One of the earliest known impairments caused by Alzheimer's disease -- loss of sense of smell -- can be restored by removing a plaque-forming protein in a mouse model of the disease, a study led by a Case Western Reserve University School of Medicine researcher finds. The study confirms that the protein, called amyloid beta, causes the loss.
"The evidence indicates we can use the sense of smell to determine if someone may get Alzheimer's disease, and use changes in sense of smell to begin treatments, instead of waiting until someone has issues learning and remembering," said Daniel Wesson, assistant professor of neuroscience at Case Western Reserve and lead investigator. "We can also use smell to see if therapies are working."
A description of the research is published in the Nov. 2 issue of The Journal of Neuroscience.
Smell loss can be caused by a number of ailments, exposures and injuries; but since the 1970s, it has been identified as an early sign of this disease. The new research shows how and where in the brain this happens, and that the impairment it can be treated.
"Understanding smell loss, we think, will hold some clues about how to slow down this disease," Wesson said.
There is currently no effective treatment or cure for the disease, marked by eroding senses, cognition and coordination, leading to death. Currently 5.3 million Americans suffer from Alzheimer's and the number is expected to triple to 16 million by 2050, according to the Alzheimer's Association.
Wesson worked with Anne H. Borkowski, a researcher at the Nathan S. Kline Institute in Orangeburg, N.Y., Gary E. Landreth, professor of neuroscience at Case Western Reserve School of Medicine, and Ralph A. Nixon, Efrat Levy and Donald A. Wilson, of the New York University School of Medicine.
They found that just a tiny amount of amyloid beta -- too little to be seen on today's brain scans -- causes smell loss in mouse models.
Amyloid beta plaque accumulated first in parts of the brain associated with smell, well before accumulating in areas associated with cognition and coordination.
Early on, the olfactory bulb, where odor information from the nose is processed, became hyperactive.
Over time, however, the level of amyloid beta increased in the olfactory bulb and the bulb became hypoactive. Despite spending more time sniffing, the mice failed to remember smells and became incapable of telling the difference between odors.
The same pattern is seen in people with the disease. They become unresponsive to smells as they age.
While losses in the olfactory system occurred, the rest of the mouse model brain, including the hippocampus, which is a center for memory, continued to act normally early in the disease stage.
"This shows the unique vulnerability of the olfactory system to the pathogenesis of Alzheimer's disease," Wesson said.
The team then sought to reverse the effects. Mice were given a synthetic liver x-receptor agonist, a drug that clears amyloid beta from the brain. After two weeks on the drug, the mice could process smells normally.
After withdrawal of the drug for one week, impairments returned.
Wesson and his team are now following-up on these discoveries to determine how amyloid spreads throughout the brain, to learn methods to slow disease progression.
**Source: Case Western Reserve University
01 December 2011
El momento clave de la enfermedad celiaca
Los especialistas calculan que el 1% de la población española padece enfermedad celiaca. Estas personas tienen una intolerancia permanente al gluten, que es una proteína presente en cereales como el trigo, el centeno o la cebada, entre otros, por lo que deben eliminar estos productos de su dieta para evitar complicaciones. Sin embargo, la gran mayoría de los enfermos desconoce que lo son.
"Sólo uno de cada seis o siete pacientes se diagnostica adecuadamente, por lo que muchos se pierden", ha explicado a ELMUNDO.es Eduardo Arranz, presidente de la Sociedad Española de Enfermedad Celiaca durante el simposio 'Soluciones emergentes para la Celiaquía' que ha organizado esta semana en Madrid la Fundación Ramón Areces y el Colegio Oficial de Químicos de Madrid.
Este encuentro, que ha reunido a los principales especialistas en la materia, ha servido de altavoz al Proyecto PACE (Proyecto de Ayuda a los Celiacos Españoles), una iniciativa que reclama esfuerzos para abordar la problemática de la enfermedad celiaca desde un punto de vista multidisciplinar, es decir, tanto desde la óptica de salud pública, y la mejora de la detección y los tratamientos, como desde la industria de fabricación de alimentos sin gluten, la detección de la proteína o la formación del profesorado escolar.
