New PDD/LBD Treatment Tested in UB Clinical Trial

After Alzheimer’s disease, LBD and related Parkinson’s disease dementia (PDD) are some of the most common types of dementia affecting older adults; but they are severely understudied.

While LBD patients are often prescribed medications that treat psychosis and Alzheimer’s disease, there are no medications designed specifically to treat LBD.

Eli Lilly and Company has launched a clinical trial in hopes of changing that.

“Participating in this trial could help push this drug more quickly through the pipeline,” says Kinga Szigeti, MD, PhD, associate professor of neurology, who is principal investigator at UB.

LBD and PDD affect an estimated 1.4 million Americans. The condition often occurs after a patient has been diagnosed with Parkinson’s disease, the symptoms of which often begin with the inability to control movements but then progress to affect cognition.

In LBD, cognitive decline is the first symptom, frequently followed by Parkinsonian features. Both diseases are characterized by abnormal protein deposits called alpha-synuclein, which form Lewy bodies in the neurons.

A key distinction between PDD and most other kinds of dementia are the neuropsychiatric symptoms that can occur — such as hallucinations and Capgras delusion or “impostor syndrome” — where patients believe that a loved one has been replaced by an identical impostor.

“The neuropsychiatric symptoms can make this kind of dementia much more challenging for families to deal with than Alzheimer’s disease,” Szigeti says.

PDD symptoms also include a tendency to sleep for long periods at a time, sometimes 14-16 hours per day.

“Sleeping so much can cause patients to lose muscle mass, becoming more frail and more prone to infection,” Szigeti explains. “Changes in the nervous system can lead to an unhealthy drop in blood pressure and patients become more prone to falls.”

For these reasons, she notes, patients with this kind of dementia have a lifespan that is much shorter than for Alzheimer’s patients.

“Lewy body dementia has been very understudied in clinical trials,” Szigeti says.

While some medications used to treat psychosis can mitigate certain aspects of LBD, many of them also increase the risk of stroke or even death.

“For that reason, many patients and their families feel they have no options,” Szigeti says. “They find themselves between a rock and a hard place.”

But now, Western New York patients have an opportunity to participate in the first clinical trial to test a medication for LBD at the Jacobs School.

The advantage of the new drug — known as LY3154207 — is that it has a novel mechanism of action on dopamine, the brain chemical that Parkinson’s disease rapidly depletes.

The drug was designed to maximize the brain’s response to the remaining dopamine, therefore improving cognition, motor function and boosting wakefulness. It is taken in pill form.

“We are for the first time offering hope to these patients and their families, and an opportunity to participate in this trial,” Szigeti says.

Interested patients will be seen at UBMD Neurology, where Szigeti is director of its Alzheimer’s Disease and Memory Disorders Center.