In a landmark investment to accelerate the path to a Parkinson’s disease (PD) cure, in 2019, the Parkinson’s Foundation awarded $8 million to establish four elite Parkinson’s Foundation Research Centers. Each one received $2 million over four years.

In this series of articles, we will share the story of each center — their goals, successes, surprises and the future of their PD research. In this article, we check in with the Parkinson’s Foundation Research Center at the Yale School of Medicine.

Research Centers

The Parkinson’s Foundation selected four centers for their groundbreaking potential to transform PD research. Together, they launched a series of innovative, interlinked studies aimed at deepening our understanding of PD and translating discoveries into real-world impact for people living with the disease.

Studies ranged from basic science (understanding the disease or how PD affects the brain) to applied science (solving real-life problems associated with PD) to clinical research in humans or a combination of these.

Before The Award

At first, despite housing many scientists and clinicians with interests in PD, Yale School of Medicine did not have a hub specifically focused on the molecular mechanisms causing the disease.

To fill this gap, in 2005 Yale established the Interdepartmental Program in Cellular Neuroscience, Neurodegeneration and Repair (CNNR), and began recruiting top researchers with diverse expertise and the shared goal of advancing the understanding of neurodegenerative diseases like Parkinson’s. The first recruited was Sreeganga Chandra, PhD, who had prior postdoctoral experience in PD research.

“Dr. Chandra played an important role in seeding and promoting interest in the cell biology of PD at Yale” said Pietro De Camilli, MD, a cellular neurobiologist and one of the two founding directors of the CNNR program.

At the time, Dr. De Camilli had no prior track record in PD research, but he soon discovered that two major proteins he was studying were products of two genes implicated in familial early-onset PD, leading him to realign his work around PD disease mechanisms.

Another investigator associated with the CNNR, Shawn Ferguson, PhD, also had never worked on PD, but was “an expert in the cell biology of lysosomes, a cell compartment whose importance in PD pathogenesis, and more generally in neurodegenerative diseases, was being increasingly recognized,” said Dr. De Camilli.

When the Parkinson’s Foundation announced its call for Research Center proposals, Dr. De Camilli invited colleagues Dr. Chandra and Dr. Ferguson to apply together. The idea of the team was to focus on a theme that had emerged in PD genetics and was relevant to each of their labs’ research: endolysosomal dysfunction.

Toward this aim, the team proposed original and high-impact projects. The Parkinson’s Foundation recognized their potential, awarding them Research Center funding to launch three major studies:

1. Understanding how the defect of a protein called auxilin may cause PD (Dr. Chandra)

2. Investigating the link between PD and lysosomes, the recycling stations of the cell (Dr. Ferguson)

3. Uncovering how dysfunction of lipids (fats)-building blocks of the walls of endolysosomal compartments may cause PD (Dr. De Camilli)

Cellular Processes Underlying PD

At a cellular level, there are two key problems that occur in PD. One is a drop in dopamine.  This is the chemical signal that is used for communication between brain cells called neurons and, in turn, helps the body process movement and moods. The other problem is a buildup of a sticky protein called alpha-synuclein inside neurons.

Both issues are linked to defects in how cells manage their internal transport system.  This is the complex movement of materials and nutrients through the cell’s “endolysosomal system.” The endolysomal system uses an intricate array of small containers called vesicles moving inside a cell to handle export, import, sorting, recycling and disposal functions.

To picture this, imagine each neuron as a small city that is in constant communication with other neurons. Each neuronal city depends on the export and import of shipments of supplies through communication centers with other neuronal cities called “synapses.” Cargo is sorted and loaded into the “vesicles,” shipping containers that carry materials where they are needed.  There are major centers inside cells, called “endosomes,” where all the material is sorted. Some special cargo is imported into cells via locked containers called “clathrin-coated vesicles.” Once inside the city, these containers are “unlocked” by shedding their clathrin coat so their content can be delivered to endosomes.

After deliveries are made, the vesicles are reused to take any waste to the cell’s recycling center, called a “lysosome.” These lysosome recycling centers break down waste with enzymes and acid in compartments safely tucked away from the rest of the cell. In so doing, lysosomes liberate nutrients that can be used to build new cellular components. These processes collectively support the ability of neurons to communicate with each other while also preventing the accumulation of cellular trash (including alpha-synuclein buildup) and ensuring a supply of building materials to maintain neuronal health.

The three main research projects supported by the Research Center Award focus on understanding and fixing problems in these cellular transport and recycling systems — processes that are disrupted in Parkinson’s.

Unlocking the Connections Between Auxilin & PD: Dr. Chandra

Following the release of dopamine from one neuron to another, the vesicle containers used to deliver dopamine to the synapse need to be rebuilt. Neurons rebuild them using clathrin-coated vesicles, the cell's locked shipping containers. To unlock these containers, neurons use a special "key" protein called auxilin, which was the focus of Dr. Chandra’s research.

Mutations that cause auxilin defects are linked to early-onset PD, but how auxilin dysfunction contributes to the disease was poorly understood. Dr. Chandra and her team first characterized mice that lack auxilin to see if they were a good model for PD research.

Dr. Chandra said, "the mice lacking auxilin develop cardinal features of Parkinson’s disease: age-dependent motor deficits that are responsive to L-DOPA, the death of dopaminergic neurons in the substantia nigra, and alpha-synuclein pathology.”

Next, Dr. Chandra discovered that being unable to unlock the clathrin containers also impacted the neuron’s ability to rebuild packages containing dopamine. Imagine this as a cellular traffic jam, where the locked containers get stuck in transit.  This prevents them from bringing in other materials, being unlocked and reused for a new shipment.

The shipment of dopamine, the key signal that declines in PD, was also impacted in this neuronal traffic jam. At the synapses, there were fewer containers for it to be loaded into and released for communication with other neurons. Finding a way to unlock containers and prevent traffic jams would be key to making dopamine more available and improving PD symptoms.

With that in mind, Dr. Chandra collaborated with Dalibor Sames, PhD, at Columbia University to test the effects of a repurposed drug called Ariadne on the auxilin-lacking mice.

They found that this drug had a remarkable impact on restoring balance and mobility in the mice, similar to levodopa. While there is still much more to learn about these drug effects, this collaborative research has brought to light Ariadne as a potential future treatment for people with PD, particularly those with auxilin mutations.

Understanding Links Between Disrupted Disposal of Cellular Waste & PD: Dr. Ferguson

Dr. Ferguson was new to PD research before his Research Center involvement. “This provided an opportunity for me to bring my research focused on the intersection between lysosomes and neurodegenerative diseases into the Parkinson’s field,” said Dr. Ferguson.

