Episode 97: Understanding Bradykinesia and Dyskinesia
People with Parkinson’s disease (PD) may experience two seemingly contradictory movement problems. One, bradykinesia, is slowness of movement and is a cardinal symptom of the disease. For a diagnosis of PD, one must have bradykinesia plus either tremor or rigidity. Bradykinesia may appear as a reduction in automatic movements such as blinking or swinging of arms while walking, or it may manifest as trouble initiating intentional movements or just slowness of actions. The second movement problem is dyskinesia, in which people have involuntary, erratic, writhing movements. They can be slow and fluid or rapid and jerking. They are a complication of some Parkinson’s medications and not a symptom of the disease itself. Sometimes people have to decide on their medication dosage and timing whether they would rather be “on” with some dyskinesia or “off” and unable to move well.
In this podcast episode, neurologist Dr. Benjamin Walter delves into bradykinesia and dyskinesia. He is the head of the Section of Movement Disorders and medical director for deep brain stimulation at Cleveland Clinic in Ohio, a Parkinson’s Foundation Center of Excellence. He describes how bradykinesia and dyskinesia can affect people’s lives, what people can do for themselves to alleviate the discomfort, how they can work with their neurologist to minimize the disorders, and what is in development to help.
Dr. Benjamin Walter is the head of the Section of Movement Disorders and medical director for deep brain stimulation at Cleveland Clinic in Ohio, a Parkinson’s Foundation Center of Excellence. Prior to this role, he held the Penni and Stephen Weinberg Chair in Brain Health at University Hospitals and was an associate professor of neurology and biomedical engineering at Case Western Reserve University School of Medicine.
He is board-certified in neurology. Special interests include DBS, dystonia, functional magnetic resonance imaging (MRI), intrathecal baclofen, the mechanism of effect of DBS, movement disorders, Parkinson’s disease and tremors.
He earned his medical degree from MCP-Hahnemann School of Medicine in Philadelphia. He completed his internship in internal medicine and residency in neurology at Emory University Hospital, as well as fellowship training in movement disorders with an emphasis on intraoperative mapping and deep brain stimulation.
In his research laboratory, Dr. Walter uses functional MRI to study mechanisms underlying changes in Parkinson’s disease and dystonia, participating in several projects funded by the National Institutes of Health (NIH). He is currently an investigator on an NIH-funded project exploring intracortical control of arm and hand function restored by functional electrical stimulation in people with spinal cord injury (Brain Gate). He has also served as an investigator on the Enhanced Exercise Study for Patients with Parkinson’s Disease (EXCEED) study of how exercise and education affects people with Parkinson’s disease and depression, as well as on an NIH-funded project to develop an “intelligent” bicycle for rehabilitation in Parkinson’s patients.
Dr. Walter is the author of more than 20 articles in peer-reviewed medical journals, as well as five book chapters. He has presented posters and abstracts at more than 20 international and national peer-reviewed medical conferences.
In addition, Dr. Walter has served as an invited lecturer/instructor at national and international medical education conferences and colloquia. He is grant reviewer for the NIH and the American Association for the Advancement of Science and also reviews manuscripts for several prominent medical journals. He is a member of the Organization for Human Brain Mapping, Society for Neuroscience, American Academy of Neurology and the Movement Disorder Society.
Episode 137: CEO John Lehr Offers Broad Insight into the Parkinson's Foundation
Past podcasts have given glimpses into the broad range of programs and initiatives that the Parkinson’s Foundation has developed and supports. But to give a better understanding of the Foundation’s mission, its operation, reach, and funding, we spoke with John Lehr, its president and CEO. He discussed the reasons for the merger of the National Parkinson Foundation and the Parkinson’s Disease Foundation to form today’s Parkinson’s Foundation, what the new organization has accomplished, and its plans for the future.
Released: September 20, 2022
John L. Lehr leads the Parkinson's Foundation as president and chief executive officer. John guides the overall Foundation’s strategy of mission programs and resources that make life better for people with Parkinson’s. He works to expand the Foundation’s reach, research initiatives and presence, while working to improve health equity among the Parkinson’s community and the underserved. He ensures that all Foundation programs and resources aim to improve care and advance research toward a cure.
