Investigación

Investigación enfermedad de Parkinson, artículos, publicaciones científicas y noticias

Un estudio demuestra que un fármaco puede frenar el avance del párkinson

el . Publicado en Investigación Parkinson

La investigación, en la que ha participado el hospital Clínico, siguió a 1.176 pacientes de 14 países y constató que el Azilect retrasa la progresión de la enfermedad, aunque no la cura.

LARA COTERA. Zaragoza
Aún no se puede curar la enfermedad de Parkinson, pero es posible frenar su avance. Un estudio en el que han participado 1.176 pacientes de 129 hospitales, uno de ellos el Clínico Universitario Lozano Blesa, ha demostrado que un fármaco llamado Azilect, cuyo principio activo es la rasagilina, puede retrasar la progresión de este mal.
Las conclusiones detalladas de este importantísimo avance para 4 millones de pacientes en el mundo y más de 2.000 en Aragón se presentarán el próximo 26 de agosto en Madrid en el XII Congreso de la European Federation of Neurological Societies (EFN). No obstante, los coordinadores principales del estudio ya han comunicado a los investigadores de los centros sanitarios participantes (ubicados en 14 países diferentes) que se ha constatado que el medicamento es eficaz.
El neurólogo e investigador del Hospital Clínico Lozano Blesa, Javier López del Val, ha sido uno de los receptores de la noticia, que abre un campo de oportunidades para los afectados y, en especial, para quienes sufren la enfermedad en un estadio inicial.
"Es una noticia extraordinaria. No sabemos todavía cuál es el origen exacto del párkinson. Sí que conocemos que pueden influir la genética o los tóxicos ambientales, y por eso dar con un remedio que frene su avance es lo que llevamos años buscando", explica López del Val.

Proyecto ADAGIO

El Azilect es un fármaco de la empresa Teva Pharmaceutical Industries Ltd. Hace tiempo que se utiliza en pacientes de párkinson, aunque no para este fin. En principio, nació como un amplificador de la eficacia del tratamiento principal con dopamina, ya que mejoraba los síntomas.
Fue después cuando se impulsó el proyecto ADAGIO (Atenuation of Disease progression with Azilect Given Once Daily). Se trata de un estudio que ha seguido a dos grupos de pacientes, todos ellos precoces y no tratados.
A un primer grupo se le empezó a tratar de manera temprana, dándoles 1 miligramo o 2 al día durante 72 semanas. El otro sistema, de inicio tardío, consistía en que el segundo grupo tomara placebo durante 36 semanas y, después, ingiriese durante otras tantas semanas rasagilina a diario (entre 1 y 2 mg). El estudio concluyó hace cuatro meses y desde entonces se han estado analizando los resultados.
"Con los pacientes que participaban desde el Clínico nos dimos cuenta enseguida de que unos evolucionaban mucho mejor que otros", recuerda el doctor López del Val. "Es de esas ocasiones en las que lo notas, sabes que algo está funcionando de verdad", añade.
El fármaco está en el mercado y otro de los puntos más positivos que ha desvelado la investigación es que se ha demostrado que no tiene casi efectos secundarios. "Es decir, nuestros pacientes tienen mucho que ganar y muy poco que perder. No logramos que los síntomas regresen, pero sí que se mantengan", explica.
Por eso, las principales beneficiadas van a ser aquellas personas a los que se les acabe de diagnosticar y la enfermedad aún no les haya causado mermas considerables.
López del Val celebra además este nuevo paso en la lucha contra el párkinson. "Hace 26 años, los pacientes a los que llevabamos tratando 6 o 8 años estaban muy deteriorados. Ahora, por ejemplo, hay personas a las que las diagnosticamos hace 20 años y están en disposición de seguir luchando contra este mal en buenas condiciones", concreta.
El párkinson es un trastorno cerebral progresivo que causa temblores, lentitud de movimientos y rigidez muscular. En estos pacientes, las células que producen la dopamina empiezan a morir, algo trágico, porque precisamente la dopamina actúa como neurotransmisor. Es decir, es una sustancia química que permite a las células nerviosas comunicarse entre sí. Cuando estas fallan, los pacientes pierden la capacidad de controlar sus movimientos.
Sin embargo, la rasagilina es un inhibidor que bloquea la monoaminooxiadasa B, una enzima que degrada la dopamina. Los pacientes que la toman consiguen que aumente la concentración de dopamina en el cerebro y vuelvan a dominar sus movimientos.