Uno de los principales mensajes que se han lanzado en el simposio hace hincapié en los importantes logros que en los últimos años se han logrado sobre el conocimiento de la enfermedad y las técnicas de diagnóstico disponibles. Sin embargo, expertos como Amado Salvador Peña, profesor emérito de la Universidad Medisch Centrum de Amsterdam (Holanda), también han subrayado la importancia de que estos logros se traduzcan pronto "en una mejor identificación de los casos" y en una uniformidad de los criterios empleados para la detección.
"Estamos en una encrucijada en cuanto que tenemos que saber cómo aunar todas las herramientas de las que disponemos para diagnosticar de una forma más eficaz", ha coincidido Arranz.
"Hay que valorar muy bien y hacer estudios que valoren el coste y la eficacia para encontrar esos pacientes que se escapan y cuya falta de diagnóstico está acarreando también gastos al sistema sanitario", ya que una enfermedad celiaca no detectada puede acarrear trastornos tan dispares como infertilidad, ataxias o depresión.
El gluten será sin, duda, un elemento clave a investigar en el futuro ya que, según ha explicado Arranz, cada vez hay más evidencias científicas de que esta proteína también puede causar síntomas gastrointestinales a personas que, en puridad, no son celiacos.
"En pruebas diagnósticas, como la serología, dan negativo y muchos tampoco tienen lesiones intestinales, pero vemos que cuando retiramos el gluten de su dieta experimentan una importante mejoría", señala. "Tenemos que estudiar a fondo esa sensibilidad y ver cómo debe ser el abordaje de estos pacientes", añade.
Según su punto de vista, para el futuro es fundamental seguir apuntalando la colaboración entre especialistas en la práctica clínica, genetistas, inmunólogos y tecnólogos de los alimentos, entre otros expertos.
**publicado en "EL MUNDO"
"Sólo uno de cada seis o siete pacientes se diagnostica adecuadamente, por lo que muchos se pierden", ha explicado a ELMUNDO.es Eduardo Arranz, presidente de la Sociedad Española de Enfermedad Celiaca durante el simposio 'Soluciones emergentes para la Celiaquía' que ha organizado esta semana en Madrid la Fundación Ramón Areces y el Colegio Oficial de Químicos de Madrid.
Este encuentro, que ha reunido a los principales especialistas en la materia, ha servido de altavoz al Proyecto PACE (Proyecto de Ayuda a los Celiacos Españoles), una iniciativa que reclama esfuerzos para abordar la problemática de la enfermedad celiaca desde un punto de vista multidisciplinar, es decir, tanto desde la óptica de salud pública, y la mejora de la detección y los tratamientos, como desde la industria de fabricación de alimentos sin gluten, la detección de la proteína o la formación del profesorado escolar.
Uno de los principales mensajes que se han lanzado en el simposio hace hincapié en los importantes logros que en los últimos años se han logrado sobre el conocimiento de la enfermedad y las técnicas de diagnóstico disponibles. Sin embargo, expertos como Amado Salvador Peña, profesor emérito de la Universidad Medisch Centrum de Amsterdam (Holanda), también han subrayado la importancia de que estos logros se traduzcan pronto "en una mejor identificación de los casos" y en una uniformidad de los criterios empleados para la detección.
"Estamos en una encrucijada en cuanto que tenemos que saber cómo aunar todas las herramientas de las que disponemos para diagnosticar de una forma más eficaz", ha coincidido Arranz.
"Hay que valorar muy bien y hacer estudios que valoren el coste y la eficacia para encontrar esos pacientes que se escapan y cuya falta de diagnóstico está acarreando también gastos al sistema sanitario", ya que una enfermedad celiaca no detectada puede acarrear trastornos tan dispares como infertilidad, ataxias o depresión.
El gluten será sin, duda, un elemento clave a investigar en el futuro ya que, según ha explicado Arranz, cada vez hay más evidencias científicas de que esta proteína también puede causar síntomas gastrointestinales a personas que, en puridad, no son celiacos.
"En pruebas diagnósticas, como la serología, dan negativo y muchos tampoco tienen lesiones intestinales, pero vemos que cuando retiramos el gluten de su dieta experimentan una importante mejoría", señala. "Tenemos que estudiar a fondo esa sensibilidad y ver cómo debe ser el abordaje de estos pacientes", añade.
