Dosing Begins in Phase 2a Trial of Oral Treatment to Aid Cognition

Parkinson's patients with mild cognitive problems being given CST-2032

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Patient dosing has begun in a Phase 2a clinical trial testing oral CST-2032 in combination with CST-107 as a potential way to ease the symptoms of mild cognitive impairment and mild dementia due to Parkinson’s or Alzheimer’s disease, the company developing these therapies, CuraSen Therapeutics, announced.

The trial (NCT05104463) follows positive findings in a Phase 1 multiple-dose study of CST-2032/CST-107 in healthy volunteers and patients with mild cognitive impairment, the company stated in a press release. CuraSen plans to present these findings at a future medical conference.

Enrollment of about 40 eligible patients, ages 50 to 80, in the placebo-controlled Phase 2a study is underway at various U.S. sites and in New Zealand, CuraSen stated. According to the study’s NCT document, eligible Parkinson’s patients are those with rapid eye movement (REM) sleep behavior disorder, which is linked to more severe symptoms and faster disease progression, but no hallucinations.

Trial contact and U.S. site location information is available.

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Patients with neurodegenerative diseases, such as Parkinson’s and Alzheimer’s, experience  dysfunction in a brain region called the locus coeruleus. This occurs early in disease processes, sometimes years before symptoms first appear.

The locus coeruleus is the main site for production of norepinephrine, also called noradrenaline, in the brain. Norepinephrine is both a hormone and a neurotransmitter, and it binds to and activates beta-2 adrenergic receptors in the brain. By doing so, it helps control attention and focus, mood, learning, memory, and sleep. A lack of norepinephrine can cause a range of symptoms, including cognitive impairment.

Oral CST-2032 aims to ease mild cognitive deficits

CST-2032 is an agonist, or activator, of beta-2 adrenergic receptors. It is designed to mimic the action of norepinephrine and to compensate for its loss in the brain of patients, potentially easing cognitive symptoms. CST-107 is administered with CST-2032 minimize known side effects of beta-2 adrenoceptor agonists like an increased heart rate, tremor and palpitations, which can limit dosing to below a therapeutic threshold.

The ongoing trial’s goal is to evaluate CST-2032/CST-107’s safety versus a placebo, and how well it works to improve cognition in adults with mild cognitive impairment or mild dementia due to Parkinson’s or Alzheimer’s. 

All patients will be treated with CST-2032, at a daily dose of 3 or 6 mg, of  for two weeks in combination with 3 mg of CST-107.

The study has a crossover design, meaning that all enrolled initially will be randomized to either CST-2032/CST-107 treatment or a matching placebo for 14 days. Then, after a seven-day washout, treated patients will move to placebo and those on placebo will be given CST-2032/CST-107 for another 14 days.

Blood samples will be collected before, during, and after treatment administration to determine the therapy’s pharmacodynamics, which measures the interactions between the body and a pharmacological compound.

After each of the treatment’s two weeks, researchers will assess side effects and monitor patients’ blood pressure and heart rate. As secondary trial goals, they will also measure changes in attention, memory, motor coordination, learning, and recognition of basic facial emotions.

If encouraging results are found in this Phase 2a study, whose results are anticipated early next year, another and longer Phase 2 trial is planned with additional doses of CST-2032/CST-107, CuraSen stated.

A separate adrenergic compound, called CST-103, is being tested in a Phase 2 clinical trial (NCT04739423) that has recruited 41 patients with one of four neurodegenerative disorders: Parkinson’s disease with REM sleep behavior disorder, Parkinson’s disease dementia, mild cognitive impairment, and Lewy body dementia. CST-103, which is also given in combination with CST-107, was reported to increase blood flow to certain brain regions in a Phase 1 trial in eight people with Parkinson’s or mild cognitive impairment.

Patients in this crossover study, taking place in Europe, New Zealand and Australia, are also being treated with CST-103/CST-107 or given a placebo for 14 days. Its main goals are changes with treatment related to cognitive and executive function, mood, attentiveness, arousal, and bioactivity. The trial is reported to have concluded in August and its findings could help identify patients with common core symptoms that are most likely to respond to treatment.

“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,” said Anthony Ford, PhD, CuraSen’s CEO.

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