Adverse effects, often called side effects, are a common phenomenon that accompanies the use of many drugs, including ones used to treat the symptoms of Parkinson’s disease (PD). Any treatment is a balance between the desired effects of a drug and undesirable ones, so how to best ease symptoms while making the treatment tolerable. Specific to classes of drugs used for PD, some of the side effects may be drowsiness, insomnia, light headedness, hallucinations, cognitive impairment, swelling of the legs, dry mouth, weight gain, compulsive behavior, and others. These are just possibilities, and a good working relationship with a PD health care team can help avoid many of them. Beyond the PD team, keeping other health care providers informed is advisable since drug interactions can occur, so all practitioners (including dentists) should be aware of all medications that a person is taking, prescription, over-the-counter and even supplements.
In this podcast episode, neurologist Dr. Irene Richard of the University of Rochester Medical Center discusses several of the various drugs and drug classes used to treat the symptoms of PD in relation to the adverse effects that can accompany them. She offers insights into several ways to avoid or minimize adverse effects of drug therapy, what clinicians should tell people starting a new drug, and what people should ask as well as be aware of and report back.
Released: December 29, 2020
Dr. Irene H. Richard is Professor of Neurology with a secondary appointment in Psychiatry at the University of Rochester in Rochester, NY. After graduating from Cornell University in 1987 and receiving her MD from the Yale University School of Medicine in1991, Dr. Richard completed neurology residency at the University of Rochester in 1995, followed by NIH-funded fellowship training in Movement Disorders and Experimental Therapeutics in 1997. She joined the faculty of the University of Rochester in 1997. Dr. Richard provides neurological care for patients with Parkinson’s disease and related conditions and her clinical research program focuses on the psychiatric aspects of these illnesses. More recently, with support from a PF community grant, she has also been working with her team on efforts to optimize hospitalization for patients with PD. She is the author of numerous scientific articles, editorials and book chapters and has been the recipient of career development awards and research grants, including one from NIH to lead a multi-center clinical trial evaluating the treatment of depression in PD. Dr. Richard is Director of the University of Rochester’s Movement Disorders Fellowship Program, LBDA Research Center of Excellence, and Parkinson Foundation Center of Excellence.
Episode 134: Meet the Researcher: Disparities in PD Care
As with many medical conditions, people with Parkinson’s disease (PD) may experience disparities in access to care, in diagnosis, treatments, and ancillary care. These disparities may be based on age, gender, race, financial situation, language barriers, and geographic location, among other factors. Dr. Lynda Nwabuobi, now a movement disorders specialist at New York-Presbyterian/Weill Cornell Parkinson’s Disease and Movement Disorders Institute in New York City, received her specialized training at Columbia University, supported by a Parkinson’s Foundation Movement Disorders Fellowship.
During her training, she noticed that women with PD who were home bound were more likely than men to be alone and to have less access to a neurologist. She also recognized disparities in the care between the majority white population of people with PD seen at the main hospital clinic of New York University (NYU) compared to the more racially diverse, multicultural community of people seen at NYU’s public Bellevue Hospital nearby – even though they were being treated by the same doctor. In this podcast episode, she describes how she acted on her passion of “creating access to better care to marginalized communities and bring more diversity to the clinic.” Rather than waiting for the community to come to the health care setting, she reached out to them on their turf — at a farmers’ market.
Released: August 9, 2022
Dr. Lynda Nwabuobi is an Assistant Professor of Clinical Neurology at New York Presbyterian/Weill Cornell Medical College, specializing in Parkinson’s Disease and Movement Disorders. She diagnoses and treats individuals with Parkinson’s disease, tremors, and other neurological diseases with the goal of delivering compassionate and individualized care using a holistic and multidisciplinary approach. In addition to her clinical work, Dr. Nwabuobi has interests in health disparities research, teaching, advocacy, and community engagement/outreach. She has published several articles in peer-reviewed journals and has presented her work at national and international conferences. She is actively involved in educating underserved communities about Parkinson’s disease with the goal of improving access to care.
Meet a Researcher Working to Make Adaptive DBS More Effective
🧠 What will you learn in this article?
This article highlights ongoing research aimed at improving the effectiveness of adaptive deep brain stimulation. It discusses:
The definition of adaptive DBS (aDBS).
Adaptive deep brain stimulation and how it can alleviate Parkinson’s symptoms.