Según su punto de vista, para el futuro es fundamental seguir apuntalando la colaboración entre especialistas en la práctica clínica, genetistas, inmunólogos y tecnólogos de los alimentos, entre otros expertos.
**publicado en "EL MUNDO"
Eating fish reduces risk of Alzheimer's disease
People who eat baked or broiled fish on a weekly basis may be improving their brain health and reducing their risk of developing mild cognitive impairment (MCI) and Alzheimer's disease, according to a study presented November 30 at the annual meeting of the Radiological Society of North America (RSNA). "This is the first study to establish a direct relationship between fish consumption, brain structure and Alzheimer's risk," said Cyrus Raji, M.D., Ph.D., from the University of Pittsburgh Medical Center and the University of Pittsburgh School of Medicine. "The results showed that people who consumed baked or broiled fish at least one time per week had better preservation of gray matter volume on MRI in brain areas at risk for Alzheimer's disease."
Alzheimer's disease is an incurable, progressive brain disease that slowly destroys memory and cognitive skills. According to the National Institute on Aging, as many as 5.1 million Americans may have Alzheimer's disease. In MCI, memory loss is present but to a lesser extent than in Alzheimer's disease. People with MCI often go on to develop Alzheimer's disease.
For the study, 260 cognitively normal individuals were selected from the Cardiovascular Health Study. Information on fish consumption was gathered using the National Cancer Institute Food Frequency Questionnaire. There were 163 patients who consumed fish on a weekly basis, and the majority ate fish one to four times per week. Each patient underwent 3-D volumetric MRI of the brain. Voxel-based morphometry, a brain mapping technique that measures gray matter volume, was used to model the relationship between weekly fish consumption at baseline and brain structure 10 years later. The data were then analyzed to determine if gray matter volume preservation associated with fish consumption reduced risk for Alzheimer's disease. The study controlled for age, gender, education, race, obesity, physical activity, and the presence or absence of apolipoprotein E4 (ApoE4), a gene that increases the risk of developing Alzheimer's.
Gray matter volume is crucial to brain health. When it remains higher, brain health is being maintained. Decreases in gray matter volume indicate that brain cells are shrinking.
The findings showed that consumption of baked or broiled fish on a weekly basis was positively associated with gray matter volumes in several areas of the brain. Greater hippocampal, posterior cingulate and orbital frontal cortex volumes in relation to fish consumption reduced the risk for five-year decline to MCI or Alzheimer's by almost five-fold.
"Consuming baked or broiled fish promotes stronger neurons in the brain's gray matter by making them larger and healthier," Dr. Raji said. "This simple lifestyle choice increases the brain's resistance to Alzheimer's disease and lowers risk for the disorder."
The results also demonstrated increased levels of cognition in people who ate baked or broiled fish.
"Working memory, which allows people to focus on tasks and commit information to short-term memory, is one of the most important cognitive domains," Dr. Raji said. "Working memory is destroyed by Alzheimer's disease. We found higher levels of working memory in people who ate baked or broiled fish on a weekly basis, even when accounting for other factors, such as education, age, gender and physical activity."
Eating fried fish, on the other hand, was not shown to increase brain volume or protect against cognitive decline.
**Source: Radiological Society of North America
Alzheimer's disease is an incurable, progressive brain disease that slowly destroys memory and cognitive skills. According to the National Institute on Aging, as many as 5.1 million Americans may have Alzheimer's disease. In MCI, memory loss is present but to a lesser extent than in Alzheimer's disease. People with MCI often go on to develop Alzheimer's disease.
For the study, 260 cognitively normal individuals were selected from the Cardiovascular Health Study. Information on fish consumption was gathered using the National Cancer Institute Food Frequency Questionnaire. There were 163 patients who consumed fish on a weekly basis, and the majority ate fish one to four times per week. Each patient underwent 3-D volumetric MRI of the brain. Voxel-based morphometry, a brain mapping technique that measures gray matter volume, was used to model the relationship between weekly fish consumption at baseline and brain structure 10 years later. The data were then analyzed to determine if gray matter volume preservation associated with fish consumption reduced risk for Alzheimer's disease. The study controlled for age, gender, education, race, obesity, physical activity, and the presence or absence of apolipoprotein E4 (ApoE4), a gene that increases the risk of developing Alzheimer's.