Lysosomes, the cell’s recycling centers, are managed by different genes and proteins. Dr. Ferguson hypothesized that the protein LRP10, which has documented mutations linked to familial PD, was a recycling facilitator. After investigating how cells behave when LRP10 is turned off, he and his research team found that LRP10 indeed plays a significant role in facilitating lysosome function.

Following the city metaphor, LRP10 helps navigate delivery containers to lysosomes, bringing in proteins that support lysosomal function. Without LRP10’s help, the cells’ ability to build working recycling centers is disrupted. In PD, when lysosomes don’t break down and recycle waste properly, proteins like alpha-synuclein build up. Alpha-synuclein forms toxic clumps that damage brain cells, leading to tremors, stiffness, and other movement and non-movement symptoms.

Dr. Ferguson and his team also developed mice with genetic mutations of LRP10 and looked at how their brains were affected. They found that the loss of LRP10 impacts a specific type of cell in the brain, called microglia, which protect neurons. Dr. Ferguson also uncovered links between microglia and one of the most well-known PD genes LRRK2, revealing new roles for LRRK2 in regulating lysosomes in microglia that were never known before.

The success and breakthroughs from this project have shifted the focus of Dr. Ferguson’s career to PD.

“This Research Center Award was the gateway for my entry into the Parkinson’s disease field and was thus a catalyst that fueled a much broader Parkinson’s program. I am also committed to recruiting additional colleagues with complementary skills into the PD field to increase our collective chances to make the discoveries necessary to end this disease.” - Dr. Ferguson

Connecting lipid dynamics in the endolysosomal system & PD: Dr. De Camilli

“My interest in PD was sparked by the finding that two proteins studied in our lab were identified by human genetic studies as PD proteins,” said Dr. De Camilli, referring to synaptojanin 1 (Synj1, also known by the name PARK20) and VPS13C (also known as PARK23). Both proteins regulate lipids (fats) - building blocks of the walls of different compartments of the endolysosomal system.

These two proteins function at different steps in the cell’s endolysosomal transport system and link Dr. De Camilli’s research directly to his colleagues: Synj1 is a functional partner with Dr. Chandra’s auxilin at the earliest step (clathrin-coated vesicles), and VPS13C is involved with Dr. Ferguson’s lysosomes (the latest step).

Dr. De Camilli and his team discovered that Synj1 is required to begin the unlocking process of clathrin containers after they are imported by modifying the lipids they are made of. In mice with Synj1 mutations, they observed PD-like symptoms.

Working with Dr. Chandra’s lab, they also found that mice with both auxilin and Synj1 mutations have significantly more issues, highlighting that the two proteins have important, cooperative roles in cells. Ongoing work from both researchers is investigating this overlap further.

Dr. De Camilli’s lab also learned that the protein VPS13C, a lipid transport protein, has an important role in repairing damaged lysosomes. As a lysosome is used heavily in recycling, its walls can begin to break down, threatening to leak toxic enzymes and acids into the cell, VPS13C helps bring the lipids needed to rebuild the walls. Most interestingly, in collaboration with Dr. Ferguson, they found that the PD protein LRRK2 works in tandem with VPS13C in lysosome repair, a new discovery.

Understanding how PD mutations affect neuronal function is crucial in designing new PD treatments.

Dr. De Camilli is now highly committed to continue his studies of PD. “In my own lab, I will continue to expand my research on how mutations in Synj1 and VPS13C result in PD. We are very excited for being part of this new era of PD research.”

Building Collaborations as a Parkinson’s Foundation Research Center

Being a Parkinson’s Foundation Research Center not only supported these three main projects but also inspired the growth of PD research across Yale.

The groundbreaking research of the Yale Research Center team motivated other Yale researchers to explore how their own work could contribute to the understanding of PD. This award's dedicated funding for additional pilot projects allowed those researchers to join the PD field for the first time.  

“We have awarded pilot projects to four principal investigators who had never worked on PD, and three of them have continued to work on this disease and are now involved in long-term collaborations with our groups,” said Dr. De Camilli.

“The momentum and enthusiasm for PD research at Yale led to support from numerous other funders devoted to PD scientific breakthroughs, such as Aligning Science Across Parkinson’s (ASAP), the Michael J. Fox Foundation, the Chan Zuckerberg Initiative, the Bumpus Foundation and the McKnight Foundation,” said Dr. Chandra.

This support led to new academic collaborations and joint publications as well, “connecting us to the PD community at large across different institutions in the US and abroad,” said Dr. De Camilli.

What began as three PD experimental proposals being accepted as a Parkinson’s Foundation Research Center has evolved into Yale becoming a nationally recognized hub for PD research.

“Beyond our individual projects, the Parkinson’s disease research community at Yale has grown dramatically over the past five years,” said Dr. Ferguson.

While the Research Center designation has concluded, its impact on the Yale School of Medicine and the scientists investigating PD remains, moving the institution and the greater PD research world toward future new treatments and, someday, a cure.

Learn More

The Parkinson’s Foundation works to improve care for people with PD and advance research toward a cure. Learn more with these resources:

• Discover how we are working to close gaps in knowledge about PD: Advancing Research

• Learn about and enroll in PD GENEration — a global genetics study that provides genetic testing and counseling at no cost for people with Parkinson’s.

• Explore ways to get involved in the Parkinson’s Foundation — from becoming a research advocate to joining a research study.

La enfermedad de Parkinson (EP) afecta a las personas de diferentes maneras, lo que representa un desafío para el desarrollo de nuevos tratamientos y terapias. PD GENEration: trazando el futuro de la enfermedad de Parkinson (PD GENEration: Mapping the Future of Parkinson’s Disease), el estudio global de la Parkinson's Foundation que ofrece pruebas y consejería genética sin costo para las personas diagnosticadas con la EP, está ayudando a los investigadores a superar este reto mediante la creación de una amplia base de datos genéticos para su análisis.

La diversidad de datos —es decir, tener información genética acerca de la EP de personas de todo el mundo— crea una base sólida para impulsar los avances en la investigación. Sin embargo, los miembros hispanos y latinos de la comunidad de la EP a menudo enfrentan barreras significativas tanto para vivir bien con la enfermedad de Parkinson como para participar en la investigación. Con esto en mente, la Parkinson’s Foundation se ha asociado con el Consorcio Latinoamericano de Investigación sobre la Genética de la Enfermedad de Parkinson (LARGE-PD, por sus siglas en inglés) para llevar el estudio PD GENEration a nuevos países.

Esta expansión no sólo fortalece la base de datos genéticos de la EP para uso de los investigadores, sino que también fomenta el objetivo del estudio de proporcionar pruebas y consejería genética a todas las personas diagnosticadas con la EP, sin importar en qué parte del mundo se encuentren.