Research into whether “entrained-gamma” signals may make adaptive deep brain stimulation more effective than the “beta” signals currently used in the treatment.
How this research could improve the lives of people with Parkinson’s.
Over time, Parkinson’s disease (PD) medications can begin to lose their effectiveness. When this happens, deep brain stimulation (DBS) can be a promising treatment option for certain candidates. For DBS, electrodes are implanted into the brain that deliver controlled electrical stimulation that counteracts PD symptoms.
Most DBS systems are designed to deliver consistent stimulation based on settings set and updated by physicians. However, a newer version called adaptive DBS (aDBS), recently approved by the U.S. Food and Drug Administration (FDA) for clinical use, monitors brain signals associated with PD symptoms in real time and adjusts stimulation automatically. This ability to auto-adjust stimulation has the potential to enhance DBS efficiency and minimize side effects, improving quality of life for those that use it.
Adaptive DBS (aDBS) monitors brain signals associated with Parkinson’s symptoms in real time and automatically adjusts DBS stimulation.
Lauren Hammer, MD, PhD, recipient of a Parkinson’s Foundation Stanley Fahn Junior Faculty Award, is working to make aDBS even more effective by determining which types of brain signals offer the best information on how to adjust stimulation in response to symptoms. Current aDBS technology monitors low-frequency brain waves called “beta” signals, but Dr. Hammer believes that higher frequency “entrained-gamma” signals may be better for predicting and controlling PD symptoms.
“This research aims to advance deep brain stimulation for Parkinson’s disease by identifying the most effective neural signal to guide adaptive DBS,” said Dr. Hammer. “Results could support expanding the set of neural signals used for clinical aDBS, enabling more effective and personalized treatment.”
From her lab at the University of Pennsylvania, a Parkinson’s Foundation Center of Excellence, Dr. Hammer will first run an in-laboratory assessment where people with PD perform various movement tasks while their brain signals are monitored. This will provide data as to which type of signal — beta or entrained-gamma — offers a more accurate reflection for when PD symptoms like involuntary movements are occurring.
Dr. Hammer will then take a small group of people with DBS for PD and upgrade them to aDBS for an at-home study. After participants are programmed for aDBS stimulation using both beta signals and entrained-gamma signals, they will switch weekly between these settings, recording how well their symptoms are controlled at home.
At the end of the trial, Dr. Hammer and her team will have data to suggest which signal type guided the best aDBS experience for different types of people with PD.
“I’m deeply grateful to the Parkinson's Foundation for investing in early-career scientists and accelerating progress toward better care and a cure.” – Dr. Hammer
“Receiving this Parkinson’s Foundation award is an incredible honor and an important milestone in my journey to improve the lives of people with Parkinson’s disease,” said Dr. Hammer. “As a new faculty member starting my own laboratory, this support comes at a critical time — helping me build the foundation for a research program focused on developing next-generation deep brain stimulation therapies. Funding at this early stage is vital to turning promising ideas into impactful treatments, and this award will help bridge the gap between training and long-term research support.”
Investigating New Ways to Address Posture Impairment in Parkinson’s
A common symptom of Parkinson’s disease (PD) is impaired posture. Unfortunately, this symptom is resistant to standard dopamine replacement therapies, and not much is known about the neurological mechanisms that lead to it. Left unchecked, posture impairment can lead to serious falls and other injuries for people with PD.
Colum MacKinnon, PhD, recipient of a Parkinson’s Foundation Impact Award, suspects that PD affects brainstem neurons responsible for sending posture-related signals to the muscles of the legs and feet. Investigating this potential mechanism behind PD-related posture impairment may contribute to future treatments that could alleviate this debilitating symptom.
“If successful, this work will be the first to demonstrate that brainstem pathways that control muscle firing properties are altered in people with PD and are associated with postural impairment.” – Dr. MacKinnon
Dr. MacKinnon, with the help of his coinvestigators Dr. Laura McPherson, PT, DPT, PhD, and Dr. Daniel Free, PhD, will enroll people with and without PD, recording and analyzing their posture and gait (walking manner). He will also use a device to measure muscle activity activity as they point and flex their feet, capturing nerve signals important for balance and posture.
From this initial data collection, Dr. MacKinnon expects to see reduced postural muscle activity that is controlled by descending brainstem systems in people with PD, and this reduction will correlate with impaired posture and walking ability.
