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.
Meet a Researcher Aiming to Treat Levodopa-induced Dyskinesia
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.”
Ganando terreno: La búsqueda por mejorar e introducir nuevos medicamentos contra el Parkinson
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.
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 losagonistas 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:
Study Finds Potential Link Between Parkinson's and Gut Health
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.
How PD GENEration Accelerates Clinical Trial Recruitment
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.
For a long time, I knew something was wrong. Deep down inside I knew. My handwriting was getting bad, I had a tremor in my hand, my arms no longer swung when I walked, and I had trouble standing and walking because of my balance. I didn’t want it to be true. I prayed that it was not.
The first 10 years of my marriage was spent helping my Dad. He had Parkinson’s disease (PD). I did all the normal things a son would do. I did yard work, took him for haircuts and ran errands. I helped when I could. I was raising a young family myself and only had so much time.
We talked about support groups and clinical trials. He was set in his ways, hard and not willing to give. He told me that for him, going to a support group was like looking into his future. He didn’t need it.
Suddenly, my wife’s mother was diagnosed with Parkinson’s. I saw all the early signs and steady decline. I witnessed firsthand the impact and demands of being a primary caregiver that were placed on my wife.
I finally got up the courage to stop ignoring my symptoms. I had had enough of lying to myself and hiding it from others. It was time to get this out in the open. I have Parkinson’s disease. There, I said it. As it turned out, it was not a surprise to those who know me best.
The diagnosis was devastating, expected, but none the less devastating. I accepted it, after all I had been preparing myself for some time. What I didn’t expect, was the guilt I felt for my wife. I didn’t care about myself, but rather why was this happening to her? She cared for me and our family as we helped my dad. She cared for her mother for all those years, and now she was literally going to be caring for me. The guilt was overwhelming!
I was surprised; the basic treatment of Parkinson’s had not changed much since my dad’s diagnosis in the late 1980’s. A lot is now known and there are many new treatments to eliminate or reduce the symptoms. But for all intense purposes, you treat the symptoms. Slowing or halting the progression of this disease is still in the future. Everyone I talked with said, the single most important finding was to keep moving. If anything seems to slow the progression, it’s exercise.
My father and my mother-in-law both laid down and accepted it. I was not going to go without a fight. I was going to make the best of this situation. I am a firm believer that each life event is preparation for something else that will happen in your future. I am young, and in relatively good health, no heart problems, no cancer, good vitals and active. Surely, I’ve been placed into this position for a purpose?
As is her passion, my wife (she’s a librarian) immediately jumped into research mode. We set out to find the right doctor for us, and she started exploring emerging treatments and therapies. That lead us to clinical trials.
I knew nothing about clinical trials. How to find one, what was involved, what was expected, how long they lasted, the screening process, the commitment, the potential risks, the potential benefits and least of all what it would mean for me.
There are many places to look for clinical trials:
Once we contacted Quest, there was a screening process and a series of questions asked over the phone to determine if you are a potential candidate for a trial.
If you meet the criteria, you are invited to continue the qualification process, and an office visit is scheduled. The initial visit is generally a review of the information provided during the screening call and a physical exam.
An Informed Consent document is provided, which provides a detailed description of the specific clinical study. This tells you exactly what to expect and what is expected of you.
Assuming the screening process goes well, and you sign the consent form, a schedule is developed to meet the trial’s protocol. This details what is being done and when it will be. Phone calls, office visits and procedures. This schedule is different for every trial and reflects the study’s requirements and goals.
My PD research experiences have always been positive, I have received:
Early access to the newest drugs and therapies.
Access to expert medical care by physicians who are focused on advancing the treatment of Parkinson’s and have your best interest in hand and understand the ups and downs of PD.
Met others Parkinson’s patients on a similar journey, compared notes, created new friendships, realize that I’m not alone.
I have seen others that are in subsequent phases of a drug trial. Knowing I helped move that drug along earlier in its approval cycle.
As a patient volunteer in several trials, I have participated in simple trials that required a single office visit, drug studies that lasted 1 to 3 months and required several overnight stays and even completed a trial that required a 30-day inpatient stay.
I’ve got to tell you, my own fears and anxieties about doctors and medical procedures cause me more stress than the actual examination and procedure. I have consented to having my vitals taken, EKG’s, blood draws, CAT scans, MRI’s, DAT Scans, IV infusions and Lumbar Punctures. Not to mention the psychological evaluations and cognitive testing, which are more unnerving for me than any medical procedure!
Did you know that one of the biggest reasons bringing a new drug to market takes so long is the lack of patient volunteers to participate in clinical trials?
"Next to marrying my wife and fathering my children, participating in clinical trials is the single most rewarding accomplishment in my life."
I never expected this. I don’t do this to be the recipient of the advancement, but so others won’t have to endure this journey. I don’t kid myself. My Parkinson’s is progressing, and the development and approval of new drugs is a time-consuming process. This is my purpose!
My participation in clinical trials, overcoming my fears and anxieties, contributing to the advancement of a cure and knowing that my contribution to the Parkinson’s community may someday prevent others from having to walk this same path is my single greatest moment.
My wife and I act as a mentor team (person with PD and caregiver) for the newly diagnosed. We participate in a mentorship program and regularly learn from and reference Parkinson.org in emails and as resources to our mentees.
