La revista 'The Lancet' publica una revisión de los estudios publicados hasta la fecha sobre las nuevas terapias que se han empezado a utilizar contra la artritis reumatoide. Según este informe, los últimos fármacos desarrollados han abierto el abanico de posibilidades a los pacientes. Sin embargo, todavía son necesarias más investigaciones que por un lado analicen los efectos secundarios a largo plazo de estos tratamientos y por otro aporten nuevas dianas en la lucha contra esta enfermedad.
Todavía no se conoce la causa que origina la artritis reumatoide. Se sabe que la enfermedad está relacionada con una activación excesiva del sistema inmunológico, que genera una producción de sustancias que inducen a la inflamación y destrucción del hueso de las articulaciones.
En los últimos años, se han desarrollado tres tipos de fármacos biológicos que van dirigidos a ciertas moléculas (antígenos) presentes en las células del sistema inmunológico o a proteínas producidas por ellas: abatacept, rituximab y tocilizumab. Los dos primeros ya han sido aprobados por las autoridades sanitarias de Estados Unidos y Europa (la FDA y la EMEA), el tercero se encuentra en fase III de investigación y todavía no se ha comercializado.
Abatacept actúa bloqueando dos moléculas, la CD80 o la CD86, que estimulan la activación de los linfocitos T (células del sistema inmunológico), mientras que rituximab actúa contra el antígeno CD20 que reduce los linfocitos B y tocilizumab bloquea la acción de la interleuquina 6, un tipo de proteínas que activa los linfocitos T y B.
Según la revisión, realizada por reumatólogos de Universidad de Viena, del Hospital Hietzing, también en Viena (Austria), del Centro Médico Cedars-Sinai de Los Ángeles, California (EEUU) y del Chapel Allerton Hospital en Leeds (Reino Unido), para considerar si estos fármacos son eficaces se debe alcanzar una máxima respuesta clínica y una reducción en la actividad de la enfermedad.
Y eso es lo que se ha valorado en los diferentes estudios realizados hasta la fecha. Los ensayos que evaluaron rituximab muestran que redujo en más de un 50% los síntomas de la artritis reumatoide en un tercio de los pacientes en los que se probó la terapia.
En cuanto a los efectos secundarios detectados, la revisión señala reacciones tras la infusión del medicamento en el 30-35% de los participantes. También se registraron infecciones más graves en las personas tratadas con rituximab que en aquellas que había recibido placebo. Además, la actividad sobre los linfocitos B disminuye con el tiempo por lo que se requiere volver a tratar a los pacientes para mantener su eficacia.
Eficacia y efectos secundarios
Una terapia combinada de metotrexato y 10mg de abatacept logró a los seis meses una mejoría del 50% de los síntomas de la artritis reumatoide en el 40% de los pacientes. Además, se detectó una mejoría mediante pruebas radiográficas. Los efectos secundarios más frecuentes han sido cefalea, nasofaringitis, mareos e hipertensión, sobre todo durante la primera hora tras su administración. Trastornos como neumonía, celulitis, diverticulitis o infecciones urinarias también aparecieron con más frecuencia con este fármaco.
No se recomienda la combinación de abatacept con los antiTNF ni con otros agentes biológicos debido a que la aparición de efectos secundarios se multiplica y a que no se mejora la eficacia del tratamiento.
Estudios en laboratorio y con animales observaron que el bloqueo de la interleuquina 6 prevenía la formación de osteoclastos, células que destruyen el hueso. Tocilizumab, que actúa inhibiendo esta proteína, combinado con metotrexato reduce en un 50% los síntomas de la artritis reumatoide en más de un 40% de los pacientes. Esta terapia generó en un pequeño porcentaje de los pacientes cefalea, erupciones en la piel y fiebre. También se detectó un aumento de los niveles de colesterol y de enzimas hepáticas.
Cuanto antes, mejor
Estas terapias podrían utilizarse principalmente en pacientes que presentan síntomas de artritis reumatoide a pesar de estar utilizando inhibidores del factor de nectrosis tumoral (los antiTNF) y metotrexato, que constituyen la terapia clásica y de inicio frente a la enfermedad.