Next, Dr. MacKinnon will use a noninvasive vagus nerve stimulation device, commonly used to treat migraines and cluster headaches, to stimulate neurons within the brainstem associated with postural control. If his hypothesis is correct, this stimulation will temporarily improve the posture and balance of those with PD as the signals to the ankle muscles are restored. These studies will provide valuable direction for future research and therapeutic development of PD-associated posture impairment, which could significantly improve quality of life for people with PD.
“This award provides the unique opportunity to explore the potential contributions of non-dopaminergic pathways to the abnormal muscle activation patterns observed in people with PD, and to conduct exploratory experiments to test the efficacy of using vagus nerve stimulation to upregulate these pathways, improve muscle activation, gait and postural control,” said Dr. MacKinnon.
La medicación desempeña un papel fundamental en el tratamiento de la enfermedad de Parkinson (EP), pero es sólo una parte de un plan de cuidados más amplio.
El siguiente artículo se basa en una Charla con Expertos - Expert Briefing de la Parkinson's Foundation donde el Dr. Danny Bega explora cómo encajan los medicamentos en el cuidado integral y holístico del Parkinson. El Dr. Bega tiene una maestría en Ciencias, es profesor adjunto de Neurología, director médico y director del programa de residencia en Neurología del Centro de la Enfermedad de Parkinson y Trastornos del Movimiento de la Northwestern University Feinberg School of Medicine, un Centro de Excelencia de la Parkinson’s Foundation. También es director de los programas de las enfermedades de Huntington y Wilson en Northwestern.
Comprender la conexión entre la dopamina y el Parkinson
El Parkinson es un trastorno progresivo relacionado con la disminución de los niveles de dopamina, una sustancia química cerebral que influye en el movimiento, la memoria y muchos otros procesos vitales del organismo. Otras sustancias químicas del cerebro, como la norepinefrina y la serotonina, también pueden verse afectadas en la enfermedad de Parkinson e influir en los síntomas.
A medida que avanza el Parkinson, el número de células cerebrales que producen dopamina sigue disminuyendo y las células restantes luchan por almacenar y liberarla. Esto provoca lentitud de movimientos, temblores, rigidez y otros síntomas motores. También puede causar diversos síntomas no motores, como estreñimiento, pérdida del olfato y cambios en el pensamiento.
Manejo del Parkinson’s
El Parkinson es una enfermedad compleja. No existe un tratamiento estándar. Sin embargo, los medicamentos —junto con el ejercicio, la atención integral, una dieta nutritiva y prácticas de atención plena— pueden controlar los síntomas del Parkinson y ayudarle a vivir bien.
Establecer una rutina de ejercicio poco después del diagnóstico puede ayudar a ralentizar la progresión de la enfermedad y mejorar el movimiento, la fuerza, el equilibrio y el estado de ánimo. También puede ayudarle a dormir mejor. Mantenerse social e interactuar puede reducir la sensación de soledad.
Su equipo de atención es igualmente importante. Busque profesionales médicos expertos en Parkinson, incluyendo un neurólogo, un terapeuta del habla y el lenguaje, un fisioterapeuta y un terapeuta ocupacional, un trabajador social y otros profesionales de la salud, para que le ayuden a controlar los síntomas de la EP. No deje de acudir a las revisiones periódicas.
El papel de los medicamentos
La mayoría de los medicamentos para el Parkinson mejoran los síntomas aumentando la dopamina en el cerebro o actuando como la dopamina. La levodopa es el fármaco más eficaz para tratar los síntomas del Parkinson. En el transcurso del Parkinson, la mayoría de las personas tomarán levodopa en algún momento.
La ansiedad y la depresión también pueden ser frecuentes en el Parkinson y afectar al bienestar incluso más que los síntomas motores. Tratar estos síntomas mediante una combinación de medicamentos, como un ISRS, un IRSN o la mirtazapina, —un antidepresivo tricíclico—, junto con terapia, control del estrés y mantener la actividad física, puede reducir la discapacidad significativamente.
Las personas recién diagnosticadas de Parkinson a menudo se preguntan cuándo deben empezar a tomar la medicación. Los estudios demuestran que esperar no tiene beneficios. La mayoría de los médicos concuerdan en que debe empezar a tomar la medicación cuando los síntomas se vuelvan molestos.
