quality of life and reduced social costs.
A therapy based on this mode of action is the first potential treatment that directly addresses the neurocognitive signs and symptoms of HE. Treatment would only be required when motivated by a worsening of these symptoms, whereas present options all require prophylactic use to reduce the risk of recurrent episodes by aiming to control hyperammonemia. Currently, there are no drugs available that directly addressing the signs and symptoms of HE. The treatment can therefore potentially be combined with present standard of care. Umecrine Cognition’s innovation represents a unique and novel treatment principle and no similar substances exist that targets the effects of endogenous and exogenous CNS-steroids.