Expansion of Neurotech options for people with Parkinson’s disease.

With a global burden that has doubled over the past generation, the prevalence of Parkinson’s disease is now about 6.1 million[i]. This positions PD to be one of the world’s fastest growing neurological disorders. As a slow progressive disease, it is estimated that the economic burden of PD in just the U.S. can be over $79 billion by 2037.

People living with Parkinson’s disease experience an array of both non-motor and motor related symptoms. Some of the symptoms in the non-motor category include fatigue, weight loss, blurred vision, disturbances of smell, or problems sleeping. On the contrary, motor symptoms can be not as subtle. The major motor disturbances in PD are bradykinesia (i.e., slowed movement), hypokinesia (small amplitude movements), resting tremor, rigidity, and postural instability.[ii] About 20% of people over the age of 80 have Parkinsonism associated gait disturbances.

Needless to say, living with Parkinson’s disease is no walk in the park. What can we do about it? There are many resources for managing Parkinson’s disease from advocacy organizations like the Parkinson’s Foundation, the American Parkinson Disease Association, or the Micheal J. Fox Foundation. In the field of neurotechnology, deep brain stimulation has gained ground as a clinical treatment. There have also been neurotechnology innovations in the form of wearables, therapeutic tools and robotic therapies. Here we will explore some of the latest research on preferences and clinical practice around deep brain stimulation for Parkinson’s disease as well as introduce some of the emerging non-invasive technologies.

Clinical and Patient preferences toward Deep Brain Stimulation

According to our partners at Neuromodec, deep brain stimulation is a medical device therapy that requires a surgery to implant a battery-powered neurostimulator (like a pacemaker) in the upper chest. The stimulator is connected to a wire under the skin that leads to an implanted electrode deep in the brain tissue. The technology was introduced for Parkinson’s disease in the early 1990s and has evolved and improved over the years. During that time, there has been knowledge gained on the impact of the technology and a great understanding of preferences among people using the device. For instance, one of the most recent innovations is the development of a closed-loop DBS system, meaning the device can sense when treatment is needed and adapt the stimulation to the needs at that time. A study of five people was conducted at the University of Florida. The treatment was focused on improving medication refractory freezing of gait. Three out of the five participants experienced at least a 40% improvement in freezing of gait [iii]. Today, it is estimated that more than 150,000 people have been implanted with a DBS device.

The basic benefits of DBS have been studied over the years, but one recent consequence draws attention to unanswered ethical concerns. A case study published this year points out that DBS has helped to increase the life expectancy of most people who use the therapy. However, the longevity of living with PD unleashed iatrogenic or disease-state harms that were not expected by the prescribing clinician, caregiver or person receiving the treatment. In addition, the increased lifespan can uncover severe states of the disease reducing quality of life and increasing caregiver burden. The study was published in the Journal of Medical Ethics [iv].

In a study published in 2020, a team of researchers from the U.S. and Europe found that over a 24 month period, DBS therapy resulted in a significant improvement in social, occupational and psychosocial functioning among those who have DBS therapy when compared to the standard medical therapy. This was observed in people who were under the age of 60 and interventions were taken early in the diagnosis of motor complications due to PD [v].

To gain a better perspective of people living with PD and their understanding and impressions of surgical therapies, a team from Thomas Jefferson University surveyed 120 people from an urban movement disorder clinic. They found that among the respondents more people were agreeable to a reversible, minimally-invasive and incisionless surgery. Over half thought DBS is an effective treatment for PD but were concerned about the expense and that it may not be covered by health insurance. Over three quarters of the respondents found DBS to be an invasive therapy [vi].

Perspective on alternative therapies

DBS is one tool to manage the symptoms of Parkinson’s disease. Today there are more alternative treatment choices for people living with PD. Some recently published studies provide some guidance for an active and informative conversation between the treating clinician and the person living with PD.

One such study published earlier this year, included 58 people living with PD. The study evaluated their preferences of three device-based treatments. The choices were subthalamic nucleus DBS, continuous subcutaneous apomorphine influsion, or levodopa-carbidopa intestinal gel infusion. Each treatment was described and demonstrated. Of the 58 participants, 23 identified DBS as their top preference and the same amount chose their top preference as continuous subcutaneous apomorphine infusion. Only 1 preferred the levodopa-carbidopa intestinal gel infusion. Nearly 23% of the respondents preferred to retain their oral medication routine. Overall, the study demonstrates that people living with PD have differing preferences for device-based treatments and having a choice is important [vii].