Dado que no cada persona experimenta la EP de forma única, los tratamientos varían de una persona a otra, al igual que el ritmo de progresión. Sin embargo, conocer los estadios típicos del Parkinson puede ayudarle a anticiparse a los cambios:
En los primeros cinco años después del diagnóstico, es posible que los síntomas no afecten su vida diaria significativamente. Su médico podría recomendarle un ensayo clínico. La participación en la investigación del Parkinson podría darle acceso temprano a nuevos tratamientos, mejorar la atención y sentar las bases para una cura.
En un plazo de uno a diez años, conforme los síntomas empiezan a interferir con las actividades, la mayoría de las personas con Parkinson pueden esperar una respuesta duradera y constante a la medicación.
Entre cinco y 20 años después del diagnóstico, al cerebro le resulta cada vez más difícil conservar dopamina. La respuesta de su cuerpo a la levodopa puede volverse más corta y menos eficaz. Esto puede provocar fluctuaciones motoras: periodos en "on", cuando la medicación funciona bien, y periodos en "off", cuando la medicación deja de hacer efecto y los síntomas reaparecen. Es importante trabajar de cerca con su médico para ajustar el tratamiento y encontrar lo que mejor se adapte a usted.
Después de 10 o más años de vivir con Parkinson, las personas pueden experimentar problemas más importantes. Algunas personas pueden desarrollar importantes problemas de memoria y pensamiento. Problemas de equilibrio, caídas y congelamiento (la incapacidad temporal para moverse) también puede volverse un problema. Su médico puede hablarle de ajustes de la medicación o terapias farmacológicas o mandarlo a ver a un profesional médico adecuado para sus necesidades, que puede ser un neuropsicólogo, un psiquiatra, un terapeuta del habla y el lenguaje o un terapeuta ocupacional.
Tipos de medicamentos utilizados en el Parkinson
Es frecuente que las personas con Parkinson tomen una variedad de medicamentos, en distintas dosis y momentos del día, para manejar los síntomas. Esto puede incluir:
Agonistas de la dopamina: al principio, los fármacos que estimulan la dopamina en el cerebro, como el pramipexol, el ropinirol y la rotigotina, a menudo pueden tratar los síntomas motores del Parkinson. Los agonistas de la dopamina presentan menos riesgo de discinesias, movimientos erráticos involuntarios que suelen comenzar tras unos años de tratamiento con levodopa.
Los efectos secundarios pueden incluir náuseas, mareos, somnolencia, confusión y trastornos del control de los impulsos, como compras compulsivas, juegos de azar, comer en exceso y los impulsos sexuales. Los estudios muestran que un 28% de las personas con Parkinson dejan de tomar agonistas de la dopamina debido a los efectos secundarios, mientras que un 40% necesita añadir otra medicación en un plazo de dos años.
Levodopa: la levodopa, el fármaco más eficaz para los síntomas motores del Parkinson, sustituye a la dopamina en el cerebro. Suele administrarse en combinación con el fármaco carbidopa para reducir las náuseas, un efecto secundario frecuente. Tomar levodopa con las comidas también puede reducir las náuseas, pero las proteínas pueden interferir en la eficacia del fármaco. Alrededor de un 2% de las personas dejan de tomar levodopa debido a los efectos secundarios, mientras que un 15% necesita añadir otra medicación a los dos años.
Las discinesias, también relacionadas con la levodopa, pueden controlarse a menudo mediante un ajuste de la dosis o mediante tratamiento directo, utilizando un medicamento llamado amantadina. Funciona bloqueando el NMDA, una sustancia química que provoca movimientos extras. La amantadina de liberación inmediata también se utiliza a veces sola para los síntomas motores del Parkinson. Existe un mayor riesgo de confusión y alucinaciones con el uso de amantadina en personas de más de 75 años. También puede asociarse a hinchazón de piernas, alteraciones de la piel y otros efectos secundarios.
Anticolinérgicos:Los medicamentos trihexifenidilo y benztropina se utilizan a veces para mejorar el temblor o las distonías (calambres dolorosos y sostenidos). Actúan bloqueando la acetilcolina, una sustancia química del cerebro relacionada con el movimiento. Sin embargo, su uso debe evitarse en personas de 70 años o más debido al riesgo de confusión y alucinaciones. Los anticolinérgicos también pueden asociarse a visión borrosa, sequedad de boca, estreñimiento y retención urinaria.