Gray matter volume is crucial to brain health. When it remains higher, brain health is being maintained. Decreases in gray matter volume indicate that brain cells are shrinking.
The findings showed that consumption of baked or broiled fish on a weekly basis was positively associated with gray matter volumes in several areas of the brain. Greater hippocampal, posterior cingulate and orbital frontal cortex volumes in relation to fish consumption reduced the risk for five-year decline to MCI or Alzheimer's by almost five-fold.
"Consuming baked or broiled fish promotes stronger neurons in the brain's gray matter by making them larger and healthier," Dr. Raji said. "This simple lifestyle choice increases the brain's resistance to Alzheimer's disease and lowers risk for the disorder."
The results also demonstrated increased levels of cognition in people who ate baked or broiled fish.
"Working memory, which allows people to focus on tasks and commit information to short-term memory, is one of the most important cognitive domains," Dr. Raji said. "Working memory is destroyed by Alzheimer's disease. We found higher levels of working memory in people who ate baked or broiled fish on a weekly basis, even when accounting for other factors, such as education, age, gender and physical activity."
Eating fried fish, on the other hand, was not shown to increase brain volume or protect against cognitive decline.
**Source: Radiological Society of North America
Ha muerto Winstone Zulu, la cara más conocida del sida en África
Un día Wistone Zulu se presentó en el programa 'Buenos días Zambia' que emitía la televisión nacional. Se sentó en un sillón del estudio y cuando las cámaras le enfocaron dijo que tenía el VIH. Era 1990 y él la primera persona en África que admitía públicamente su condición de seropositivo. Desde entonces y hasta el pasado mes de octubre, cuando falleció por causas relacionadas con el sida, fue puerta por puerta y congreso tras congreso defendiendo los derechos de los pacientes con VIH. Su activismo lo convirtió en la cara más conocida del sida en el continente africano.
Su lucha por mejorar las cosas para los demás transcurrió de forma paralela a su lucha personal. No le fue fácil aceptar que había contraído el virus. Se enteró cuando ya tenía todo preparado para salir de su Zambia natal para ir a estudiar a Rusia. Lo único que le faltaba era un análisis médico, requisito que le pedían para viajar. Se lo hizo confiado, sin saber que con la sangre que le estaban sacando, le estaban quitando también su sueño.
Cuando le dieron el diagnóstico se hundió. Pensó que iba morir, como dos de sus hermanos, que ya habían fallecido por tuberculosis -una complicación recurrente de la infección por VIH-. Pero pensar en ellos le dio la fuerza necesaria para dar un paso al frente. ¿Y si hubieran estado también infectados sin saberlo? Cayó en la cuenta de que mucha gente estaba pasando por lo mismo que él pero nadie hablaba de eso. "Sentí que no tenía nada de lo que avergonzarme. Ser seropositivo no es lo mismo que ser un criminal y sólo ellos ocultan lo que han hecho. Yo no era un criminal, así que no tenía por qué esconderme", reconoció luego, según recuerda la revista 'The Lancet', que le rinde tributo.
Así que se plantó en la televisión y, a partir de ahí, en todos los lugares en los que quisieron escucharle. Reclamaba un mayor acceso al tratamiento antirretroviral pero también al tratamiento para la tuberculosis. Combatía la homofobia y defendía el derecho de los seropositivos a ser padres, algo que él llevó a cabo (tuvo cuatro hijos sanos, gracias a que su mujer tomó la nevirapina durante el embarazo y no amamantó a los bebés). Y para aumentar la conciencia sobre esta enfermedad fundó la organización 'Positive and Living Squad' (PALS).
"Era un hombre brillante, educado e increíblemente valiente a la hora de hablar de su situación cuando nadie más lo hacía por aquel entonces", recuerda en la revista médica Peter Godfrey-Fausset, profesor de la Escuela de Medicina Tropical de Londres.
El acceso a los fármacos era un tema que le preocupaba mucho. "Tengo amigos, matrimonios, que ambos tienen el virus y que solamente pueden conseguir tratamiento para uno de ellos. Así que tienen que componérselas para ver cuál se toma la medicación. ¿Se quedarán sus hijos sin padre o sin madre? ¿Qué clase de elección es ésa?", contaba indignado en el libro '28 historias de sida en África', de Stephanie Nolen.