On a larger scale, an international team of researchers conducted a survey of 44 movement disorder clinical specialists regarding the similar device-based choices as the previous community study. In this study, they focused on device-based therapies for those living with advanced stages of PD. The study sought to elicit the real-world attitudes of clinicians. Among the participants, 57% agreed that there is a lack of clinical guidelines to identify candidates for each therapy. Over three quarters agreed that there will be a higher demand for device-based therapies in the future [viii].

The choices for those living with PD has grown as alternative therapies gain more clinical evidence. Consider the emergence of focused ultrasound (FUS) for the treatment of PD. FUS is an image-guided, non-invasive therapy that has the potential to deliver therapy to deep-brain structures such as the subthalamic nucleus, which is one target for DBS. In one early-stage study, FUS was provided to 27 of the total 40 participants. Others received sham procedures. The treatment group had a significant improvement of their MDS_UPDRS-3 (Movement Disorder Society-Unified Parkinson’s Disease Rating Scale) score over the control group. However, there were some adverse events associated with the treatment group including dyskinesia, weakness on the treated side, as well as speech and gait disturbances. As a new treatment, further studies are needed to address these adverse events, but this is a potential non-invasive PD treatment for movement disorders related to PD. The study sponsor was Insightec [iv].

Although there are hurdles to overcome, FUS may be a cost-effective treatment when compared to DBS or even radiofrequency ablation (RF). In an overview study of cost-effectiveness of bilateral and unilateral DBS as well as bilateral and unilateral RF. Over a 22-month period, bilateral DBS was identified as the most cost-effective treatment for movement disorders related to PD. The study sets bilateral DBS as the benchmark for cost-effectiveness over a two to five year period. FUS as a incision-less therapy could be a comparable option from a treatment and cost perspective [x].

Wearables as an option

On the topic of cost-effectiveness, wearable neuromodulation technologies are emerging as a viable option to control tremors. Consider Cala Health, their first product, Cala Trio, is a wrist-worn device with stimulating electrodes targeting the radial and median nerves with a counter-electrode on the posterior surface of the wrist. Baked into the device is an individualized calibration method for frequency and amplitude settings using kinematic data with machine learning. The mechanism of action is believed to be the peripheral nerve stimulation of the central tremor network in the brain including the sensorimotor cortex and the ventral intermediate nucleus of the thalamus. The result is a suppression of tremors in the treated hand. The device is currently available in selected regions of the U.S. The device is approved for the treatment of essential tremor and clinical trials are underway for those living with PD.

Another wearable technology under development is from Encora Therapeutics. The device uses artifical intelligence to sense tremor severity in real-time. In response to the sensed tremors, the device delivers an adaptable vibro-tactile stimulus on the wrist to reduce tremors and stiffness. Along with the stimulation, the device allows for monitoring of disease progression via the user interface. The two prior mentioned wearable devices address upper extremity tremors. The ALLEVX device from Allevion Therapeutics can address upper and lower extremity tremors. It may be worn on the wrist or ankle. The device also has an adaptable therapeutic treatment with the ability to adjust the stimualtion in real-time. The Encora and Allevion devices are both curently under investigation.

One other wearable device under investigation is a small non-invasive device worn on the body to deliver vibratory stimulation for the treatment of movement symptoms related to PD. The connected device provides responsive stimulation and works in conjunctions with a smartphone app to set medication alerts, customize stimulation, and to track disease symptoms. The CUE1 device is under investigation for commercialization by Charco Neurotech in the UK.

Other non-invasive neurotech devices such as repetitive therapy robotics, anti-gravity treadmills and vibration therapies are also options for people living with Parkinson’s disease to manage their symptoms and the progession of the disease.

Resources

The devices mentioned in this feature are available in the free directory on the Neurotech Network Parkinson’s Disease Information page. You will find a listing of the devices mentioned here, links to device sites and more. The content for this article was provided by Neurotech Network. Help us support these free resources with a donation.

References:

[i]GBD 2016 Parkinson’s Disease Collaborators. Global, regional, and national burden of Parkinson’s disease, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2018 Nov;17(11):939–953. doi: 10.1016/S1474–4422(18)30295–3. Epub 2018 Oct 1. PMID: 30287051; PMCID: PMC6191528.