El tratamiento debe comenzarse cuanto antes porque, tal y como indicaban recientemente reumatólogos españoles en el IV Simposio de Artritis Reumatoide, no tratar la enfermedad no sólo afectará a las articulaciones sino que conllevará complicaciones en otros órganos como el corazón.
"Los nuevos fármacos discutidos aquí [en la revisión] expanden claramente el número de terapias contra la artritis reumatoide. Sin embargo, más investigaciones serán necesarias como una comparación directa entre metotrexato y los inhibidores TNF", señalan los autores.
No obstante, los pacientes con artritis reumatoide verán a lo largo de los próximos meses y años los resultados de numerosos estudios que se están llevando a cabo evaluando nuevos fármacos como los que actúan frente a la interleuquina 1 beta, los nuevos inhibidores TNF o los agentes que interfieren únicamente en la activación del osteoclasto.
Qué fármacos deberán utilizarse primero o por qué los pacientes responden a un agente pero no a otro incluso cuando los tratamientos están dirigidos a la misma molécula, son preguntas que deberán contestarse en futuras investigaciones para las que se requerirán inversiones y dedicación, tal y como reclaman los autores de la revisión.
martes, 3 de noviembre de 2009
Nanotubes May Heal Broken Bones
Robert Haddon is director of the Center for Nanoscale Science and Engineering at the University of California at Riverside. View Slideshow Human bones can shatter in accidents, or they can disintegrate when ravaged by disease and time. But scientists may have a new weapon in the battle against forces that damage the human skeleton.
Carbon nanotubes, incredibly strong molecules just billionths of a meter wide, can function as scaffolds for bone regrowth, according to researchers led by Robert Haddon at the University of California at Riverside. They have found a way to create a stronger and safer frame than the artificial bone scaffolds currently in use.
Human bones are both organic and inorganic. The organic part is made of collagen, the most abundant protein in mammals. The inorganic component is hydroxyapatite, a type of calcium crystal. The collagen forms a sort of natural scaffold over which the calcium crystals organize into bone. The idea in Haddon's research is to use the nanotubes as substitutes for the collagen to promote new bone growth when bones have been broken or worn down.
Haddon and his team chemically treated carbon nanotubes to attract hydroxyapatite in work they published in the June 14 issue of Chemistry of Materials.
"This is nice work," said James Mitchell Tour, a chemistry professor at Rice University. "Anything you can do to take care of people's bones by augmenting the mineralization process is a big deal. It's really nice to see nanotubes being used to function like that."
Carbon nanotubes are an excellent choice for supporting bone, scientists say, because at the molecular scale they are the strongest human-made fiber in existence.
"The advantage of the carbon nanotube here is that at the molecular scale, it is the strongest fiber man will ever make," said Michael Strano, an assistant professor of chemical and biomolecular engineering at the University of Illinois at Urbana-Champaign. "The chemical bonds (in carbon nanotubes) are nature's strongest. Man cannot envision a molecule that will be stronger along its length."
Strano, an expert in carbon nanotube materials. believes the importance of the work stretches beyond bone scaffolds. Though the nanotubes were treated in this case to attract a mineral that might help grow and repair bones, Strano was excited by the possibility of treating the nanotubes in other ways so that they attract, grow and direct all sorts of minerals.
Haddon agreed that his team's biggest accomplishment was discovering how to get the carbon nanotubes to encourage the crystal calcium growth. "Pristine carbon nanotubes can not effectively serve as the nucleus for the growth of hydroxyapatite," he said. "When we tailored the properties of the nanotubes through chemistry, we were able to grow the hydroxyapatite. This result reinforces our belief that, for many applications, nanotube properties have to be tailored through chemistry."
Haddon hopes soon to test how the human body will respond to carbon nanotubes. Even though humans are carbon-based, that's not an iron-clad guarantee that the two will get along smoothly.
Other major questions need to be answered as well. The nanotube solution would likely be injected as a liquid at the site of bone trauma or degradation. Researchers aren't sure if it will know how to organize itself and facilitate growth of the right amount of bone in the right place. It's also possible the nanotube-enhanced bone could be too strong for the surrounding bones and damage the un-enhanced bones, similar to the way a diamond rubbing against copper would eventually degrade the copper.