Hsp104 antagonizes α-synuclein aggregation and reduces dopaminergic degeneration in a rat model of Parkinson disease

el . Publicado en Investigación Parkinson

Parkinson disease (PD) is characterized by dopaminergic neurodegeneration and intracellular inclusions of α-synuclein amyloid fibers, which are stable and difficult to dissolve. Whether inclusions are neuroprotective or pathological remains controversial, because prefibrillar oligomers may be more toxic than amyloid inclusions. Thus, whether therapies should target inclusions, preamyloid oligomers, or both is a critically important issue. In yeast, the protein-remodeling factor Hsp104 cooperates with Hsp70 and Hsp40 to dissolve and reactivate aggregated proteins. Metazoans, however, have no Hsp104 ortholog. Here we introduced Hsp104 into a rat PD model. Remarkably, Hsp104 reduced formation of phosphorylated α-synuclein inclusions and prevented nigrostriatal dopaminergic neurodegeneration induced by PD-linked α-synuclein (A30P). An in vitro assay employing pure proteins revealed that Hsp104 prevented fibrillization of α-synuclein and PD-linked variants (A30P, A53T, E46K). Hsp104 coupled ATP hydrolysis to the disassembly of preamyloid oligomers and amyloid fibers composed of α-synuclein. Furthermore, the mammalian Hsp70 and Hsp40 chaperones, Hsc70 and Hdj2, enhanced α-synuclein fiber disassembly by Hsp104. Hsp104 likely protects dopaminergic neurons by antagonizing toxic α-synuclein assemblies and might have therapeutic potential for PD and other neurodegenerative amyloidoses.

Articulo completo

New insight into what freezes Parkinson's patients and drives drug addicts

el . Publicado en Investigación Parkinson

 

CHICAGO -- Parkinson's disease and drug addiction are polar opposite diseases, but both depend upon dopamine in the brain. Parkinson's patients don't have enough of it; drug addicts get too much of it. Although the importance of dopamine in these disorders has been well known, the way it works has been a mystery.

New research from Northwestern University's Feinberg School of Medicine has revealed that dopamine strengthens and weakens the two primary circuits in the brain that control our behavior. This provides new insight into why a flood of dopamine can lead to compulsive, addictive behavior and too little dopamaine can leave Parkinson's patients frozen and unable to move.

"The study shows how dopamine shapes the two main circuits of the brain that control how we choose to act and what happens in these disease states, " said D. James Surmeier, lead author and the Nathan Smith Davis Professor and chair of physiology at the Feinberg School. The paper is published in the August 8 issue of the journal Science.

These two main brain circuits help us decide whether to act out a desire or not. For example, do you get off the couch and drive to the store for an icy six-pack of beer on a hot summer night, or just lay on the couch?

One circuit is a "stop" circuit that prevents you from acting on a desire; the other is a "go" circuit that provokes you to action. These circuits are located in the striatum, the region of the brain that translates thoughts into actions.

In the study, researchers examined the strength of synapses connecting the cerebral cortex, the region of the brain involved in perceptions, feelings and thought, to the striatum, home of the stop and go circuits that select or prevent action.

Scientists electrically activated the cortical fibers to simulate movement commands and boosted the natural level of dopamine. What happened next surprised them. The cortical synapses connecting to the "go" circuit became stronger and more powerful. At the same time, dopamine weakened the cortical connections in the "stop" circuit.

"This could be what underlies addiction," Surmeier said. "Dopamine released by drugs leads to abnormal strengthening of the cortical synapses driving the striatal 'go' circuits, while weakening synapses at opposing 'stop' circuits. As a result, when events associated with drug taking – where you took the drug, what you were feeling – occur, there is an uncontrollable drive to go and seek drugs."

"All of our actions in a healthy brain are balanced by the urge to do something and the urge to stop," Surmeier said. "Our work suggests that it is not just the strengthening of the brain circuits helping select actions that is critical to dopamine's effects, it is the weakening of the connections that enable us to stop as well. "

In the second part of the experiment, scientists created an animal model of Parkinson's disease by killing dopamine neurons. Then they looked at what happened when they simulated cortical commands to move. The result: the connections in the "stop" circuit were strengthened, and the connections in the "go" circuit were weakened.