Algunos de los medicamentos que su médico podría considerar para mejorar los efectos de la levodopa son:
Inhibidores de la MAO-B: los inhibidores de la monoaminooxidasa B rasagilina, selegilina y safinamida ponen más dopamina a disposición del cerebro. Estos medicamentos pueden utilizarse solos o en combinación con la levodopa para aumentar su eficacia. Los inhibidores de la MAO-B suelen tolerarse bien, pero un 70% de las personas que los toman solos para el Parkinson necesitarán añadir otra medicación a los dosaños.
Inhibidores de la COMT: medicamentos como la entacapona y la opicapona aumentan la levodopa disponible en el cerebro al bloquear la enzima catecol-O-metil transferasa.
Antagonista del receptor A2A: la istradefilina, un antagonista de la adenosina A2A, bloquea la adenosina en los receptores A2A del cerebro para reducir el tiempo en "off" de la levodopa.
La levodopa inhaladase utiliza a menudo con la levodopa, según sea necesario, para el tiempo en "off" repentino. La apomorfina inyectable también puede utilizarse a demanda, para el alivio en tiempos en "off". Ambos medicamentos pueden aumentar el riesgo de discinesias.
Es importante trabajar con su médico para encontrar el equilibrio adecuado para usted. Su médico puede aumentar o disminuir su dosis de levodopa con base en sus síntomas. Por ejemplo, el temblor, la rigidez o los problemas de movilidad podrían beneficiarse de un aumento de la levodopa. Sin embargo, las alucinaciones, la confusión y la baja presión arterial podrían mejorar con una disminución de la levodopa.
También existen estrategias y medicamentos para controlar el babeo, el goteo nasal, los problemas de sueño, los problemas intestinales, los cambios en el pensamiento y otros desafíos del Parkinson.
¿Qué pasa si no funciona la levodopa?
Si está tomando levodopa pero no obtiene beneficios, hable con su médico. Estas son algunas preguntas que puede hacer:
¿El síntoma que le molesta no responde bien a la levodopa? ¿Podría estar relacionado con otro problema de salud?
¿Puede haber algo que esté interfiriendo en la absorción de la medicación? Algunas personas experimentan menos beneficios cuando toman levodopa con una comida alta en proteínas.
También es importante discutir si es necesario ajustar la dosis. Por ejemplo, los efectos del Sinemet, una forma de levodopa, sólo duran poco tiempo: a los 90 minutos, la mitad ha desaparecido. Su médico puede ajustar el horario y la dosis de levodopa, utilizar una formulación de acción más prolongada o recomendar tomar la medicación 30 minutos antes o 60 minutos después de comer.
Terapias avanzadas
Si se vuelve difícil controlar las fluctuaciones motoras ajustando la medicación oral, existen otras opciones para mejorar la absorción de la medicación y reducir el tiempo en "off":
La terapia con Duopa suministra carbidopa-levodopa en gel directamente al intestino a través de un tubo colocado quirúrgicamente.
La terapia con foscarbidopa y foslevodopa (Vyalev) utiliza una bomba para administrar de forma constante una forma de levodopa bajo la piel a través de un pequeño tubo llamado cánula. Se utiliza una aguja para colocar la cánula.
La terapia continua con apomorfina (Onapgo) utiliza una bomba para administrar apomorfina de forma continua a través de una fina aguja colocada bajo la piel.
Estos medicamentos requieren ajustes en el estilo de vida, instrucción para su uso y un compromiso con el buen cuidado de la piel para reducir el riesgo de irritación e infecciones.
Otras opciones además de la medicación
En ocasiones, los síntomas de Parkinson más avanzados pueden beneficiarse de otras estrategias de tratamiento, como la estimulación cerebral profunda (ECP, o DBS, por sus siglas en inglés), que consiste en implantar quirúrgicamente un generador de impulsos eléctricos conectado a electrodos colocados en el cerebro para tratar los síntomas motores del Parkinson y algunos síntomas no motores.
