Brain pacemaker may help reduce Parkinson’s disease symptoms

An implanted device regulated by the body’s brain activity could provide continual and improved treatment for the symptoms of Parkinson’s disease (PD) in certain people with the disorder.

This type of treatment, called adaptive deep brain stimulation (aDBS), is an improvement on a technique that has been used for PD and other brain disorders for many years.

The small feasibility study funded by the National Institutes of Health (NIH) found that aDBS was markedly more effective at controlling PD symptoms compared to conventional DBS treatments.

“This study marks a big step forward towards developing a DBS system that adapts to what the individual patient needs at a given time,” said Megan Frankowski, Ph.D., program director for NIH’s Brain Research Through Advancing Innovative Neurotechnologies® Initiative, or The BRAIN Initiative, which helped fund this project.

“By helping to control residual symptoms while not exacerbating others, adaptive DBS has the potential to improve the quality of life for some people living with Parkinson’s disease.”

Deep brain stimulation

DBS involves implanting fine wires called electrodes into the brain at specific locations. These wires then deliver electrical signals that can help mitigate the symptoms of brain disorders such as PD. Conventional DBS provides a constant level of stimulation and can also lead to unwanted side effects, because the brain does not always need the same strength of treatment.

Therefore, aDBS uses data taken directly from a person’s brain and uses machine learning to adjust the level of stimulation in real time as the person’s needs change over time.

Four people already receiving conventional DBS were first asked what they felt was their most bothersome symptom that had persisted despite treatment. In many instances this was either involuntary movements or difficulty in initiating movement.

The participants were then set up to receive aDBS treatment alongside their existing DBS therapy. After training the aDBS algorithm for several months, the participants were sent home, where the comparison test was performed by alternating between conventional and aDBS treatments. Changes occurred every two to seven days

aDBS improved each participant’s most bothersome symptom roughly 50% compared to conventional DBS. Notably, even though they were not told which type of treatment they were receiving at any one time, three of the four participants were often able to correctly guess when they were on aDBS due to noticeable symptom improvement.

This project is a continuation of several years of work led by Philip Starr, M.D., Ph.D., and colleagues at the University of California, San Francisco. Previously, in 2018, they reported the development of an adaptive DBS system, referred to as a “closed loop” system, that adjusted based on feedback from the brain itself. Later, in 2021, they described their ability to record brain activity in people as they went about their daily lives.

Here, those two findings were combined to use brain activity recorded during normal life activities to drive the aDBS system. However, DBS treatment changed brain activity so much that the signal that had been expected to control the aDBS system was no longer detectable. This required researchers to take a computational and data-driven approach to identify a different signal within the brains of people with PD who were receiving conventional DBS therapy.

Conventional treatment for Parkinson’s disease often involves the drug levodopa, which is used to replace dopamine in the brain that has been lost because of the disorder. Because the amount of the drug in the brain fluctuates, peaking shortly after administration of the drug and gradually decreasing as it is metabolized by the body, aDBS could help smooth out the fluctuations by providing increased stimulation when drug levels are high and vice versa, making it an attractive option for patients requiring high doses of levodopa.

While these findings are promising, there remain significant challenges to overcome for this therapy to be more widely available. The initial setup of the device requires considerable input from highly trained clinicians. Researchers envision a future where most of the work would be managed by the device itself, greatly reducing the need for repeat visits to the clinic for fine tuning.

This type of automation is also necessary for other groups to test and eventually offer aDBS therapy in a clinical setting.

“One of the big issues facing DBS, even in approved indications like Parkinson’s, is access, both for patients in terms of where they can get it and also the physicians who need special training to program these devices,” said Frankowski.

“If there were a way for a system to find the most optimal settings at the press of a button, that would really increase the availability of this treatment for more people.”

Parkinson’s UK invests in developing potential new drug

Parkinson’s UK has confirmed it is investing £1.6m through its Virtual Biotech programme to drive the development of a promising molecule which has the potential to become a drug that slows or stops Parkinson’s.

Parkinson’s UK is partnering with US-based company Acurex Biosciences to support the final stages of testing and development of their molecule, CU-13001, in preparation for its progress into clinical trials.

CU-13001 is a molecule that has shown exciting potential for protecting the brain cells that are lost in Parkinson’s in laboratory-based tests. It targets an enzyme called 15-lipoxygenase, which emerging research suggests may play an important role in the death of dopamine-producing cells in the condition.

Mark Kaufmann, CEO of Acurex, stated: “We are beginning to understand that 4-HNE, a toxic byproduct of lipid metabolism, might be a central cause of Parkinson’s. Inhibitors of 15-lipoxygenase could stop the production of 4-HNE and potentially halt the disease.

“We aim to test this hypothesis in human trials soon, and partnering with Parkinson’s UK is a critical step in this process.”

Acurex has developed a molecule with the properties needed to get into the brain and protect brain cells. To move CU-13001 forward, essential preclinical tests are needed to meet regulatory requirements before it can be given to patients for the first time in clinical trials.

The tests will assess potential side effects, potential interactions with other common medications, and how the molecule is distributed and processed in the body.

Before going into human trials, regulatory guidelines require new drugs to be tested for safety in 2 animal species: a rodent and a non-rodent. If successful, CU-13001 will be ready for clinical trials.

Arthur Roach, Virtual Biotech Director at Parkinson’s UK, said: “We’re delighted to partner with Acurex Biosciences to accelerate this exciting new potential treatment for Parkinson’s through our pioneering Virtual Biotech programme.

“CU-13001 targets a novel mechanism for Parkinson’s and represents an exciting new approach to slowing or stopping the death of brain cells in the condition.

“This is what we created the Virtual Biotech programme to do, apply support from the Parkinson’s community to accelerate bold new research to create potentially life-changing new therapies. We look forward to working with Acurex to advance CU-13001 towards clinical trials.”