"The study illuminates why Parkinson's patients have trouble performing everyday tasks like reaching across a table to pick up a glass of water when they are thirsty," Surmeier said.

Surmeier explained the phenomenon using the analogy of a car. "Our study suggests that the inability to move in Parkinson's disease is not a passive process like a car running out of gas," he said. "Rather, the car doesn't' move because your foot is jammed down on the brake. Dopamine normally helps you adjust the pressure on the brake and gas pedals. It helps you learn that when you see a red light at an intersection, you brake and when the green light comes on, you take your foot off the brake and depress the gas pedal to go. Parkinson's disease patients, who have lost the neurons that release dopamine, have their foot perpetually stuck on the brake."

Understanding the basis for these changes in brain circuitry moves scientists closer to new therapeutic strategies for controlling these brain disorders and other involving dopamine like schizophrenia, Tourette's syndrome and dystonia.

Contact: Marla Paul
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312-503-8928
Northwestern University

De la piel del enfermo a modelos de investigación en el laboratorio

el . Publicado en Investigación Parkinson

 

Actualizado jueves 07/08/2008 20:22 (CET)

ÁNGELES LÓPEZ

MADRID.- Son sólo unas células recogidas de la piel de unos pocos pacientes. Sin embargo, gracias a que han sido reprogramadas para devolverlas a un estadio primitivo, similar al de las células madre embrionarias, podrán utilizarse como modelo de estudio de 10 enfermedades genéticas como el síndrome de Down o el Parkinson.

Durante años, los investigadores han cultivado células humanas en el laboratorio para intentar imitar diferentes enfermedades genéticas, pero las técnicas disponibles presentaban defectos significativos. Las células que se obtenían de los pacientes tienen una vida muy limitada, lo que reduce el tipo de investigación con ellas. Por eso, en muchas ocasiones se recurre a experimentos con animales, como los ratones. Sin embargo, la fisiología de estos roedores y otros modelos con seres vivos no siempre se corresponde con la humana y no sirve para estudiar ciertos trastornos.

Hace unas semanas, investigadores estadounidenses mostraban cómo, por primera vez, habían conseguido neuronas a partir de células de la piel de una paciente con esclerosis lateral amiotrófica. Como explicaban esos expertos, la enfermedad podría estudiarse mejor al contar con neuronas que, genéticamente, estaban predestinadas a desarrollar ese trastorno. Así, se puede ver la evolución de estas células en una placa de laboratorio.

Algo parecido es lo que ha conseguido un grupo de científicos dirigidos por George Q. Daley, del Howard Hughes Medical Institute, y cuyos datos publica la revista 'Cell'. Estos expertos consiguieron células de la piel de nueve personas y de la médula de otro sujeto, para posteriormente reprogramarlas, con la técnica de Yamanaka, y obtener líneas celulares similares a las células madre embrionarias (iPS, siglas en inglés). Todos los participantes, cuya edad oscilaba entre el mes y los 57 años, presentaban una enfermedad originada por una alteración genética.

Herramienta de investigación

"Queríamos producir un gran número de modelos de enfermedades para nosotros, nuestros colaboradores y la comunidad científica que trabaja con células madre con el objetivo de acelerar la investigación", explica Daley. "Estas nuevas líneas son herramientas muy valiosas porque abordan el origen de las enfermedades. Nuestro trabajo es sólo el comienzo para el estudio de miles de patologías en una placa de Petri", declara.

Mediante la inserción de cuatro factores de crecimiento, los investigadores lograron reprogramar las células adultas y convertirlas en células 'bebé' capaces de convertirse en cualquier otro tipo de células. De esta manera, consiguieron 20 líneas (cultivos de células) pluripotentes pero con los mismos errores genéticos que contribuyeron a que cada uno de los pacientes desarrollara una de las siguientes enfermedades: Parkinson, diabetes tipo 1, enfermedad de Huntington, síndrome de Down, inmunodeficiencia combinada severa (niños 'burbuja'), síndrome de Lesch-Nyhan, enfermedad de Gaucher, síndrome de Shwachman-Diamons y dos formas de distrofia muscular.

