Advanced Therapies in Parkinson Disease: Matching the Right Treatment to the Right Patient

As treatment options for Parkinson disease (PD) continue to expand, clinicians increasingly have to consider when patients may benefit from device-aided therapies and which approach is best suited to their individual needs. Infusion therapies, deep brain stimulation (DBS), and focused ultrasound each offer potential benefits, but also come with distinct practical considerations and limitations.

At the 2026 International Congress of Parkinson’s Disease and Movement Disorders (MDS), held October 4-8 in Seoul, South Korea, Hubert Fernandez, MD, will deliver a plenary presentation focused on advanced therapies in PD, with an emphasis on nonoral pharmacological approaches and device-aided therapies. Fernandez, who is the director of the Center for Neurological Restoration and Head of Movement Disorders at Cleveland Clinic, will examine how clinicians can determine when patients may be ready to transition beyond oral medications and how different treatment options may fit into an individualized treatment strategy.

Ahead of MDS 2026, Fernandez spoke with NeurologyLive® about the evolving landscape of advanced therapies in PD. In the discussion, Fernandez outlined considerations for selecting among infusion therapies, DBS, and focused ultrasound, highlighted signs that may prompt clinicians to discuss device-aided treatment with patients, and discussed ongoing efforts to make these therapies more accessible, tolerable, and user-friendly.

NeurologyLive: Can you describe your plenary presentation on advanced therapies in PD and what you hope clinicians take away from the discussion?

Fernandez, MD: I'm really excited to give this plenary talk at MDS in Seoul, South Korea. The topic I was given is advanced therapies in PD. The focus of my plenary talk will not be on oral pharmacological therapies, but mainly on nonoral pharmacological therapies.

In particular, there is a boom of percutaneous and subcutaneous infusion therapies for PD. I'm going to be talking about these device-aided therapies in PD, except deep brain stimulation surgery and surgical procedures, because that is a different talk that was assigned to a different speaker.

Now that there are several advanced therapy options for PD, how do you view about matching the right therapy to the right patient?

That is a particularly big challenge. There is a spectrum of therapies that a patient with PD may come across in his or her journey with the disorder. Early on in the disease, they might be quite satisfied with oral pharmacological therapy. At some point, they may experience motor fluctuations, which requires them to have adjunctive oral therapies.

At some point, even those adjunctive therapies and combinations of oral medications may not be sufficient to keep the patient in a steady state and maintain a good “on” period. This is where we consider infusion therapies, which could be percutaneous through the gut or subcutaneous through the skin, deep brain stimulation surgery, or ultrasound therapy.

Each patient may fall into a different algorithm for a device-aided therapy. Some of them may actually qualify for any or all of them, and it will be a matter of choosing their preference, the doctor's comfort level, or some relative indication or contraindication for one device-aided therapy or another. One of the aims of my talk is to help guide clinicians on which particular patients would be eligible for which type of device-aided therapy.

Looking ahead, what work is still needed to better determine when patients should transition to device-aided therapy, and where do you see individualized treatment headed?

There is quite a bit of work, particularly in terms of real-world outcomes, that we still need to evaluate as to when a patient with PD requires device-aided therapy. In some parts of the world, or sometimes in a big country like the United States, patients could be waiting longer than they should be for a device-aided therapy. In some countries, they may not be offered this or even hear about this. The question of when to transition and how to offer this to more patients around the world is a challenge that needs to be determined moving forward.

The second issue is that each of these device-aided therapies has advantages and disadvantages. For example, percutaneous infusion therapy has the disadvantage of requiring a procedure for a tube to be placed through the stomach and ending in the small intestine for maximal absorption. It carries the intrinsic disadvantage of maintaining that tube and the clunkiness of that system.

This is in part alleviated by subcutaneous infusion therapies, where a tiny needle is placed on the skin and levodopa and other medications, such as apomorphine, are infused constantly, drip by drip, second by second throughout the day. This is a much easier procedure, but it can carry a significant skin burden, and not all patients can tolerate that therapy. Each treatment has an advantage and a disadvantage and we still need to continue our work in making these device-aided therapies more maintenance-free and user-friendly for the patients who are using them.

