People living with dementia with Lewy bodies (DLB) often face a difficult mix of symptoms—changes in thinking, movement, behavior, sleep, and daily function. Right now, there are no FDA-approved medications specifically for DLB, and most available treatments address only pieces of the condition. That is why new research into potential therapies is so important.

A recently published Phase 2 clinical trial tested an investigational drug called zervimesine (also known as CT1812) in people with mild-to-moderate DLB. The study offers early but encouraging information about safety and possible benefits—and helps guide what future trials should look like.

What is zervimesine?

Zervimesine is designed to protect the connections between brain cells. Called synapses, these connections are essential for brain functioning. In DLB, toxic clumps of misfolded protein—especially alpha-synuclein, and often amyloid—can interfere with these connections. Zervimesine works by making it more difficult for these toxic proteins to interact with the synapses between brain cells.

The drug has already been studied in Alzheimer’s disease. This trial was the first to test it specifically in people with dementia with Lewy bodies.

How was the study done?

The study, called SHIMMER, enrolled 130 adults aged 50 to 85 with mild-to-moderate DLB at 31 sites across the United States. Participants were randomly assigned to receive:

• zervimesine 100 mg,
• zervimesine 300 mg, or
• a placebo (an inactive “sugar pill”),

taken once daily for about six months.

Neither the participants nor the researchers knew who was receiving which treatment until the study ended. This type of design—called double-blind and placebo-controlled—helps reduce bias and makes results more reliable.

The main goal of the study was to evaluate safety and tolerability. Researchers also explored how the drug might affect cognition, behavior, daily function, movement, sleepiness, and caregiver distress.

What did the study find about safety?

Overall, zervimesine was found to be safe and generally well tolerated, especially at the lower 100 mg dose.

• Most side effects were mild or moderate.
• The most common issues were falls, headache, dizziness, and stomach-related symptoms.
• A small number of participants—more often at the higher 300 mg dose—developed temporary increases in liver enzymes. These resolved after stopping the medication and did not lead to serious liver injury.
• Importantly, discontinuation rates for side effects were similar between the 100 mg dose and placebo, while higher with the 300 mg dose.

These findings suggest that lower doses may offer a better balance of safety and potential benefit, an important insight for future trials.

What did the study find about symptoms?

This was an exploratory study, meaning it was not designed to prove effectiveness. Still, the results showed consistent trends favoring zervimesine over placebo across many DLB-related symptoms.

Compared with people taking placebo, those receiving zervimesine showed signs of:

• Slower worsening of neuropsychiatric symptoms, including hallucinations, anxiety, and agitation.
• Reduced caregiver distress, possibly reflecting less day-to-day burden.
• Better preservation of daily functioning, such as managing basic activities of daily living.
• Less progression of movement symptoms.
• Reduced cognitive fluctuations, a hallmark symptom of DLB.

While some cognitive tests showed variability and did not reach statistical significance, the overall pattern across symptom domains was consistent and encouraging.

What this means for people with DLB

For people affected by DLB, these results offer measured hope. While this was a Phase 2 study and researchers will not know if zervimesine is truly safe and effective until Phase 3 trials are completed, the study provides a signal that targeting synaptic health may help address multiple symptoms at once.

Equally important, the study showed that treating behavioral symptoms did not worsen movement symptoms, a concern with some medications. And the reduction in caregiver distress highlights something families know well: even small changes can make a meaningful difference in daily life.

What comes next?

Because this was a small, early-phase study, the results need to be confirmed in larger and longer trials. The findings help researchers decide:

• which dose to study next,
• which symptoms to focus on, and
• which outcome measures best capture meaningful change in DLB.

Zervimesine remains an investigational drug and is not yet approved for clinical use. But this study represents an important step forward in the search for treatments that reflect the full complexity of dementia with Lewy bodies.

How can I get involved?

Finding safe and effective treatments for Lewy body dementia takes research, and research takes people like you.

For more information on clinical trials and other studies that might be right for you, LBDA encourages you to visit our clinical trials page. To stay up-to-date on new studies when they launch, you can also sign up for LBDA’s Lewy Trial Tracker.

Reference

Galvin JE, Tolea MI, Scharre DW, Hamby ME, Iaci JF, Grundman M, and Caggiano AO. 2025. Phase 2 study of zervimesine (CT1812) in participants with mild-to-moderate dementia with Lewy bodies (DLB). Alz Dem 21(12):e71004. DOI https://doi.org/10.1002/alz.71004