"La falta de modelos accesibles de tejidos normales y patológicos ha hecho que muchas e importantes cuestiones sobre el desarrollo humano y la patogénesis [causa y formación] de enfermedades sean inaccesibles", explican los autores. El trabajo de ahora, la obtención de líneas celulares pluripotentes de pacientes con trastornos de un único gen, "nos permitirá conseguir modelos de miles de patologías utilizando las técnicas clásicas de cultivos celulares, y es una oportunidad para reparar los defectos genéticos".

El Instituto Harvard Stem Cell (IHSC) ha puesto en marcha una serie de recursos para establecer un centro en el que producir líneas celulares específicas de una enfermedad, con el propósito de ponerlas a disposición de la comunidad biomédica para su investigación. "Tenemos buenas razones para pensar que será posible encontrar nuevos tratamientos, y finalmente fármacos, para retrasar o incluso parar el curso de una serie de patologías. En los próximos años, este estudio será visto como una puerta abierta a una nueva forma de desarrollar terapias", explica Doug Melton del IHSC.

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Molecular Biometrics Announces Results of Parkinson's Disease Research and Receipt of Grant From Michael J. Fox Foundation to Advance Diagnostic Technology

el . Publicado en Investigación Parkinson

Molecular Biometrics Announces Results of Parkinson's Disease Research and Receipt of Grant From Michael J. Fox Foundation to Advance Diagnostic Technology
Tuesday August 5, 10:44 am ET

New research demonstrates proof-of-concept for diagnosing Parkinson's disease using non-invasive, biospectroscopy technology

Michael J. Fox Foundation awards grant to Molecular Biometrics for further development of Parkinson's diagnostic

CHESTER, N.J. and MONTREAL, Aug. 5 /PRNewswire/ -- A study published in the June issue of the peer-reviewed journal, Biomarkers in Medicine, demonstrated proof-of-concept for the use of a minimally-invasive technology being developed by Molecular Biometrics, LLC, to diagnose Parkinson's disease (PD). In the study, researchers used spectroscopy to develop a metabolic profile (or chemical signatures) of biological markers for PD. There is currently no definitive laboratory diagnostic for Parkinson's disease.

The company also announced receipt of an award from The Michael J. Fox Foundation for Parkinson's Research supporting further development of its technology platform to validate its PD diagnostic methodology.

"The lack of an objective biomarker to aid diagnosis and therapeutics development is one of the single greatest challenges facing the Parkinson's research field," said Katie Hood, CEO of The Michael J. Fox Foundation. "We are enthusiastic about helping to keep Molecular Biometrics' novel metabolomic diagnostic technology moving forward toward validation and clinical testing."

Researchers at Molecular Biometrics, Lady Davis Institute (LDI), Sir Mortimer B. Davis - Jewish General Hospital and McGill University have shown that, using biospectroscopy methods to create a specific biomarker profile, they can distinguish idiopathic Parkinson's disease from normal aging and other neurodegenerative conditions. Diagnosis of PD is currently based solely on a patient's medical history and neurological examination, making Parkinson's difficult to diagnose, particularly during early stages of the disease.

"We created a biomarker profile, using biospectroscopy techniques, to delineate a chemical signature in blood that identifies patients with Parkinson's disease," said Hyman M. Schipper, MD, PhD, FRCPC, lead author of the study and member of the Faculty of Medicine, Department of Neurology and Neurosurgery, and Department of Medicine, McGill University, and member of the Attending Staff in Neurology at Sir Mortimer B. Davis - Jewish General Hospital, in Montreal, Canada. "This proof-of-concept gives us great hope that biospectroscopy will offer a new approach to the early diagnosis of Parkinson's disease and other neurodegenerative disorders." Dr Schipper is a noted expert in brain aging and neurodegeneration, and a Founding Scientist and Medical Director (Neurosciences) at Molecular Biometrics.

In the study, fifty-two patients, 20 with mild or moderate stages of Parkinson's disease and 32 age-matched control subjects were recruited at the Jewish General Hospital. Whole blood samples were analyzed using near- infrared (NIR) spectroscopy and Raman spectroscopy (RS) methods which have previously been used to create metabolomic profiles (chemical signatures) of human biofluids, including serum and whole blood.