La ECP podría ser considerada para alguien que:
vive con la enfermedad de Parkinson clásica
tiene síntomas que responden a la levodopa
experimenta frecuentes fluctuaciones motoras y temblores, a pesar de una dosificación constante de la medicación
tiene discinesias molestas
Tras la ECP, muchas personas pueden reducir su medicación y seguir experimentando una reducción de los síntomas de la EP. La reducción de la dosis de medicamento puede llevar a menos discinesias.
El ultrasonido focalizado, una terapia no invasiva, no requiere una incisión quirúrgica. Durante el procedimiento, se dirigen ondas sonoras de alta frecuencia a una zona específica del cerebro relacionada con el temblor para aliviar el temblor de la enfermedad de Parkinson. A diferencia de la terapia de ECP, que es ajustable y reversible, los cambios por ultrasonido focalizado son permanentes.
Si tiene preguntas acerca de las opciones de tratamiento de la EP, comuníquese con nuestra Línea de Ayuda al 1-800-4PD-INFO (473-4636) opción 3 para español o en Helpline@Parkinson.org.
Aprenda más
Explore nuestros recursos acerca de medicamentos para tratar los síntomas del Parkinson:
Designing Nanobodies that Stabilize Dysfunctional Proteins in Parkinson’s
The most common genetic risk factor associated with Parkinson’s disease (PD) lies in the GBA1 gene. Research from the Parkinson’s Foundation genetics study, PD GENEration, has found the GBA1 gene is present in 5-10% of people with the disease. GBA1 provides the instructions to make a protein called glucocerebrosidase (GCase), which plays an important role in the waste recycling compartment of the cell, known as lysosomes. Variants linked to PD produce unstable or less active versions of GCase. As a result, cells lose part of their cleanup ability, leading to a buildup of harmful proteins such as alpha-synuclein.
Wim Versées, PhD, recipient of a Parkinson’s Foundation Impact Award, has discovered a set of small proteins called “nanobodies” that attach to and stabilize these fragile forms of GCase, restoring their functionality in cells where they are needed most.
Most previous research tried to stabilize GCase using small molecule “chaperones”. These compounds could bind and protect the protein but are often attached to the protein’s active site — the very region needed for its normal function, blocking its activity. The nanobodies, by contrast, stabilize GCase by binding to a previously unexplored site far away from the active site, preserving its natural role.
Think of mutant GCase as a fragile vase you want delivered safely to your home. One way to protect it during shipping is to fill it with solid material. That will prevent it from breaking, but once it arrives you can no longer use it to hold flowers. This is what happens when molecules bind the active site. Nanobodies, instead, act by binding or wrapping on the outside of the vase. They keep it intact while still allowing it to hold flowers.
Supported by the Parkinson’s Foundation Impact Award, Dr. Versées, and his lab at the Flanders Institute for Biotechnology in Belgium, will run a battery of biochemical experiments to hone the design of GCase-stabilizing nanobodies. First, he will use state-of-the-art molecular imaging techniques to see exactly where these nanobodies stick to GCase and how it affects the protein. This information will help Dr. Versées and his team identify which set of nanobodies are the best suited for clinical use and how he can further improve their effectiveness.
Collaborating with Steven Ballet, PhD, at Vrije Universiteit Brussel, they will also design so-called “peptidomimetics” that are inspired by the nanobodies and have similar GCase-stabilizing features. Since these are much smaller, they can be more easily delivered to the correct cells in the brain, acting as prototypes for future therapeutics.
Finally, working with Nicoletta Plotegher, PhD, at the University of Padova in Italy, Dr. Versées will test the effectiveness of these nanobodies and peptidomimetics in PD-simulated cells in the lab. Monitoring to what extent the mutant GCase proteins are stabilized and activated with these treatments will validate their potential for future research and their potential as a future treatment.
Excited by this support, Dr. Versées said “Receiving this award from the Parkinson’s Foundation is both a personal honor and a meaningful endorsement of our research. If successful, this strategy could lead to a new class of molecular chaperones that more effectively target the underlying molecular causes of Parkinson’s, opening new therapeutic avenues for people living with GBA1-associated PD.”
Investigating Which Brain Signals Best Guide Adaptive Deep Brain Stimulation
Deep brain stimulation (DBS) is a promising treatment option for those with Parkinson’s disease (PD) when medications begin to lose their effectiveness. For DBS, electrodes are implanted into the brain that deliver controlled electrical stimulation that counteracts the PD symptoms.