Preparar una expansión exitosa

Expandir un estudio a nuevos países requiere tiempo, esfuerzo y planificación para que todo salga bien. Para ayudar a dicha expansión, PD GENEration colabora estrechamente con LARGE-PD, un estudio genético de la EP que se desarrolla en Latinoamérica desde 2006.

"Realizamos encuestas para entender el modelo de los sistemas de salud, que varían según el país y la institución, y la mejor manera de integrar los dos estudios para obtener los datos de mayor impacto", dijo Rebeca De León, directora de investigación clínica de la Parkinson's Foundation.

En 2024, se eligieron cinco centros LARGE-PD para comenzar a ofrecer pruebas y consejería genética de PD GENEration en Colombia, Chile, México, Perú y El Salvador. En colaboración con Indiana University School of Medicine, se diseñaron e implementaron programas de formación especializada en estos centros para garantizar que los resultados genéticos se devolvieran a los participantes. En tan sólo unos meses, estos centros inscribieron a 1,015 nuevos participantes y certificaron a 26 médicos para que devolvieran los resultados de las pruebas genéticas.

"El acceso a las pruebas y la consejería genética ha sido una laguna importante en LATAM", dijo el Dr. Ignacio Mata, coordinador de LARGE-PD y profesor de la Cleveland Clinic. "PD GENEration es un gran paso hacia la medicina de precisión, ya que proporciona a médicos y pacientes la información genética necesaria para ofrecer el mejor tratamiento posible a cada individuo".

Mantener el impulso

La Parkinson's Foundation está entusiasmada por continuar esta exitosa colaboración en América Latina, trabajando para proporcionar pruebas genéticas y asesoramiento a más personas con la enfermedad de Parkinson. Próximamente, PD GENEration incorporará nuevos centros en Argentina, Brasil, Honduras y Uruguay, ampliando así el acceso al estudio a un número aún mayor de países.

"Hemos establecido una sólida red de colaboración con centros de investigación y especialistas locales, facilitando enormemente la integración del estudio en cada país", dijo Anny Coral-Zambrano, gerente senior de Investigación Clínica de la Parkinson's Foundation. "Hoy, el proceso funciona sin problemas gracias a las soluciones innovadoras que hemos implementado".

Las campañas de divulgación en los alrededores de los sitios existentes también están ayudando a informar del estudio a las comunidades locales de la EP. "Para apoyar el reclutamiento, hemos estado llevando a cabo eventos educativos acerca de la investigación en los que ofrecemos el estudio", dijo Rebeca. "Algunos centros  incluso se desplazan a zonas remotas para prestar servicios médicos y ofrecer el estudio a quienes no pueden llegar a los centros".

El primer evento de PD GENEration en la Ciudad de México atrajo a más de 200 asistentes, de los cuales 82 se inscribieron al estudio en el evento. El evento contó con paneles acerca del Parkinson, la cognición, el ejercicio y la investigación y con la participación de más de 20 médicos. Un evento inaugural similar en Cali (Colombia) contó con 215 asistentes y ofreció una clase de zumba, actividades de estimulación cognitiva y un panel de expertos en genética.

El futuro de PD GENEration en América Latina

Con PD GENEration ahora activo en varios países de América Latina y llegando a más comunidades tradicionalmente desatendidas por la investigación de la EP, más personas que viven con esta enfermedad pueden obtener información valiosa acerca de su enfermedad a través de las pruebas y consejería genética. A medida que  aumente la diversidad de la información genética en la base de datos de PD GENEration, también lo hará la comprensión de la enfermedad por parte del campo de investigación de la EP, lo que permitirá impulsar avances significativos en su tratamiento.

En el proceso de expansión, los líderes de PD GENEration en la región han adquirido aprendizajes clave sobre cómo interactuar con poblaciones diversas, lecciones que fortalecerán las estrategias de divulgación e impacto del estudio en el futuro.

Las colaboraciones con consorcios como LARGE-PD permiten que la comunidad avance unida hacia un futuro en el que las personas con EP puedan vivir mejor gracias a mejoras continuas en la atención médica y en la investigación científica.

Aprenda más acerca de PD GENEration e inscríbase hoy mismo.

Many people with Parkinson’s disease (PD) use Levodopa, a dopamine-replacement medication, that helps improve quality of life. However, continuous use of levodopa often leads to new movement symptoms called levodopa-induced dyskinesia (LID).

Dyskinesias in Parkinson’s disease are involuntary, erratic movements that can affect different parts of the body. It is estimated that more than 50% of people who take levodopa for PD symptoms develop LID, but the neurological reasons behind this phenomenon are still not well understood.

Jeroen Habets, MD, PhD, a recipient of a Parkinson’s Foundation Postdoctoral Fellowship, seeks to identify brain wave “biomarkers” of LID, highlighting regions of the brain that go awry during LID. Then, his study will use magnetic stimulation therapy to reduce or eliminate LID completely. 

“We are using a noninvasive recording technique to try and understand what happens at the surface of the brain during these periods where patients have dyskinesia,” said Dr. Habets. “We want to better understand what happens when they move involuntarily. We hope to understand better how the whole movement network functions in Parkinson’s disease and specifically this symptom.”

The patterns of neuron activation in the brain used to achieve tasks like movement, memory recall and much more can be observed and measured as brain waves. Different frequencies — the speed and intensity of the patterns — of brain waves are associated with different mental states and activities, such as the slow, calm delta waves of deep sleep or rapid, intense gamma waves of alertness and agitation.

From the lab of Andrea Kühn, MD, at the Charité University Hospital in Berlin, Germany, Dr. Habets uses a machine called a magneto-encephalograph to study participants with PD and visualize the brain wave activity that occurs during bouts of LID. 

By measuring each participant’s brain waves patterns and how they change during LID, Dr. Habets hopes to find regions in the brain that could be a target for treatment. His study will use non-invasive transcranial magnetic stimulation (TMS), which involves using guided magnetic waves to affect brain wave activity. 

Knowing what regions of the brain and which frequencies of brain waves are involved with LID could lead to personalized TMS treatments that alleviate debilitating levodopa side effects.

“During dyskinesia, some processes at the surface of the brain are more active than they should be or than they normally are,” said Dr. Habets. “Previous research showed that if you use magnetic stimulation, which is noninvasive and transmitted through a coil held over the head, you can give magnetic pulses to decrease activity at the surface of the brain and that patients over the hours afterwards developed less dyskinesia.”

Dr. Habets said finding a way to implement this treatment into patients’ daily lives is still a challenge, but researchers need to better understand dyskinesia to solve that problem.

He is hopeful about the potential of this research and grateful for the donors who make research grants like the one he received from the Parkinson’s Foundation possible.

“These donors are giving us time, giving us the opportunity to learn and to develop ourselves,” said Dr. Habets. “I think it has two big effects. There is a direct effect in the science that we do, but it is also growing careers. These funds, especially for young researchers, are very motivating grants to get and inspire us to move forward in our careers.”