Pero durante la conferencia sobre el sida de Ginebra (1998), Winstone cambió de opinión respecto a su enfermedad. Conoció a un grupo de los llamados "disidentes del sida", que pregonaban que el VIH no existía y que había sido un invento de las farmacéuticas. El activista se dejó seducir por ellos y abandonó sus cargos en todas las organizaciones de sida de las que formaba parte. Y, lo que es peor, dejó de tomar los antirretrovirales. Estuvo así dos años, hasta que cayó muy enfermo y retomó su medicación, fue consciente de que había cometido un error y volvió a sus ideas anteriores.
"Fue un luchador incansable por los derechos y la dignidad de los seropositivos. Gracias a él hoy 400.000 zambianos reciben antirretrovirales gratis. Su ejemplo dio la vuelta al mundo". Con estas palabras le despidió el presidente de Zambia, Michael Sala. Winstone se despidió con su sonrisa, siempre dispuesta pese a las dificultades.
Su lucha por mejorar las cosas para los demás transcurrió de forma paralela a su lucha personal. No le fue fácil aceptar que había contraído el virus. Se enteró cuando ya tenía todo preparado para salir de su Zambia natal para ir a estudiar a Rusia. Lo único que le faltaba era un análisis médico, requisito que le pedían para viajar. Se lo hizo confiado, sin saber que con la sangre que le estaban sacando, le estaban quitando también su sueño.
Cuando le dieron el diagnóstico se hundió. Pensó que iba morir, como dos de sus hermanos, que ya habían fallecido por tuberculosis -una complicación recurrente de la infección por VIH-. Pero pensar en ellos le dio la fuerza necesaria para dar un paso al frente. ¿Y si hubieran estado también infectados sin saberlo? Cayó en la cuenta de que mucha gente estaba pasando por lo mismo que él pero nadie hablaba de eso. "Sentí que no tenía nada de lo que avergonzarme. Ser seropositivo no es lo mismo que ser un criminal y sólo ellos ocultan lo que han hecho. Yo no era un criminal, así que no tenía por qué esconderme", reconoció luego, según recuerda la revista 'The Lancet', que le rinde tributo.
Así que se plantó en la televisión y, a partir de ahí, en todos los lugares en los que quisieron escucharle. Reclamaba un mayor acceso al tratamiento antirretroviral pero también al tratamiento para la tuberculosis. Combatía la homofobia y defendía el derecho de los seropositivos a ser padres, algo que él llevó a cabo (tuvo cuatro hijos sanos, gracias a que su mujer tomó la nevirapina durante el embarazo y no amamantó a los bebés). Y para aumentar la conciencia sobre esta enfermedad fundó la organización 'Positive and Living Squad' (PALS).
"Era un hombre brillante, educado e increíblemente valiente a la hora de hablar de su situación cuando nadie más lo hacía por aquel entonces", recuerda en la revista médica Peter Godfrey-Fausset, profesor de la Escuela de Medicina Tropical de Londres.
El acceso a los fármacos era un tema que le preocupaba mucho. "Tengo amigos, matrimonios, que ambos tienen el virus y que solamente pueden conseguir tratamiento para uno de ellos. Así que tienen que componérselas para ver cuál se toma la medicación. ¿Se quedarán sus hijos sin padre o sin madre? ¿Qué clase de elección es ésa?", contaba indignado en el libro '28 historias de sida en África', de Stephanie Nolen.
Pero durante la conferencia sobre el sida de Ginebra (1998), Winstone cambió de opinión respecto a su enfermedad. Conoció a un grupo de los llamados "disidentes del sida", que pregonaban que el VIH no existía y que había sido un invento de las farmacéuticas. El activista se dejó seducir por ellos y abandonó sus cargos en todas las organizaciones de sida de las que formaba parte. Y, lo que es peor, dejó de tomar los antirretrovirales. Estuvo así dos años, hasta que cayó muy enfermo y retomó su medicación, fue consciente de que había cometido un error y volvió a sus ideas anteriores.
