Positive phase 2 results reported for novel combination therapy for Parkinson’s disease

Key takeaways:

• Clenbuterol/nadolol combination therapy demonstrated significant improvements in episodic memory, attentiveness and depressive emotional bias.
• No serious drug-related adverse events were reported.

CuraSen Therapeutics Inc. announced positive data from its randomized, double-blind crossover phase 2 study of CST-103/CST-107, which demonstrated improvements in cognition and mood in those with Parkinson’s disease.

According to a CuraSen release, the study — which took place at locations in Australia, Belgium, New Zealand and the U.K. — evaluated the novel combination of CST-103, also known as clenbuterol, and CST-107, known as nadolol, a beta adrenoreceptor blocker.

The combination therapy, said to restore adrenergic stimulus to the brain, was tested in 25 patients with PD and cognitive deficits, as well as 13 individuals with mild cognitive impairment without a PD diagnosis. Participants received either once daily clenbuterol 80 µg/nadolol 1 mg combination or placebo, each for 14 days with at least 14 days of washout between treatments. All participants with PD had impaired cognition at baseline with evidence of impaired cerebral noradrenergic signaling, assessed via neuromelanin MRI of the locus coeruleus.

Results showed significant improvements in episodic memory, attentiveness and depressive emotional bias in patients treated with the combination therapy, as well as rapid onset of improvement as early as one day after treatment, which persisted beyond the 14 days of treatment. No serious or severe adverse events attributed to the drug were reported, according to the release.

A phase 2 study with clenbuterol/nadolol is expected later this year and will enroll individuals diagnosed with PD who have significant nonmotor symptoms, with a similar combination dosing plan over 12 weeks.

“For the first time, we have been able to show improved outcomes in cognition and mood with adrenergic agonism in patients with neurodegenerative disease, by safely restoring a stimulus to the brain that is lost early in the pathologic process,” Anthony Ford, PhD, CEO at CuraSen, stated in the release. “With its strong safety profile and impressive effect sizes in key domains, we look forward to testing this fast-acting combination treatment in a longer-term study in Parkinson’s patients later this year.”

The company also announced promising results from a phase 1 study of CST-2032, a beta-2 adrenoreceptor agonist, and nadolol combination therapy in 79 healthy individuals and patients with mild cognitive impairment. Participants were divided into single-ascending and multiple-ascending dose cohorts.

Per the release, the treatment was safe and well-tolerated and increased cerebral blood flow in regions of the brain involved with memory, alertness and arousal. Results also showed positive performance changes in cognitive tasks associated with memory and provided information on optimal combination dose levels of each substance.

Based on these results, the company has launched an exploratory, randomized, placebo-controlled, double-blind phase 2a crossover study of CST-2032/CST-107 in up to 60 patients with mild cognitive impairment or mild dementia due to PD or Alzheimer’s disease. The trial is being conducted at 20 centers in the U.S. and New Zealand, and results are expected later in 2023.