Most DBS systems are designed to deliver constant, consistent stimulation based on settings set and updated by physicians during checkups. However, a newer version called adaptive DBS (aDBS), recently approved by the FDA for clinical use, monitors brain signals associated with PD symptoms in real time and adjusts stimulation automatically. This ability to auto-adjust stimulation has the potential to enhance DBS efficiency and minimize side effects, improving quality of life for those that use it.
Lauren Hammer, MD, PhD, recipient of a Parkinson’s Foundation Stanley Fahn Junior Faculty Award, is working to make aDBS even more effective by determining which types of brain signals offer the best information on how to adjust stimulation in response to symptoms. Current aDBS technology monitors low-frequency brain waves called “beta” signals, but Dr. Hammer believes that higher frequency “entrained-gamma” signals may be better for predicting and controlling PD symptoms.
“This research aims to advance deep brain stimulation for Parkinson’s disease by identifying the most effective neural signal to guide adaptive DBS,” said Dr. Hammer.
From her lab at the University of Pennsylvania, a Parkinson’s Foundation Center of Excellence, Dr. Hammer will first run an in-laboratory assessment where people with PD perform various movement tasks while their brain signals are monitored. This will provide data as to which type of signal — beta or entrained-gamma — offers a more accurate reflection for when PD symptoms like involuntary movements are occurring.
Dr. Hammer will then take a small group of people with DBS for their PD and upgrade them to aDBS for an at-home study. After participants are programmed for aDBS stimulation using both beta signals and entrained-gamma signals, they will switch weekly between these settings, recording how well their symptoms are controlled at home.
At the end of the trial, Dr. Hammer and her team will have data to suggest which signal type guided the best aDBS experience for different types of people with PD.
When asked what this support means to her and her research goals, Dr. Hammer said “Receiving this award is an incredible honor and an important milestone in my journey to improve the lives of people with Parkinson’s disease. This research could support expanding the set of neural signals used for clinical aDBS, enabling more effective and personalized treatment.”
Branching Out Toward New Parkinson’s Therapies by Studying the Brainstem
In Parkinson’s disease (PD), specific dopamine-producing neurons in the brain degenerate over time and lead to progressive movement and cognitive symptoms. A multitude of therapeutic research has focused on the impact of losing these neurons on connections within the brain, which has helped develop treatments like dopamine replacement therapy (DRT) and deep brain stimulation (DBS).
While generally effective, these therapies have their limitations and side effects, prompting investigation into alternative treatment strategies. Jared Cregg, PhD, recipient of a Parkinson’s Foundation Stanley Fahn Junior Faculty Award, is exploring how modulating a different area of the brain, the brainstem, could provide new therapeutic potential for those with PD.
The loss of dopamine in PD rewires the circuitry of the brain in several regions critical for movement. Many of these brain areas are highly “plastic,” meaning that they are prone to being rewired, particularly in a disease like PD. However, the circuits within the brainstem produce stable, reflexive motor actions, and Dr. Cregg hopes to leverage the stability of these connections to help restore movement to people with PD.
“This work aims to establish a new framework for treating movement impairments in Parkinson’s disease by shifting focus from traditional targets to the brainstem circuits that naturally govern locomotion.” – Dr. Cregg
From his lab at the University of Wisconsin – Madison, where he is an assistant professor of neuroscience and neurology, Dr. Cregg will first create a biochemical map of two brainstem regions known as the pedunculopontine nucleus (PPN), which regulates movement speed, and the rostral pontine reticular formation (PnO), which regulates turning. This map will then help him to develop tools to selectively target specific neurons in those regions that control these movements in mice.
These tools will enable Dr. Cregg to stimulate these neurons at will. By testing these tools in mice that have Parkinson’s-like symptoms, he can see the potential effects of future therapies that target the brainstem in a similar way. The scientific knowledge gained from these experiments will guide future brainstem-centered PD treatments.
When asked about what this support means to him and his work, Dr. Cregg said “Receiving this award is an incredible honor and a meaningful endorsement of our efforts to chart a new path in Parkinson’s research. By refining these brainstem-based therapies, this work could pave the way for more stable, long-lasting interventions that improve movement in people with PD.”