 Meet more Parkinson’s researchers! Explore our My PD Stories featuring PD researchers.

El bioquímico Kevin McFarthing recuerda todo acerca de su diagnóstico de la enfermedad de Parkinson (EP). "Me lo diagnosticaron a las 4 p.m. del 10 de diciembre de 2012", dijo. Desde entonces, ha estado tras la pista de una cura, catalogando potenciales terapias contra el Parkinson como coeditor de Clinical Trial Highlights, Journal of Parkinson's y organizando a lista Parkinson's Hope List, una base de datos de más de 350 estudios en curso.

En Expert Briefings-Charlas con expertos: Los últimos avances en la investigación y el tratamiento del Parkinson, el Dr. McFarthing comparte los últimos avances en la investigación y de qué manera el participar en estudios clínicos nos acerca a una cura.

La urgencia por avanzar

El Parkinson va en aumento. Un estudio apoyado por la Parkinson's Foundation reveló que 90,000 personas en los EE.UU. son diagnosticadas con la enfermedad cada año. Para 2040, más de 12 millones de personas en todo el mundo vivirán con la EP. Las compañías farmacéuticas están interesadas en acelerar una cura. La identificación de nuevas terapias contra el Parkinson es una de las principales prioridades de la investigación y el desarrollo farmacéuticos.

"Todos tenemos nuestra propia visión de lo que podría significar la cura", dijo el Dr. McFarthing. Para algunos, podría ser "una solución mágica para resolver los síntomas y devolver nuestras capacidades a como éramos antes". Otros podrían esperar "un fármaco que brinde otros 10 años de vida sin síntomas".

Los desafíos

Aunque las compañías farmacéuticas están buscando terapias avanzadas para el Parkinson, los costos son elevados y la competencia por la financiación es fuerte. Innumerables medicamentos de prueba fracasan a menudo en el camino hacia un fármaco de éxito para el sistema nervioso central, como la levodopa (la actual terapia de primera línea contra el Parkinson, descubierta hace más de 50 años).

Según el Centro Tufts para el Estudio del Desarrollo de Medicamentos, una terapia para el sistema nervioso central puede costar más de $2 mil millones en investigación y tardar casi un 20% más que otros fármacos en desarrollarse.

El Parkinson es complejo. Los síntomas se manifiestan de forma diferente en cada persona, lo que dificulta un enfoque único para el tratamiento farmacológico. La participación en la investigación es esencial para descubrir las causas de la enfermedad y encontrar nuevos tratamientos para los síntomas que la gente ve —incluyendo el temblor, la rigidez y la lentitud de movimientos— y los diversos no motores que acompañan a la EP.

Investigaciones diversas y la inversión continua también son esenciales. Por suerte, como señala el Dr. McFarthing, "se está realizando mucho trabajo".

En todo el mundo hay más de 100 estudios que exploran formas de mejorar diversos síntomas de la EP. Más de 250 estudios están investigando posibles terapias modificadoras de la enfermedad, tratamientos que podrían ralentizar, detener o invertir el avance de la enfermedad.

Sacando nuevos tratamientos a la luz

Tras identificar un nuevo tratamiento prometedor para una enfermedad mediante estudios observacionales, animales o celulares, los investigadores buscan financiación y participantes para ensayos clínicos. Estos ensayos, cuidadosamente supervisados, se realizan por fases, —normalmente probando un agente activo frente a un placebo—, para determinar su seguridad y eficacia. Por lo general, una terapia prospectiva debe superar con éxito las fases 1, 2 y 3 antes de que la Administración de Alimentos y Medicamentos de los EE.UU. (Food and Drug Administration o FDA, por sus siglas en inglés) decida si una empresa puede presentar una solicitud de nuevo fármaco.

Algunos de los estudios de tratamiento a tener en cuenta son:

Terapias para la discinesia (movimientos involuntarios, erráticos y retorcidos), dirigidas a los efectos secundarios asociados al uso prolongado de la levodopa:

• Celon Pharma S.A. obtuvo resultados positivos de fase 2 con su CPL'36 oral, de una sola toma al día. El fármaco dificulta la actividad de la enzima fosfodiesterasa 10a, aumentando los niveles cerebrales de ciertos mensajeros químicos para mejorar el control motor. 

• Tras finalizar los ensayos de fase 2B, el mesdopetam (IRL790) de IRLAB no alcanzó los criterios de valoración primarios. Los investigadores siguen evaluando su potencial terapéutico. El fármaco bloquea la actividad del receptor D3 de la dopamina, que puede estar relacionado con la discinesia inducida por la levodopa.

• La fase 1 de investigación del AV-101 de Vistagen está en curso. El fármaco actúa sobre los receptores de N-metil-D-aspartato (NMDA) que tienen fallas. Unos receptores sanos son fundamentales para la comunicación entre las células nerviosas del cerebro.

• Se espera que Sinopia Biosciences inicie los ensayos clínicos de un candidato preclínico a fármaco contra la discinesia: el SB-0110.

Este fármaco maximiza el tiempo en “on”, el periodo en que la levodopa proporciona el máximo control de los síntomas. A medida que progresa el Parkinson, la persona puede experimentar más tiempos en “off". Las terapias destinadas a prolongar el tiempo en "on" incluyen:

• Vyalev (Produodopa en Europa), disponible en los EE.UU. desde 2024. Esta nueva formulación de levodopa está dirigida al Parkinson avanzado. Una bomba portátil administra una infusión constante de medicamento bajo la piel, proporcionando un control más constante de los síntomas. Vyalev también puede mejorar la calidad del sueño, los tiempos en "off" a primera hora de la mañana y otros síntomas.

• Tavapadon estimula determinados receptores de dopamina para mejorar la función motora y reducir los efectos secundarios. Los agonistas dopaminérgicos actuales no son selectivos y los efectos secundarios pueden incluir comportamientos compulsivos y alucinaciones visuales. Tavapadon proporcionó un buen control de los síntomas en los ensayos de fase 3 como medicación independiente y cuando se utilizó junto con la levodopa. El fabricante, AbbVie, tiene previsto presentar este año una solicitud de nuevo fármaco a la FDA.

La investigación con células madre es un desafío. Implica cirugía cerebral y, tras la implantación de células, se necesita tiempo para ver si los síntomas mejoran. A pesar de los numerosos estudios con células madre para el Parkinson, los investigadores no habían pasado de la fase 2 hasta hace poco:

• BlueRock Therapeutics, una división de Bayer, presentó datos positivos de fase 1 sobre bemdaneprocel, una terapia celular que busca sustituir las neuronas productoras de dopamina que se pierden a causa del Parkinson. Con base en estos datos, la FDA concedió al fármaco la designación de terapia avanzada de medicina regenerativa, permitiéndole pasar a los ensayos de fase 3 a principios de 2025.