The third issue is the global economic impact of these device-aided therapies. They're not the cheapest medications. On the other hand, if they prevent long-term care placement, prevent hospitalizations, or improve mortality in patients with PD, then they may actually be cost-saving in the end. The pharmacoeconomic impact of these device-aided therapies will also need to be addressed moving forward.

For a patient who is not quite ready for an advanced therapy, what signals are you watching for that would tell you it is time to have that conversation?

Not everyone would be physically ready for it, and sometimes, patients aren’t ready psychologically or financially for this. From the PD standpoint, candidates we would consider offering device-aided therapy to are patients with longer-standing PD. This would include patients who have had PD for at least 3 to 5 years and sometimes longer than that.

Patients who could be considered eligible have tried and failed oral pharmacological therapy and are experiencing significant motor fluctuations. This is a very personal criterion as to when it is significant. It is a person-to-person call as to whether this is burdensome.

But as a general rule, someone who has “off” periods of more than 3 or 4 hours per day or someone who is having significant dyskinesias may be a candidate. These are the involuntary extra movements that are seen in patients taking levodopa.

When the dyskinesias are bothersome, when the “off” periods are more than 3 hours or so, or when patients have tried various medications and are unable to tolerate them or unable to relieve their motor fluctuations, these are the red flags that, when we see them, we start entertaining the possibility of offering device-aided therapy.

DBS has been used in PD for decades, with substantial long-term data. What has follow-up taught us about its benefits and when in the disease course to intervene?

The great news is that DBS is probably one of the device-aided therapies that has advanced the most. This technology is growing and progressing by leaps and bounds. As an example, the clunkiness of the system for infusion therapies that we're currently working on has been tackled with DBS because it predated them. Researchers have addressed these practical limitations sooner than the other device-aided therapies.

Batteries and implantable devices are now thinner on the chest wall and stronger. We now have batteries that are rechargeable, so they don't need to be replaced every 5 years like they did before. We can now program these DBS devices remotely, and therefore geographic limitation is no longer an issue for a lot of patients.

The programming itself has become more and more sophisticated. We have been using devices that help automate or accelerate finding the sweet spot for these deep brain stimulation devices.

We also have brain-sensing technology now. The brain emits certain signals when patients need more stimulation from the deep brain stimulation device and when they need less. The devices that we've implanted now have a way of sensing these signals and automating the amount of voltage or current that is delivered to the brain.

These are exciting times for deep brain stimulation surgery, and I suspect it's going to get even better. Just like infusion therapies will likely become smaller, better tolerated underneath the skin, less likely to kink if they are percutaneous devices, more enduring, and easier to manage for patients with PD.

Focused ultrasound has also grown as a noninvasive option, although its use has historically been more limited. Where does it realistically fit into the treatment paradigm today?

High-frequency ultrasound is also evolving at a fast pace, just like deep brain stimulation surgery and infusion therapies for PD. They're all marching alongside each other, making things better and better. A few things we're looking forward to with focused ultrasound are being able to offer focused ultrasound on both sides of the brain and therefore tackling symptoms on either side or both sides of the body.

Before, it was primarily offered for tremors and only on one side of the brain, and therefore only on one side of the body, now we can do staged bilateral high-frequency ultrasound, which then alleviates tremors on both sides. We also have new FDA-approved targets that would alleviate not only tremor, but also stiffness and slowness and other motor symptoms of PD.

Even the high-frequency ultrasound targets that we offer now are expanding. Soon enough, patients will have an option of doing either deep brain stimulation surgery or high-frequency ultrasound for the same symptoms that they're currently suffering from.

Is there anything else about your talk or the broader advanced-therapy landscape that you would like to emphasize?

I think the challenge of using infusion therapies in PD is when to offer them to patients. Sometimes we offer them too soon, and they would have been just as happy with oral therapies. Sometimes it's a little bit too late.

The second challenge is what kind of infusion therapy to offer, and whether that would be better or worse than other device-aided therapies such as deep brain stimulation surgery or high-frequency ultrasound therapy.

The talk is going to focus on these options and untangling some of these difficult choices. I'm really looking forward to it, and hopefully we keep advancing the science for the treatment of PD.

Transcript edited for clarity. For more MDS coverage, click here!