Combination adrenergic activator improves several cognitive domains in patients with AD, PD
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CuraSen Therapeutics has announced positive data from a phase 2a study of its combination adrenergic activator, CST-2032/CST-107, for patients with mild cognitive impairment or mild dementia from Alzheimer’s or Parkinson’s disease.
According to a company release, CST-2032 is an oral, brain-permeant, beta-2 adrenoceptor agonist delivered in combination with CST-107 (nadolol), a brain-sparing beta blocker, to inhibit peripheral effects of beta-2 adrenoceptor agonism. CST-2032 works by enabling reactivation of brain adrenergic function lost early in the neurodegenerative course, like the company’s other lead candidate CST-103, also a beta-2 adrenoceptor agonist.
The randomized, placebo-controlled, double-blinded crossover study at sites in the U.S. and New Zealand evaluated 64 patients with mild cognitive impairment (MCI) or mild dementia from AD or PD. The study objectives were to determine safety and tolerability of CST-2032/CST-107, identify optimal dosing and identify cognitive tests responsive to agonist stimulus within the 2-week dosing period.
Participants received 3 mg CST-2032 with 3 mg nadolol or matching placebo daily for 14 days, followed by a wash-out period of at least 7 days before switching to the other treatment arm. Researchers assessed cognition using the Digit symbol substitution test, Cambridge neuropsychological test battery and facial expression recognition task.
According to the release, CST-2032/CST-107 demonstrated “statistically and clinically important effects” across several domains, including attention, executive function, facial recognition, impulse control and memory. Target effect sizes of at least 0.2 to 0.3 in the study predict success in larger, longer studies.
No serious adverse events were reported, the release stated, with no increases in heart rate observed 1 to 4 hours after dosing.
Later this year, the company plans to initiate longer studies of CST-2032/CST-107 and CST-103/CST-107 in AD and PD patients with MCI, and also develop fixed-dose combination tablets for each drug candidate.
“The robust, collective data set demonstrate that this novel mechanism of action for restoring adrenergic function to the brain is a highly compelling strategy to address unmet symptoms of neurodegeneration,” Anthony Ford, PhD, CEO of CuraSen, stated in the release. “We plan to evaluate additional doses and refine optimal patient profiles in our upcoming phase 2 studies, with the goal to significantly increase cognitive performance and ultimately, halt disease progression.”