Algunas de las terapias en investigación prometedoras para detener o frenar la progresión de la EP son:

• Factores de crecimiento neurotróficos, moléculas que estimulan el crecimiento de los nervios. Estos podrían beneficiar a las personas con Parkinson. El AB-1005 de AskBio, un factor neurotrófico derivado de una línea celular glial (GDNF, por sus siglas en inglés) administrado directamente al cerebro, puede minimizar la pérdida de dopamina asociada al Parkinson.

• Beneficios neuroprotectores potenciales del factor neurotrófico derivado del cerebro y del factor neurotrófico dopaminérgico cerebral.

• Los inhibidores de la proteína inflamasona NLRP3 pretenden bloquear la activación de moléculas inflamatorias relacionadas con la pérdida de dopamina en el Parkinson.

• Posibles beneficios neuroprotectores de la nicotinamida ribósida, una forma de la vitamina B3.

Los investigadores también están explorando formas de prevenir la acumulación de la proteína alfa-sinucleína, la proteína que forma cúmulos tóxicos, llamados cuerpos de Lewy, en el cerebro de las personas con la EP:

• Los estudiso de fase 2 de prasinezumab de Roche, dirigidos a la acumulación y propagación de la alfa-sinucleína. El estudio no alcanzó su objetivo, pero la compañía planea buscar datos que potencialmente muestren beneficios del prasinezumab en el Parkinson inicial.

• Annovis Bio Fase 3 concluyó recientemente los estudios sobre buntanetap, un fármaco que reduce la producción de alfa-sinucleína. Buntanetap no alcanzó los objetivos del estudio. No obstante, la empresa tiene previsto seguir investigando el fármaco.

• Las mutaciones en el gen GBA  (que produce la enzima glucocerebrosidasa, o Gcase) son uno de los más frecuentes factores genética de riesgo de la EP. Varias empresas están investigando si los compuestos que estimulan la actividad Gcase pueden mejorar la función motora u ofrecer neuroprotección. 

  • Se ha demostrado que el Ambroxyl, un medicamento para la tos utilizado para reducir la flema, aumenta la actividad de la Gcase en personas con Parkinson. Puede eliminar los cúmulos tóxicos de alfa-sinucleína. Está en marcha un ensayo de fase 3.

• Las mutaciones del gen LRRK2 son la causa más frecuente de la EP genética. Estudios de investigación en cuatro empresas están explorando cómo los inhibidores de la LRRK2 podrían aportar beneficios neuroprotectores. Otras cinco empresas están en fase de ensayos clínicos.

Otras posibles terapias modificadoras de la enfermedad son los agonistas del GLP-1. Principalmente desarrollados para controlar la diabetes, los agonistas del GLP-1 imitan la hormona humana péptido-1, similar al glucagón (GLP-1), que controla el azúcar en sangre y el apetito.  Algunos delos estudios recientes sobre agonistas del GLP-1 son:

• Terapia con lixisenatida. Los participantes con la EP inicial en el ensayo de fase 2 experimentaron una menor progresión de la discapacidad motora que el placebo a los 12 meses. Sin embargo, muchos participantes experimentaron efectos secundarios gastrointestinales.

• La liraglutida mostró una mejoría significativa en algunos síntomas no motores, pero ninguna diferencia en los síntomas motores durante el estudio de fase 2.

• La investigación de fase 3 sobre la exenatida demostró que el fármaco era seguro y bien tolerado, pero no mostró ninguna ventaja sobre el placebo en el Parkinson.

• Las investigaciones de fase 2 de NLY01, exenatida modificada, no mostraron mejorías en los síntomas del Parkinson.

• Los investigadores están a la espera de los resultados de un estudio clínico de fase 2 del Hospital Universitario de Oslo que explora el valor potencial de la semaglutida en el Parkinson.

Construir sobre la esperanza

La única manera de acelerar el desarrollo de tratamientos que puedan ralentizar o detener el Parkinson es a través de una financiación amplificada y continua. El Fondo de Biotecnología Virtual para el Parkinson (Parkinson's Virtual Biotech) , una asociación entre la Parkinson's Foundation y Parkinson's UK, financia 11 nuevos medicamentos y terapias bajo investigación y desarrollo.

La iniciativa Edmond J. Safra Accelerating Clinical Treatments for Parkinson's Disease (EJS-ACT PD, por sus siglas en inglés) tiene como objetivo acelerar las terapias de prueba de fármacos seguros utilizando diseños de ensayos multibrazo y multietapa (MAMS, por sus siglas en inglés), un enfoque más novedoso y rentable.

Los ensayos MAMS permiten a los investigadores evaluar varios tratamientos a la vez contra un placebo. Los investigadores pueden descubrir lo que funciona y descartar lo que no, sin tener que desmontar un ensayo y empezar de nuevo. El objetivo es facilitar una transición fluida y rentable a la siguiente fase de los ensayos y comercializar más rápidamente nuevas terapias eficaces. Hay otros ensayos MAMS para Parkinson en marcha en todo el mundo.

"Esperamos tener más fracasos que éxitos debido a la naturaleza de lo que intentamos hacer", dijo McFarthing. "Pero creemos que algo resultará de esto".

Cómo participar en la investigación sobre el Parkinson:

1. Participar en PD GENEration.

2. Únase a un ensayo o estudio sobre el Parkinson.

3. Conviértase en defensor de la investigación.

Inflammatory bowel disease (IBD) — conditions like Crohn's disease and ulcerative colitis — are linked to an increased risk of developing Parkinson's disease (PD), a neurodegenerative disorder affecting movement. Scientists are working to figure out why the diseases are linked, and a key player may be the community of microbes living in our gut, often referred to as the gut microbiome.

The gut microbiome is a complex ecosystem of trillions of bacteria, fungi, viruses and other microorganisms that live in our digestive system. It plays a crucial role in digestion, immunity and brain health. An imbalance in this gut microbial community, known as gut dysbiosis, can contribute to various health issues.

A recent study compared the gut microbiomes of people with Parkinson’s disease, IBD and healthy individuals. It also examined larger, publicly available microbiome data from people with Parkinson’s or IBD. This research is the first to directly compare gut microbiomes across these three groups.

Parkinson’s Foundation Scientific Advisory Board member Malú Gámez Tansey, PhD, led the study, which was published in npj Parkinson's Disease; Michael S. Okun, MD, Parkinson's Foundation National Medical Advisor, was also a study contributor. The results revealed previously unknown similarities between the gut microbiomes of people with Parkinson’s and those with IBD. 

The study found a reduced number of a certain type of microbe in both people with inflammatory bowel disease and Parkinson’s, suggesting that these specific microbes may influence the risk of Parkinson’s.