"Fue un luchador incansable por los derechos y la dignidad de los seropositivos. Gracias a él hoy 400.000 zambianos reciben antirretrovirales gratis. Su ejemplo dio la vuelta al mundo". Con estas palabras le despidió el presidente de Zambia, Michael Sala. Winstone se despidió con su sonrisa, siempre dispuesta pese a las dificultades.
**Publicado en "EL MUNDO"
Caltech biologists deliver neutralizing antibodies that protect against HIV infection in mice
Over the past year, researchers at the California Institute of Technology (Caltech), and around the world, have been studying a group of potent antibodies that have the ability to neutralize HIV in the lab; their hope is that they may learn how to create a vaccine that makes antibodies with similar properties. Now, biologists at Caltech led by Nobel Laureate David Baltimore, president emeritus and Robert Andrews Millikan Professor of Biology, have taken one step closer to that goal: they have developed a way to deliver these antibodies to mice and, in so doing, have effectively protected them from HIV infection. This new approach to HIV prevention -- called Vectored ImmunoProphylaxis, or VIP -- is outlined in the November 30 advance online publication of the journal Nature.
Traditional efforts to develop a vaccine against HIV have been centered on designing substances that provoke an effective immune response -- either in the form of antibodies to block infection or T cells that attack infected cells. With VIP, protective antibodies are being provided up front.
"VIP has a similar effect to a vaccine, but without ever calling on the immune system to do any of the work," says Alejandro Balazs, lead author of the study and a postdoctoral scholar in Baltimore's lab. "Normally, you put an antigen or killed bacteria or something into the body, and the immune system figures out how to make an antibody against it. We've taken that whole part out of the equation."
Because mice are not sensitive to HIV, the researchers used specialized mice carrying human immune cells that are able to grow HIV. They utilized an adeno-associated virus (AAV) -- a small, harmless virus that has been useful in gene-therapy trials -- as a carrier to deliver genes that are able to specify antibody production. The AAV was injected into the leg muscle of mice, and the muscle cells then put broadly neutralizing antibodies into the animals' circulatory systems. After just a single AAV injection, the mice produced high concentrations of these antibodies for the rest of their lives, as shown by intermittent sampling of their blood. Remarkably, these antibodies protected the mice from infection when the researchers exposed them to HIV intravenously.
The team points out that the leap from mice to humans is large -- the fact that the approach works in mice does not necessarily mean it will be successful in humans. Still, the researchers believe that the large amounts of antibodies that the mice were able to produce -- coupled with the finding that a relatively small amount of antibody has proved protective in the mice -- may translate into human protection against HIV infection.
"We're not promising that we've actually solved the human problem," says Baltimore. "But the evidence for prevention in these mice is very clear."
The paper also notes that in the mouse model, VIP worked even in the face of increased exposure to HIV. To test the efficacy of the antibody, the researchers started with a virus dose of one nanogram, which was enough to infect the majority of the mice who received it. When they saw that the mice given VIP could withstand that dose, they continued to bump it up until they were challenging them with 125 nanograms of virus.
"We expected that at some dose, the antibodies would fail to protect the mice, but it never did -- even when we gave mice 100 times more HIV than would be needed to infect 7 out of 8 mice," says Balazs. "All of the exposures in this work were significantly larger than a human being would be likely to encounter."
He points out that this outcome likely had more to do with the properties of the antibody that was tested than the method, but adds that VIP is what enabled the large amount of this powerful antibody to circulate through the mice and fight the virus. Furthermore, VIP is a platform technique, meaning that as more potent neutralizing antibodies are isolated or developed for HIV or other infectious organisms, they can also be delivered using this method.
"If humans are like mice, then we have devised a way to protect against the transmission of HIV from person to person," says Baltimore. "But that is a huge if, and so the next step is to try to find out whether humans behave like mice."
He says the team is currently in the process of developing a plan to test their method in human clinical trials. The initial tests will ask whether the AAV vector can program the muscle of humans to make levels of antibody that would be expected to be protective against HIV.
"In typical vaccine studies, those inoculated usually mount an immune response -- you just don't know if it's going to work to fight the virus," explains Balazs. "In this case, because we already know that the antibodies work, my opinion is that if we can induce production of sufficient antibody in people, then the odds that VIP will be successful are actually pretty high."
