Neurologist Prof. José Obeso has built a large research and clinical practice centered on using focused ultrasound to halt the progression of Parkinson’s and other brain diseases.
After learning about focused ultrasound in an airport lobby from a fellow Spaniard, Toronto neurosurgeon Andres Lozano in 2014, Prof. José Obeso’s career took on a whole new focus. As a neurologist, he was always interested in helping patients suffering from neurodegenerative disorders.
In the past six years, he has built a large research and clinical practice centered on using focused ultrasound to halt the progression of Parkinson’s and other brain diseases. We interviewed Prof. Obeso to learn more about the Centro Integral de Neurociencias (HM CINAC) and his ongoing work, which has been published in journals such as Lancet Neurology.
Focused Ultrasound Work
When and how did you get interested in focused ultrasound?
I heard about focused ultrasound from Dr. Andres Lozano, a renowned functional neurosurgeon from Toronto. He alerted me about this technology in 2014, when we ran into each other in the lobby of an airport in Germany.
What are your areas of interest in focused ultrasound?
We are dedicated to halting the Parkinson’s disease neurodegeneration process and to expanding that concept to other neurodegenerative diseases. Focused ultrasound offers a good opportunity to greatly contribute toward this goal.
What mechanisms and clinical indications do you study?
We study abnormal neuronal activity in brain circuits that underlie movement disorders such as in Parkinson's disease, essential tremor, dyskinesias, and others. More fundamentally, we are interested in the mechanisms of neuronal vulnerability of the dopaminergic system in Parkinson's disease and how to modify disease progression.
What is the goal of your work?
The goal of our work is to stop neurodegeneration.
What are your funding sources?
Our funding comes from various, but limited, sources. Last year, our research support came from the Spanish public system (about 40 percent), donations (about 30 percent), and our own institution and commercial deliverables (30 percent). The Focused Ultrasound Foundation helped to provide funding for our Parkinson’s subthalamic nucleus (STN) clinical trial.
Who are your team members?
We have a fairly large team of more than 40 people, including neurologists, neuropsychologists, nurses, neurosurgeons, biologists, engineers, physicists, neurophysiologists, animal care experts, technicians, and a wide range of students.
I serve as HM CINAC’s director and provide neurology care. Cristina Calvo is the Director´s Secretary and Ainhoa Marcos is the Director´s Assistant. Frida Hernández is our research nurse.
Our neurologists are Raúl Martínez, Michele Matarazzo, Carmen Gasca, Álvaro Sánchez-Ferro, Lydia Álvarez, and Fernando Alonso, who is also a neurophysiologist. Mariana Hernández is a neurologist who is completing her postdoctoral fellowship, and our predoctoral neurology fellows are Jorge Máñez and Beatriz Fernández.
Our neurosurgeons are Marta del Álamo and Diego Medina.
Along with Dr. Alonso, Guglielmo Foffani is a neurophysiologist who is also a biomedical engineer. Our postdoctoral neurophysiologists are Claudia Ammann, Desiré Humanes, and Josefa Zaldívar-Díez. Cristina Pagge is a predoctoral neurophysiologist.
We have a principal cognitive neuroscientist, Ignacio Obeso, trained as a neuropsychologist. Our predoctoral neuropsychologists are David Mata and Pasqualina Guida.
Our neurophysiologists for animal models are Inés Trigo Damas (primate behavior), Ledia F. Fernández (rodent behavior), and Yaiza Varn Waes (PhD student, rodent behavior). F. Javier Blesa provides histochemistry and cell biology for animal models, and Tiziano Balzano is a postdoctoral histologist.
In neuroimaging, we have a physicist, Rafael Rodríguez Rojas, and an engineer, Jose Ángel Pineda. They are joined by three PhD students: Miguel López (physicist) and Jesús Pardo and Jaime Caballero (engineers).
Our laboratory technicians are Raquel Márquez, Beatriz Pro, and Maria Ciorraga. Our veterinarian is Sergio Ferreiro, and our animal care technicians are Juan Antonio Santos, Cristina Gil, and Jennifer Ribeiro.
Three additional PhD students are Natalia López (cell vulnerability), Iván Castela (dyskinesia models), and Alejandro Reinares (non-human primate neurophysiology).
Who are your internal and external collaborators?
We are pleased to collaborate with many great individuals at the following worldwide organizations:
- First of all, we are part of Ciberned - ISCIII, a publicly sustained research network for studying neurodegeneration that allows us to work with various high-level Spanish teams.