Study Results

The study recruited 54 people with Parkinson’s, 24 people with IBD and 16 people without these diseases. The researchers used fecal samples and special techniques to identify the microbes that make up each participant’s microbiome. When they compared the microbes, they observed clear differences as well as certain overlaps in the species of bacteria in the guts of people with IBD and Parkinson’s compared to healthy individuals. 

Additionally, in large sets of data from past studies of people with IBD or Parkinson’s, they found that even though there are unique changes in each condition, there are also specific bacteria and metabolic processes that are either more or less common in both IBD and Parkinson’s.

In people with Parkinson’s or IBD, the study found that there tended to be a decrease in the levels of certain types of bacteria known for producing short-chain fatty acids (SCFAs), which are important fuel and signaling molecules for our gut and brain. The study highlighted a few specific SCFA-producing bacteria that were lower in both the Parkinson’s and IBD groups. 

Furthermore, researchers also found a reduction in the biological machinery responsible for producing the bacteria in both conditions. As SCFAs play a role in maintaining gut health and may have neuroprotective effects, these findings suggest that the depletion of SCFA-producing bacteria in people with IBD might increase their susceptibility to developing Parkinson's disease. A lack of these beneficial compounds could potentially impact brain health over time. 

This research underscores the connection between our gut and our brain — often referred to as the gut-brain axis. It suggests that a healthy and diverse gut microbiome may be important for brain and gut health, and a lack of these beneficial bacteria could potentially impact brain health over time. However, more studies are needed to show whether interventions to change diet or microbiome could help with IBD or Parkinson’s.

Highlights

• The study recruited 54 people with Parkinson’s, 24 people with IBD and 16 people without these diseases. The researchers used special techniques to identify the microbes that make up each participant’s microbiome. They also analyzed publicly available data from past studies of people with IBD or Parkinson’s.

• They found previously unknown overlap between the gut microbiomes of people with Parkinson’s and people with IBD.

• They found a decrease in the amount of certain types of bacteria known for producing short-chain fatty acids (SCFAs), which are important fuel and signaling molecules for our gut and brain, in both people with Parkinson’s and IBD.

• Their findings suggest that the depletion of these important bacteria in individuals with IBD might contribute to an environment that increases their susceptibility to developing Parkinson's disease.

What does this mean?

This study has identified new shared features between the microbiomes of people with PD and IBD. Because there is a link between these two conditions, improving our understanding of the specific microbes involved in both diseases may potentially lead to new therapies. 

While this research provides insights into the potential link between gut dysbiosis, IBD, and Parkinson's disease, more studies with larger sample sizes are needed to fully understand the complex mechanisms at play and whether any interventions could help.

What do these findings mean to the people with PD right now?

About 80% of people with Parkinson's experience gastrointestinal (GI) issues. These issues can develop up to 10-20 years before a PD diagnosis. Therefore, the gut microbiome is a ripe target for future treatments that could potentially stop or slow PD progression at an early stage. 

However, the gut microbiome is very complex and unique to each person. If you are suffering from gastrointestinal issues, try eating more fiber-rich foods and less starchy ones, drinking more fluids and increasing exercise. Speak to your doctor before trying pro- or pre-biotic supplements that alter your gut microbiome, since they may affect people differently. 

PD-related gastroparesis (the impaired ability to empty the contents of the stomach) and other GI issues can impact how medications are absorbed. People with gut issues may find PD medications such as carbidopa/levodopa take longer to take effect or seem less effective. Additionally, the medications themselves can alter the structure of your gut microbiome. Bring up any GI issues to your PD doctor who might refer you to a gastroenterologist, a doctor specializing in GI issues. 

Learn More

The Parkinson’s Foundation believes in empowering the Parkinson’s community through education. Learn more about PD and the topics in this article through our below resources, or by calling our free Helpline at 1-800-4PD-INFO (1-800-473-4636) for answers to your Parkinson’s questions.

• Tackling Neuropathy, Fatigue and GI Issues in PD

• How an Innovative Research Center Studies the Gut–Brain Connection

• Podcast: The Role of the Microbiome in PD: Part One and Part Two

• The PD Gut-Brain Connection

The Parkinson’s Foundation study PD GENEration: Mapping the Future of Parkinson’s Disease provides genetic testing and counseling that empowers people with Parkinson’s disease (PD) to discover new insights about their genetic makeup and their family’s risks. Its valuable data also connects people to research. But what many may not realize is that PD GENEration is also here to drive research towards a cure.

Next-generation clinical trials for Parkinson’s disease are targeting the genetics underlying the disease. These trials require participants to carry known genetic mutations to test the safety and effectiveness of these new therapies or drugs.  Equipped with knowledge of their mutations, participants in PD GENEration can move science — and potentially a cure — forward by participating in trials that rely upon their unique genetic backgrounds.

How PD GENEration Helped Activate the ACTIVATE Trial

In 2023, the biopharmaceutical company BIAL began a clinical study, nicknamed “ACTIVATE,” of its promising new PD drug called BIA 28-6156. This drug was designed to restore the activity and function of a protein called GCase, which is impaired in people with Parkinson’s who have a mutation in the GBA1 gene. For that reason, the ACTIVATE study needed participants with PD and a confirmed GBA1 mutation.

“Finding enough patients with this mutation is a major challenge,” said Kathleen McKee, MD, MPH, Director of Movement Disorders at Intermountain Medical Center in Salt Lake City, UT. “If patients are not already identified through prior genetic testing, then you are looking at six months to a year to get all your patients through and test them, which is too slow for enrollment.”

Intermountain Medical Center was one of the healthcare sites that BIAL reached out to when it first began recruiting ACTIVATE study participants. Dr. McKee was tasked with finding which people with PD at their medical center had a GBA1 mutation and could be eligible for the study. 

This task was made much simpler as many members of the center’s PD community had already received genetic testing and counseling through PD GENEration. “We were able to look at a spreadsheet and instantly identify all our PD patients who had identified their GBA1 mutation through PD GENEration,” said Dr. McKee. 

With more than 24,000 people globally enrolled in PD GENEration and growing every month, this ease of finding eligible ACTIVATE study participants was likely accelerated for many other collaborating healthcare sites as well. 

In just under a year, the BIAL study met its recruitment goal of more than 230 people with PD and a GBA1 mutation, an impressive feat in no small part due to PD GENEration. With the study designed to monitor BIA 28-6156's effects over a year and a half for each participant, initial results from this study are expected to be released in mid-2026.

Beginning the Path to a Cure

PD affects people in different ways, largely because of the wide range of genetic mutations associated with disease. Through PD GENEration, people with PD can not only better understand their personal diagnoses but also use that knowledge to help support studies investigating treatments designed for their specific PD mutations.

