basal ganglia

Omeros‘ lead compound from its phosphodiesterase 10 (PDE10) programme, OMS824, has achieved around 50% occupancy of PDE10 without causing movement disorders in a Phase I clinical trial.

The study was designed to measure the extent of the compound’s binding activity to PDE10 in the basal ganglia, a region of the brain that is associated with various diseases affecting cognition, such as Huntington’s and schizophrenia.

Healthy subjects, who were administered with OMS824 once each day for seven days in the trial, were measured for binding activity using positron emission tomography (PET) scans.

OMS824 was well-tolerated and the only recorded adverse effect was mild somnolence, a finding supported by previous studies.

The investigational agent did not trigger extrapyramidal symptoms such as loss of muscle control, including muscle rigidity, tremors or involuntary muscle movements, which are commonly reported as side effects with other PDE10 inhibitors.

Omeros chairman and chief executive officer Dr Gregory Demopulos said the data underscored the unique pharmacology of OMS824.

"To our knowledge, this is the first time that a PDE10 inhibitor has demonstrated this level of enzyme occupancy without associated extrapyramidal symptoms, a side effect commonly seen with antipsychotic drugs," Demopulos said.

"These results could translate into a significant competitive advantage across a wide range of CNS indications."

Having already demonstrated tolerability and pharmacokinetics at multiple doses in healthy subjects in Phase I clinical programme, the PDE10 inhibitor will be advanced into Phase II clinical trials in Huntington’s disease and schizophrenia by the end of 2013.

Image: Coronal slices of human brain showing the basal ganglia. White matter is shown in dark gray, gray matter is show in light gray. Photo: Courtesy of Andrew Gillies.