So, I end this by asking you to please consider volunteering for a clinical trial. We are on the verge of a cure. We need those both with and without Parkinson’s. Without your support, progress toward our common goal, a cure, will be slow in coming.
I was diagnosed with Parkinson’s disease (PD) in a strange way. I was at a pain clinic getting a steroid shot in my back when it was suggested that I should see a neurosurgeon. I agreed, so an appointment was made. When I met him, he kept looking at my hand. After a few minutes he stopped talking and said he wanted me to see a neurologist for an EMG (a diagnostic test that measures muscle response). Not being sure what that was I said OK, and another appointment was made.
When the neurologist appointment came, I met her and before the EMG I was asked many questions and went through a series of tests. Not really knowing why, but knowing there must be a reason, I complied. Finally, I had the EMG, and then a cognitive test.
She took very detailed notes the whole time and excused herself for a few minutes. When she came back, she said we had several things to talk about and proceeded to tell me that I had Parkinson’s.
My reaction was what it might feel like if you were hit in the face with a football. I never saw it coming.
The neurologist was very kind and explained what led to the diagnosis. It turns out the neurosurgeon noticed my tremors and sent me to her thinking that she needed to look further. It took me two weeks to process this information.
I was in complete denial but after that, I was able to take a physical therapy (PT) class designed for Parkinson’s called BIG movement. It has changed my life. It has been the best thing I could have ever done.
My outlook is positive, I am boxing now, I walk confidently, my balance is better. I participated in my first research study, the Parkinson’s Foundation genetics study, PD GENEration, because this hits as close to home as you can get. I want to do whatever I can to help find a cure so that hopefully no one in my family or anyone else’s family ever has to go through this experience.
I wanted to participate in this study for a couple reasons. The first was for my family. I felt it was important to find out if I had a genetic link to PD they wanted to know about. Once I submitted my genetic sample, I asked each person in my family if they wanted the results and told them I would respect their answer with no judgement. The second reason was for myself because having Parkinson’s has opened my eyes to just how much I have never known or understood, and more information could only help me.
It felt great to participate in this study because I felt that I was being proactive. For me, anything that can help get answers is one step closer to hopefully finding a cure for this disease.
I will tell anyone who is newly diagnosed, don't feel bad if you get angry, or are in denial, that's a normal response. In my area there is a wonderful group that I connected with that we meet once a month and share news about research we have found, diet, PT, anything. It’s great because we all understand where we are coming from without having to explain.
Parkinsons is hard but you don't have to travel that road alone even if you have family at home who help you.
Gaining Ground: The Pursuit of Improving and Introducing New Parkinson’s Medications
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.
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 includeGLP-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.
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.”
Parkinson’s Foundation Genetics Study to Launch in 10 Latin American Countries
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.
My name is DawnElla Rust, and basketball was my first love. Though not a top-tier player like Caitlin Clark, I earned a scholarship for three years in college. I enjoyed training and knew my body well. After basketball, I stayed active with running, walking, weightlifting, hiking and rafting, while earning a Doctor of Education in Health Promotions and working as a university professor. My third love was teaching health in higher education, with my second love being my marriage in 1990.
In 2010, I became interim chair of my department, a role I hated and which brought significant stress. Notable stress symptoms included my right arm not swinging when I walked, difficulty fastening seat belts, lack of blinking, hand tremors, an unexplained Achilles issue and increased anxiety. The body that I knew well was not working. Collectively, these symptoms led to a Parkinson's disease (PD) diagnosis, which shocked me.
I found a wealth of information on medication selection, dosage, timing, drug interactions and side effects. I was encouraged by the few articles discussing the positive impact of exercise, although most never went beyond the old Nike commercial of “Just Do It!” The same generalities appeared in most diet advice, though it was often contradictory.
I knew nothing about Parkinson’s. Naively I even told a friend “Give me a couple of weeks and I will have this Parkinson’s thing figured out.” Initially, I believed I could quickly manage Parkinson's, but 15 years later, “I’m still figuring it out.”
I am better today thanks to invaluable resources from the Parkinson’s Foundation. One valuable resource is their trained professionals who offer phone support, especially on difficult days — and there are difficult days. I often use these Parkinson’s Foundation resources in an educational approach to openly discuss my diagnosis, because a teacher always teaches!
We’re here for you.
For answers to your Parkinson’s questions, call or email our Helpline. 1-800-4PD-INFO (1-800-473-4636)
As a university health professor, I was able to educate others on managing chronic diseases such as Parkinson’s disease. I taught a course on Social and Emotional Health, emphasizing the impact of social connections and emotions on physical well-being. The Parkinson’s Foundation's mission, "Better Lives. Together.", aligns with the principles I have taught and lived by.
Teaching concepts related to happiness, gratitude, humor and awe has empowered me to maintain a positive quality of life despite my diagnosis. Student feedback indicated that my personal narrative significantly contributed to their understanding of living well.
"The health philosophy I advocate is one where individuals strive to live well in the face of illness, disability and trauma."
Life inevitably presents challenges, such as the loss of loved ones, catastrophic events and diagnoses like Parkinson’s. I retired in 2024 after 30 years in higher education due to non-movement symptoms affecting my teaching, but I continue to educate and live a fulfilling life in retirement.