“I’m excited for PD patients to participate in trials unique to their mutation. I think this is how we will start to discover the cure for PD,. We will discover the cure for one genetic mutation, it will help us learn more about the disease overall, and for patients with that mutation it will be life changing,” said Dr. McKee.

Learn More 

The Parkinson’s Foundation works to improve care for people with PD and advance research toward a cure. Learn more with these resources: 

• Discover how we are working to close gaps in knowledge about PD: Advancing Research

• Learn about and enroll in PD GENEration — a global genetics study that provides genetic testing and counseling at no cost for people with Parkinson’s.

• Explore ways to get involved in the Parkinson’s Foundation — from becoming a research advocate to joining a research study.

Biochemist Kevin McFarthing, PhD, remembers everything about his Parkinson’s disease (PD) diagnosis. “I was diagnosed at 4 p.m. on the 10th of December in 2012,” he said. Ever since, he’s been on the trail of a cure, cataloguing potential Parkinson’s therapies as a joint editor of Clinical Trial Highlights, Journal of Parkinson’s and curating the Parkinson’s Hope List, a database of more than 350 ongoing studies.

In the Parkinson’s Foundation Expert Briefing: The Latest Advances in Parkinson’s Research and Treatment, Dr. McFarthing shares the latest advances in research and how participating in clinical studies brings us closer to a cure.

An Urgency for Progress

Parkinson’s is on the rise. A Parkinson’s Foundation-supported study revealed that 90,000 people in the U.S. are diagnosed with the disease every year. By 2040, more than 12 million people worldwide will live with PD. Pharmaceutical companies are invested in speeding a cure. Identifying new Parkinson’s therapies is among top pharmaceutical research and development priorities.

“We all have our own views of what the cure might mean,” Dr. McFarthing said. For some, it might be “a magic bullet to resolve symptoms and restore our abilities back to where we were before.” While others might hope for “a drug that gives another 10 years of symptom-free life.”

The Challenges

Though drug companies are pursuing advanced therapies for Parkinson’s, costs are high and competition for funding is steep. Countless trial medications often fail in the lead-up to a successful central nervous system drug, such as levodopa (the current first-line Parkinson’s therapy, discovered more than 50 years ago).

According to the Tufts Center for the Study of Drug Development, a central nervous system therapy can cost more than $2 billion in research and take nearly 20% longer than other drugs to develop.

Parkinson’s is complex. Symptoms manifest differently in each person, making a one-size-fits-all approach to drug therapy tricky. Research participation is essential to uncover the causes behind the disease and to find new treatments for the symptoms people see — including tremor, rigidity and slowed movements — and the many non-movement symptoms that accompany PD.

Diverse research and continued investment are also essential. Luckily, as Dr. McFarthing points out, “There is a massive amount of work going on.”

Globally, there are more than 100 studies exploring ways to improve various PD symptoms. More than 250 are investigating potential disease-modifying therapies, treatments that could potentially slow, stop or reverse disease progress.

Bringing New Treatments to Light

After identifying a promising new disease treatment through observational, animal or cell studies, researchers seek clinical trial funding and participants. These carefully monitored trials are done in phases — usually testing one active agent against a placebo — to determine safety and effectiveness. Typically, a prospective therapy must successfully pass Phases 1, 2 and 3 before the Food and Drug Administration (FDA) decides whether a company can submit a new drug application.

Treatment studies to watch include:

Dyskinesia (involuntary, erratic, writhing movements) therapies targeting side effects associated with long-term levodopa use:

• Celon Pharma S.A.’s oral, once-daily CPL'36 demonstrated positive Phase 2 results. The drug hinders activity phosphodiesterase 10a enzyme activity, increasing brain levels of certain chemical messengers to improve motor control.  

• After finishing Phase 2B trials IRLAB’s mesdopetam (IRL790) failed to meet primary endpoints. Researchers are continuing to evaluate its treatment potential. The drug blocks dopamine D3 receptor activity, which may be linked to levodopa-induced dyskinesia.

• Phase 1 investigation of Vistagen’s AV-101 is underway. The drug targets malfunctioning N-methyl-D-aspartate (NMDA) receptors. Healthy receptors are key to nerve cell communication in the brain.

• Sinopia Biosciences is expected to begin clinical trials for a preclinical dyskinesia drug candidate SB-0110.

Drugs that maximize “on” time — the period levodopa provides peak symptom control. As Parkinson’s progresses, a person can experience more “off” times. Therapies intended to extend “on” time include:

• Vyalev (Produodopa in Europe), available in the U.S. as of 2024. This new levodopa formulation targets advanced Parkinson’s. A portable pump delivers a steady infusion of medicine under the skin, providing more consistent symptom control. Vyalev may also improve sleep quality, early morning “off” times and other symptoms.

• Tavapadon stimulates select dopamine receptors to improve movement function and reduce side effects. Current dopamine agonists are nonselective and side effects can include compulsive behaviors and visual hallucinations. Tavapadon delivered good symptom control in Phase 3 trials as a standalone medication and when used in addition to levodopa. The manufacturer, AbbVie, plans to submit a new drug application to the FDA this year.

Stem cell research is challenging. It involves brain surgery and, following the implantation of cells, it takes time to see whether symptoms improve. Despite many stem cell studies for Parkinson’s, researchers had not moved beyond Phase 2 until recently:

• BlueRock Therapeutics, a division of Bayer, submitted positive Phase 1 data on bemdaneprocel – cell therapy that aims to replace dopamine-producing neurons lost in Parkinson’s. Based on the data, the FDA granted the drug a regenerative medicine advanced therapy designation, allowing it to move into Phase 3 trials in early 2025.

 Investigational therapies holding promise to stop or slow PD progression include:

• Neurotrophic growth factors, molecules that stimulate nerves to grow. These may benefit people with Parkinson’s. AskBio’s AB-1005, a glial cell line-derived neurotrophic factor (GDNF) delivered directly to the brain, may minimize dopamine loss associated with Parkinson’s.

• Potential neuroprotective benefits of brain-derived neurotrophic factor and cerebral dopamine neurotrophic factor.

• NLRP3 Inflammasone protein inhibitors aim to block activation of inflammatory molecules linked to loss of dopamine in Parkinson’s.

• Potential neuroprotective benefits of nicotinamide riboside, a form of vitamin B3.

Researchers are also exploring ways to prevent buildup of alpha-synuclein protein, the protein that forms toxic clumps, called Lewy bodies, in the brain of people with PD:

• Roche’s Phase 2 studies of prasinezumab, targeted accumulation and spread of alpha-synuclein. The study did not meet its goal, but the company plans to pursue data that potentially shows benefits of prasinezumab in early Parkinson’s.