Both NIR and RS methods were applied to measure the degree of oxidative stress (OS) present in each sample. OS has been considered to be a potential biomarker for Parkinson's disease. However, to date, chemical markers have not proven sufficiently robust to serve as an accurate or reliable biomarker of the disease. OS is caused by a chemical imbalance that can damage critical components of a cell, including proteins, lipids and DNA. OS is known to be involved in many diseases, including PD and Alzheimer's disease. The data from this study showed that the two independent biospectroscopy measurement techniques yielded similar and consistent results. In differentiating Parkinson's disease patients from the control group, RS achieved a sensitivity of 74% and specificity of 72%, with eight false positives and four false negatives. NIR achieved a sensitivity of 74% and specificity of 76%, with four false positives and five false negatives.

"We are greatly encouraged by these results and will continue our research and development efforts to further explore the application of our proprietary technology in the development of an accurate, minimally invasive and cost- effective diagnostic tool for Parkinson's disease," added James T. Posillico, PhD, President and Chief Executive Officer, Molecular Biometrics.

"Spectroscopy of human plasma for diagnosis of idiopathic Parkinson disease," was published in Biomarkers in Medicine (June 2008, Vol. 2, No. 3, Pages 229-238).

Molecular Biometrics was one of six industry research teams to receive a total of $2.7 million in funding granted under The Michael J. Fox Foundation's Therapeutics Development Initiative (TDI) program. TDI is the cornerstone of the Foundation's venture philanthropy efforts to help push promising candidate therapeutics forward in industry pipelines by allowing the Foundation to share the risk of product development.

"We are honored to be a grant recipient of The Michael J. Fox Foundation, and are excited to have our technology recognized for its potential to positively impact the future of PD diagnosis and treatment," said Posillico.

About Parkinson's Disease

Parkinson's disease is a chronic, degenerative neurological disorder that affects one in 100 people over age 60. This degenerative disorder of the central nervous system often affects motor skills and speech, as well as other functions, and is characterized by muscle rigidity, tremor, a slowing of physical movement and, in extreme cases, a loss of physical movement. Parkinson's disease belongs to a group of conditions called movement disorders. While the average age at onset is 60, disease onset starts by age 40 in an estimated five to 10 percent of patients, and people as young as 30 can also be affected. It is estimated that at least one million people in the United States, and six million worldwide, have Parkinson's disease.

About Metabolomics

Metabolomics is a complex scientific process that identifies and measures individual signals from many molecular compounds produced by cellular metabolism which, when evaluated as a whole, represent unique biomarkers of biologic function in health and disease.

Molecular Biometrics uses near infrared (NIR) biospectroscopy in its metabolomic applications. NIR is a robust platform that rapidly measures the vibrational energy absorbed by molecular functional groups, creating a profile of molecules that are descriptive of cellular function.

The spectral signatures are further analyzed by proprietary bioinformatics and chemometrics that result in the creation of a novel "metabolomic profile" or "fingerprint" that can be used to distinguish systematically between the often subtle differences that separate normal physiology from the onset or progression of disease, or an individual's response to therapeutic intervention. Metabolomics is commonly used in pharmaceutical research, molecular diagnostics and food and agrichemical industries.

About The Michael J. Fox Foundation

Founded in 2000, The Michael J. Fox Foundation for Parkinson's Research is dedicated to ensuring the development of a cure for Parkinson's disease within the coming decade through an aggressively funded research agenda. The Foundation has funded approximately $126 million in research to date. For more information, please visit www.michaeljfox.org.

About Molecular Biometrics

Molecular Biometrics, LLC, is applying novel metabolomic technologies to develop accurate, non-invasive clinical tools for use in personalized medicine to evaluate normal biologic function in health and in disease, and for drug discovery and development. The company's proprietary technology is being applied in reproductive health and IVF, neurodegenerative disease (e.g., Alzheimer's disease and Parkinson's disease), maternal fetal medicine, pulmonary metabolism and edema, and lactate metabolism. Molecular Biometrics is privately held and headquartered in Chester, NJ, with research and development facilities in New Haven, CT, and Montreal, Quebec. For more information, please visit www.molecularbiometrics.com.


Source: Molecular Biometrics

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