Nanotube researchers tend to be engineers and material chemists, not experts in tissue engineering. So collaboration between the chemists and bioengineering experts is essential. Tour has established such a partnership with Antonios Mikos, a bioengineering professor at Rice. Together they are researching ways to use nanotubes to strengthen the artificial polymer scaffolds currently in use to repair shattered bones. Tour said they have found that a polymer scaffold composed of just 0.1 percent nanotubes (by weight) has roughly double the structural integrity of a polymer alone.
"Nanotubes are already a big deal in the rubber and elastomer industries," Tour said. "It's going to be a big deal in the medical industry. When we talk about enhancing rigidity in the medical field, one immediately thinks of bones. That's a good place to start."
Carbon nanotubes, incredibly strong molecules just billionths of a meter wide, can function as scaffolds for bone regrowth, according to researchers led by Robert Haddon at the University of California at Riverside. They have found a way to create a stronger and safer frame than the artificial bone scaffolds currently in use.
Human bones are both organic and inorganic. The organic part is made of collagen, the most abundant protein in mammals. The inorganic component is hydroxyapatite, a type of calcium crystal. The collagen forms a sort of natural scaffold over which the calcium crystals organize into bone. The idea in Haddon's research is to use the nanotubes as substitutes for the collagen to promote new bone growth when bones have been broken or worn down.
Haddon and his team chemically treated carbon nanotubes to attract hydroxyapatite in work they published in the June 14 issue of Chemistry of Materials.
"This is nice work," said James Mitchell Tour, a chemistry professor at Rice University. "Anything you can do to take care of people's bones by augmenting the mineralization process is a big deal. It's really nice to see nanotubes being used to function like that."
Carbon nanotubes are an excellent choice for supporting bone, scientists say, because at the molecular scale they are the strongest human-made fiber in existence.
"The advantage of the carbon nanotube here is that at the molecular scale, it is the strongest fiber man will ever make," said Michael Strano, an assistant professor of chemical and biomolecular engineering at the University of Illinois at Urbana-Champaign. "The chemical bonds (in carbon nanotubes) are nature's strongest. Man cannot envision a molecule that will be stronger along its length."
Strano, an expert in carbon nanotube materials. believes the importance of the work stretches beyond bone scaffolds. Though the nanotubes were treated in this case to attract a mineral that might help grow and repair bones, Strano was excited by the possibility of treating the nanotubes in other ways so that they attract, grow and direct all sorts of minerals.
Haddon agreed that his team's biggest accomplishment was discovering how to get the carbon nanotubes to encourage the crystal calcium growth. "Pristine carbon nanotubes can not effectively serve as the nucleus for the growth of hydroxyapatite," he said. "When we tailored the properties of the nanotubes through chemistry, we were able to grow the hydroxyapatite. This result reinforces our belief that, for many applications, nanotube properties have to be tailored through chemistry."
Haddon hopes soon to test how the human body will respond to carbon nanotubes. Even though humans are carbon-based, that's not an iron-clad guarantee that the two will get along smoothly.
Other major questions need to be answered as well. The nanotube solution would likely be injected as a liquid at the site of bone trauma or degradation. Researchers aren't sure if it will know how to organize itself and facilitate growth of the right amount of bone in the right place. It's also possible the nanotube-enhanced bone could be too strong for the surrounding bones and damage the un-enhanced bones, similar to the way a diamond rubbing against copper would eventually degrade the copper.
Nanotube researchers tend to be engineers and material chemists, not experts in tissue engineering. So collaboration between the chemists and bioengineering experts is essential. Tour has established such a partnership with Antonios Mikos, a bioengineering professor at Rice. Together they are researching ways to use nanotubes to strengthen the artificial polymer scaffolds currently in use to repair shattered bones. Tour said they have found that a polymer scaffold composed of just 0.1 percent nanotubes (by weight) has roughly double the structural integrity of a polymer alone.
"Nanotubes are already a big deal in the rubber and elastomer industries," Tour said. "It's going to be a big deal in the medical industry. When we talk about enhancing rigidity in the medical field, one immediately thinks of bones. That's a good place to start."
Suscribirse a:
Entradas (Atom)