• Annovis Bio Phase 3 recently concluded studies of buntanetap, a drug that reduces alpha-synuclein production. Buntanetap did not meet the study’s goals. However, the company plans to continue investigating the drug.

• Mutations in the GBA gene (which makes the enzyme glucocerebrosidase, or Gcase) are one of the most common genetic risk factors for PD. Several companies are researching whether compounds that stimulate Gcase activity can improve motor function or offer neuroprotection. 

  • Ambroxyl, a cough medicine used to decrease phlegm, has been shown to increase Gcase activity in people with Parkinson’s. It may clear away toxic alpha-synuclein clumps. A Phase 3 trial is underway.

  • LRRK2 gene mutations are the most common cause of genetic PD. Investigational studies at four companies are exploring how LRRK2 inhibitors might provide neuroprotective benefits. Another five companies are in clinical trials.

Other potential disease-modifying therapies include GLP-1 agonists. Primarily developed to control diabetes, GLP-1 agonists mimic the human glucagon-like peptide-1 (GLP-1) hormone, which controls blood sugar and appetite. Recent GLP-1 agonist studies include:

• Lixisenatide therapy. Phase 2 trial participants with early PD experienced less motor disability progression than placebo at 12 months. However, many participants experienced gastrointestinal side effects.

• Liraglutide showed significant improvement in some non-motor symptoms, but no difference in motor symptoms during Phase 2 study.

• Phase 3 investigation of exenatide showed the drug was safe and well-tolerated but showed no advantage over placebo in Parkinson’s.

• Phase 2 investigations of NLY01, modified exenatide, did not show improvement in Parkinson’s symptoms.

• Researchers are awaiting results of a Phase 2 Oslo University Hospital clinical study exploring the potential value of semaglutide in Parkinson’s.

Building on Hope

The only way to speed the development of treatments that can slow or stop Parkinson’s is through amplified, ongoing funding. The Parkinson’s Virtual Biotech, a partnership between the Parkinson’s Foundation and Parkinson’s UK, is funding 11 new medications and therapies in research and development.

The Edmond J. Safra Accelerating Clinical Treatments for Parkinson's Disease (EJS-ACT PD) Initiative aims to fast-track safe drug testing therapies using multi-arm multi-stage (MAMS) trial designs — a newer, more cost-effective approach.

MAMS trials allow researchers to assess multiple treatments at once against a placebo. Researchers can discover what is working and discard what is not, without dismantling a trial and starting again. The goal is to facilitate a seamless, cost-effective transition to the next phase of trials and bring effective new therapies to market faster. Other Parkinson’s MAMS trials are underway around the world.

“We expect to get more failures than successes because of the nature of what we’re trying to do,” McFarthing said. “But we believe that something will come out of this.”

How to get involved in Parkinson’s research:

1.      Participate in PD GENEration.

2.      Join a Parkinson’s trial or study.

3.      Become a Research Advocate.

Parkinson’s disease (PD) affects people in different ways, which is a challenge when trying to develop new treatments and therapies. PD GENEration: Mapping the Future of Parkinson’s Disease, the global Parkinson’s Foundation study that provides genetic testing and counseling at no cost for people diagnosed with PD, is helping researchers overcome this challenge by developing a large PD genetic database for analysis. 

Diversity of data — having genetic information about PD from people across the world — creates a strong foundation to propel research breakthroughs. However, Hispanic and Latino members of the PD community often face distinct barriers to living well with Parkinson’s and contributing to PD research. With that in mind, the Parkinson’s Foundation partnered with the Latin American Research consortium on the Genetics of Parkinson’s Disease (LARGE-PD) to expand the PD GENEration study to new countries.  

This expansion not only strengthens the PD genetics database for researchers to utilize but also furthers the study’s goal of providing genetic counseling and testing to anyone with PD, anywhere in the world. 

Setting Up a Successful Expansion 

Expanding a study to new countries requires considerable time, effort and planning for everything to run smoothly. To assist with such expansion, PD GENEration works closely with LARGE-PD, a PD genetics study that has been underway in Latin America since 2006. 

“We conducted surveys to understand the health systems model, which vary by country and institution, and how best to integrate the two studies to get the most impactful data,” said Rebeca De León, Director of Clinical Research for the Parkinson’s Foundation. 

In 2024, five LARGE-PD sites were chosen to begin offering PD GENEration genetic testing and counseling in Colombia, Chile, Mexico, Peru and El Salvador. In collaboration with Indiana University School of Medicine, specialized training programs were designed and implemented at these sites to ensure that genetic results were returned to participants. In just a few months, these sites enrolled 446 new participants and certified 16 clinicians to return genetic testing results. 

 “Access to genetic testing and counseling has been a significant gap in LATAM,” said Ignacio Mata, PhD, LARGE-PD Coordinator and Professor at the Cleveland Clinic. “PD GENEration is a major step toward precision medicine, providing empowering genetic information to clinicians and patients that is needed to deliver the best possible treatment for each individual.” 

Maintaining Momentum 

The Parkinson’s Foundation is enthusiastic about continuing this successful collaboration in Latin America, working to provide genetic testing and counseling to more people with Parkinson’s disease. Soon, PD GENEration will on-board new sites in Argentina, Brazil, Honduras and Uruguay — expanding study access to even more countries. 

“We have established a strong network of collaboration with research centers and local specialists, greatly facilitating the integration of the study in each country,” said Anny Coral-Zambrano, Senior Manager of Clinical Research for the Parkinson’s Foundation. “Today, the process runs smoothly because of the innovative solutions we've implemented.” 

Outreach campaigns in areas around the existing sites are also helping inform local PD communities of the study. “To support recruitment, we have been holding research educational events where we offer the study,” said Rebeca. “Some testing sites even travel to remote areas to provide medical services and offer the study to those who can't get to the centers.” 

PD GENEration’s first-ever event in Mexico City drew 200 attendees, with 82 joining the study at the event. The event featured panels on Parkinson’s, cognition, exercise, and research — and attracted more than 20 doctors. A similar inaugural event in Cali, Colombia, welcomed 215 attendees, offering a Zumba class, cognition games and an expert-led panel on genetics. 

The Future of PD GENEration in Latin America 

With PD GENEration now available throughout Latin America and expanding to more underserved PD communities, more people living with PD can gain valuable insights into their disease  through genetic testing and counseling. As the diversity of genetic information in the PD GENEration database increases, so will the PD research field’s understanding of the disease and lead to impactful treatment breakthroughs. 

Along the way, leaders in PD GENEration’s expansion into Latin America have also learned valuable lessons about engaging with diverse PD populations that will guide effective and impactful outreach for the study in the future. Collaborations between PD GENEration and groups like LARGE-PD help the community move forward, together, toward a world where people with PD can live better through improved care and research. 

Learn more about PD GENEration and enroll today.