HT-0712 is an inhibitor of phosphodiesterase 4 (PDE4). PDE4 catabolizes cyclic AMP, elevated levels of which lead to activation of CREB. Phase 1 studies have shown HT-0712 to be well-tolerated in young and elderly subjects. A Phase 2a study, carried out for 28 days in elderly subjects with age-associated memory impairment (AAMI), also showed HT-0712 (i) to be well-tolerated, (ii) to have no effects on measures of short-term (working) memory, (iii) to have no effects on passive EEG measures and (iv) to have a statistically significant effect at one dose on long-term memory of word list recall. Phase 1 studies have begun with a PDE4 BackUp compound.
MAO-B is an outer mitochondrial membrane flavoenzyme involved in catabolism of neurotransmitters and exogenous amines. MAO-B predominates in the human brain and is responsible for the breakdown of dopamine, a neurotransmitter important for memory formation. Selective inhibition of MAO-B results in elevations of dopamine and thereby may enhance memory formation. Clinical studies of an in-house Lead Compound, HT-3951, currently are underway, and a back up compound has been identified.