CuraSen Therapeutics (CuraSen) has begun dosing patients in a phase 2a clinical trial testing oral CST-2032 – a beta-2 adrenoceptor agonist – in combination with CST-107 – a beta adrenoceptor blocker, to minimise known side effects of beta-2 adrenoceptor agonists – as a potential treatment of mild cognitive impairment or mild dementia due to either Parkinson’s or Alzheimer’s disease, the clinical-stage company announced.
The multi-centre trial, which is expected to enrol approximately 40 patients, is being conducted in the US and New Zealand and follows positive results from a phase 1 study evaluating the safety and tolerability of CST-2032/CST-107 at multiple doses in both healthy volunteers and patients with mild cognitive impairment.
Patients with neurodegenerative diseases, such as Parkinson’s or Alzheimer’s, experience dysfunction in a brain region called the locus coeruleus (LC) very early in the disease process, decades before functional decline.
The LC, known as a key orchestrator of arousal and brain health, delivers most adrenergic input to forebrain structures and activates beta-2 adrenoceptors essential for maintaining mood, memory and cognition.
When the LC declines, cerebral neuroprotection is undermined by loss of these functions, triggering the pathological hallmarks of neurodegenerative disease and progressive loss of cognitive strength.
The company’s two distinct drug candidates, CST-2032 and CST-103, target brain beta-2 adrenoceptors to directly activate cell types normally regulated by healthy adrenergic function.
The stimulatory activation of these cells helps compensate for critical brain functions lost early in the disease process due to adrenergic decline. Moreover, this mechanism of action helps maintain cognition and restore complex pathways vital for protecting brain health.
In the phase 2a randomised, double-blind study, trial participants receive daily doses of CST-2032 (co-administered with CST-107), or matching placebo, for 14 days, followed by a one-week washout period before crossing over to the other arm.
Following completion of the trial, expected early next year, CuraSen plans to initiate longer phase 2 studies with additional dose levels of CST-2032/CST-107 in preferred patient populations, the company outlined.
Anthony Ford, chief executive officer, CuraSen, said: “With this trial initiation, CuraSen now has two unique pipeline opportunities in ongoing phase 2 clinical studies aimed at improving the debilitating cognitive symptoms and loss of function in neurodegenerative diseases, with the ultimate goal of preventing or even reversing disease progression.”