[ii] Hausdorff JM. Gait dynamics in Parkinson’s disease: common and distinct behavior among stride length, gait variability, and fractal-like scaling. Chaos. 2009 Jun;19(2):026113. doi: 10.1063/1.3147408. PMID: 19566273; PMCID: PMC2719464.

[iii]Molina R, Hass CJ, Cernera S, Sowalsky K, Schmitt AC, Roper JA, Martinez-Ramirez D, Opri E, Hess CW, Eisinger RS, Foote KD, Gunduz A, Okun MS. Closed-Loop Deep Brain Stimulation to Treat Medication-Refractory Freezing of Gait in Parkinson’s Disease. Front Hum Neurosci. 2021 Mar 1;15:633655. doi: 10.3389/fnhum.2021.633655. PMID: 33732122; PMCID: PMC7959768.

[iv] Gilbert F, Lancelot M. Incoming ethical issues for deep brain stimulation: when long-term treatment leads to a ‘new form of the disease’. J Med Ethics. 2021 Jan;47(1):20–25. doi: 10.1136/medethics-2019–106052. Epub 2020 May 14. PMID: 32409626.

[v]Stoker V, Krack P, Tonder L, Barnett G, Durand-Zaleski I, Schnitzler A, Houeto JL, Timmermann L, Rau J, Schade-Brittinger C, Vidailhet M, Deuschl G; EARLYSTIM Study Group. Deep Brain Stimulation Impact on Social and Occupational Functioning in Parkinson’s Disease with Early Motor Complications. Mov Disord Clin Pract. 2020 Aug 3;7(6):672–680. doi: 10.1002/mdc3.13015. PMID: 32775513; PMCID: PMC7396868.

[vi] Das S, Matias CM, Ramesh S, Velagapudi L, Barbera JP, Katz S, Baldassari MP, Rasool M, Kremens D, Ratliff J, Liang TW, Wu C. Capturing Initial Understanding and Impressions of Surgical Therapy for Parkinson’s Disease. Front Neurol. 2021 Mar 4;12:605959. doi: 10.3389/fneur.2021.605959. PMID: 33746873; PMCID: PMC7970030.

[vii]Aydemir ST, Kumcu MK, Ulukan Ç, Bakirarar B, Akbostancı MC. Patient preference of device-based treatment of Parkinson’s disease. Int J Neurosci. 2021 Jan 5:1–5. doi: 10.1080/00207454.2020.1853723. Epub ahead of print. PMID: 33208012.

[viii] Marsili L, Bologna M, Miyasaki JM, Colosimo C. Device-aided therapies for advanced Parkinson disease: insights from an international survey. Neurol Sci. 2021 Feb 6. doi: 10.1007/s10072–021–05106–4. Epub ahead of print. PMID: 33550525.

[iv] Martínez-Fernández R, Máñez-Miró JU, Rodríguez-Rojas R, Del Álamo M, Shah BB, Hernández-Fernández F, Pineda-Pardo JA, Monje MHG, Fernández-Rodríguez B, Sperling SA, Mata-Marín D, Guida P, Alonso-Frech F, Obeso I, Gasca-Salas C, Vela-Desojo L, Elias WJ, Obeso JA. Randomized Trial of Focused Ultrasound Subthalamotomy for Parkinson’s Disease. N Engl J Med. 2020 Dec 24;383(26):2501–2513. doi: 10.1056/NEJMoa2016311. PMID: 33369354.

[x] Mahajan UV, Ravikumar VK, Kumar KK, Ku S, Ojukwu DI, Kilbane C, Ghanouni P, Rosenow JM, Stein SC, Halpern CH. Bilateral Deep Brain Stimulation is the Procedure to Beat for Advanced Parkinson Disease: A Meta-Analytic, Cost-Effective Threshold Analysis for Focused Ultrasound. Neurosurgery. 2021 Feb 16;88(3):487–496. doi: 10.1093/neuros/nyaa485. PMID: 33295629.

Get the Medium app

A button that says 'Download on the App Store', and if clicked it will lead you to the iOS App store
A button that says 'Get it on, Google Play', and if clicked it will lead you to the Google Play store