- Dpto. Anatomía, Histología y Neurociencia (Prof. Carmen Cavada), Universidad Autónoma de Madrid, Madrid, Spain
- Instituto Cajal (Dr. R. Moratalla), Spanish National Research Council (CSIC), Madrid, Spain
- Dpto. de Anatomia (Profesora M.T. Herrero), Universidad de Murcia, Murcia, Spain
- Achucarro Basque Center for Neuroscience, Laboratory of Neurobiology (Prof Carlos Matute), Universidad del País Vasco (UPV), Leioa, Spain
- Dpto. Fisiología, Facultad de Medicina, Universidad de la Laguna (Prof. M. Rodriguez), San Cristóbal de La Laguna, Santa Cruz de Tenerife, Spain
- Dpto. Physiopathologie des syndromes parkinsoniens (Prof. Erwan Bezard), Institute of Neurodegenerative Diseases, University Victor Segalen, Bordeaux, France
- Dpt. of Psychology (Prof. Peter Redgrave), Emeritus, the University of Sheffield, Sheffield, UK
- Champalimaud Neuroscience Program (Prof. Rui Costa), Champalimaud Foundation, Lisbon, Portugal
- Department of Neurological Sciences (Jeffrey H. Kordower), Rush University Medical Center, Chicago, IL, USA
- Espacio CISNe (Dr. Alejandro Rojas), Universidad Austral de Chile, Valdivia, Chile
- Primate Research Institute (Prof M. Takada, Dr. K. Inoue), Kyoto University, Kyoto, Japan
- Division of System Neurophysiology (Prof. A. Nambu), National Institute of Physiological Science, Okazaki, Japan
What are your greatest achievements? Any major disappointments?
Both are difficult questions to answer! For the former, I would say forming , developing, and now getting to consolidate Centro Integral de Neurociencias (CINAC), the clinical and research center that I have run in south Madrid since the fall of 2014. More concretely, it was an achievement to have completed a double-blind, randomized study to show that unilateral subthalamotomy (via focused ultrasound) improves the cardinal motor features of Parkinson´s disease. The publication of these data is now under second review in a major journal. For the latter, the tragedy of knowing how to foster progress in combating neurodegeneration but not having the appropriate funding to do so.
What do you see as impediments to your success?
A lack of adequate funding.
What is on your research wish list?
To succeed in our upcoming blood-brain barrier opening project, which will allow us to reach pilot trials in patients within the next two years.
Has the Foundation played a role in your work?
Yes, the Foundation helped us finalize a double-blind trial with focused ultrasound—mediated subthalamotomy in patients with Parkinson´s disease. Hopefully the Foundation will also support some of our preclinical research with BBB opening.
How many patients have you treated with focused ultrasound?
We have treated about 250 patients over the past 5 years.
Do you have a favorite clinical research story?
We treated for the first time a young woman with multiple sclerosis who had very severe right upper limb tremor as her only source of relevant disability. It was a difficult decision, because there was no previous experience, the possibility of disturbing the underlying disease process was a concern, and the tremor was so large and severe that we couldn´t be certain about the therapeutic outcome. However, the patient herself is an MD, and her parents are also physicians. So, my team and I discussed with them the benefit-to-risk ratio. The patient refused to have deep brain stimulation (DBS) treatment and finally we all agreed with focused ultrasound thalamotomy. The result was excellent, and the details were published last year by Mañez-Miro et al. in the journal Multiple Sclerosis.
Looking ahead, what comes next?
During 2020, we will conduct gene therapy research in a non-human primate model of Parkinson´s disease. This is a necessary step to move on toward a human clinical trial.
Foffani G, Trigo-Damas I, Pineda-Pardo JA, Blesa J, Rodríguez-Rojas R, Martínez-Fernández R, Obeso JA. Focused ultrasound in Parkinson’s disease: A twofold path toward disease modification. Mov Disord 2019 Sep;34(9):1262-1273. doi: 10.1002/mds.27805. Epub 2019 Aug 14.
Karakatsani ME, Blesa J, Konafagou EE. Blood-Brain Barrier Opening with Low Frequency Focused Ultrasound in Experimental Models of Parkinson's Disease. Mov Disord 2019 Sep;34(9):1252-1261. doi: 10.1002/mds.27804. Epub 2019 Jul 30.
Martinez-Fernandez R, Rodriguez-Rojas R, Del Alamo M, et al. Focused ultrasound subthalamotomy in patients with asymmetric Parkinson's disease: a pilot study. Lancet Neurol 2018;17(1):54-63. doi: undefined(17)30403-9.
Obeso JA, Stamelou M, Goetz CG, et al. Past, present, and future of Parkinson's disease: A special essay on the 200th Anniversary of the Shaking Palsy. Mov Disord 2017;32(9):1264-1310. doi: 10.1002/mds.27115.
Krack P, Martinez-Fernandez R, Del Alamo M, Obeso JA. Current applications and limitations of surgical treatments for movement disorders. Mov Disord 2017;32(1):36-52. doi: 10.1002/mds.26890.
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