Traditional efforts to develop a vaccine against HIV have been centered on designing substances that provoke an effective immune response -- either in the form of antibodies to block infection or T cells that attack infected cells. With VIP, protective antibodies are being provided up front.
"VIP has a similar effect to a vaccine, but without ever calling on the immune system to do any of the work," says Alejandro Balazs, lead author of the study and a postdoctoral scholar in Baltimore's lab. "Normally, you put an antigen or killed bacteria or something into the body, and the immune system figures out how to make an antibody against it. We've taken that whole part out of the equation."
Because mice are not sensitive to HIV, the researchers used specialized mice carrying human immune cells that are able to grow HIV. They utilized an adeno-associated virus (AAV) -- a small, harmless virus that has been useful in gene-therapy trials -- as a carrier to deliver genes that are able to specify antibody production. The AAV was injected into the leg muscle of mice, and the muscle cells then put broadly neutralizing antibodies into the animals' circulatory systems. After just a single AAV injection, the mice produced high concentrations of these antibodies for the rest of their lives, as shown by intermittent sampling of their blood. Remarkably, these antibodies protected the mice from infection when the researchers exposed them to HIV intravenously.
The team points out that the leap from mice to humans is large -- the fact that the approach works in mice does not necessarily mean it will be successful in humans. Still, the researchers believe that the large amounts of antibodies that the mice were able to produce -- coupled with the finding that a relatively small amount of antibody has proved protective in the mice -- may translate into human protection against HIV infection.
"We're not promising that we've actually solved the human problem," says Baltimore. "But the evidence for prevention in these mice is very clear."
The paper also notes that in the mouse model, VIP worked even in the face of increased exposure to HIV. To test the efficacy of the antibody, the researchers started with a virus dose of one nanogram, which was enough to infect the majority of the mice who received it. When they saw that the mice given VIP could withstand that dose, they continued to bump it up until they were challenging them with 125 nanograms of virus.
"We expected that at some dose, the antibodies would fail to protect the mice, but it never did -- even when we gave mice 100 times more HIV than would be needed to infect 7 out of 8 mice," says Balazs. "All of the exposures in this work were significantly larger than a human being would be likely to encounter."
He points out that this outcome likely had more to do with the properties of the antibody that was tested than the method, but adds that VIP is what enabled the large amount of this powerful antibody to circulate through the mice and fight the virus. Furthermore, VIP is a platform technique, meaning that as more potent neutralizing antibodies are isolated or developed for HIV or other infectious organisms, they can also be delivered using this method.
"If humans are like mice, then we have devised a way to protect against the transmission of HIV from person to person," says Baltimore. "But that is a huge if, and so the next step is to try to find out whether humans behave like mice."
He says the team is currently in the process of developing a plan to test their method in human clinical trials. The initial tests will ask whether the AAV vector can program the muscle of humans to make levels of antibody that would be expected to be protective against HIV.
"In typical vaccine studies, those inoculated usually mount an immune response -- you just don't know if it's going to work to fight the virus," explains Balazs. "In this case, because we already know that the antibodies work, my opinion is that if we can induce production of sufficient antibody in people, then the odds that VIP will be successful are actually pretty high."
**Source: California Institute of Technology
La cerveza sin alcohol mejora la capacidad antioxidante de la leche materna según un estudio
El consumo moderado de cerveza sin alcohol puede optimizar la capacidad antioxidante de la leche materna, según sostiene el estudio "Efecto de la cerveza sin alcohol sobre la leche materna", que ha presentado este martes en el Colegio de Médicos de Almería la investigadora de la Facultad de Medicina de la Universidad de Valencia Victoria Valls, coautora del mismo. La investigación ha estudiado a 80 madres lactantes, de las que la mitad seguían una dieta habitual, mientras que a la otra mitad se les suplementó su dieta con dos cervezas sin alcohol al día durante 30 jornadas, según ha informado el Centro de Información Cerveza y Salud.
"Hemos determinado la capacidad antioxidante de la leche materna en tres momentos diferentes de la lactancia en función de su estado madurativo (al inicio o leche calostral, a los 15 días o leche transacional y al mes del inicio de la lactancia, cuando la leche se denomina madura)", ha detallado Valls. En concreto, esta investigadora sostiene que han observado una "disminución de la actividad antioxidante a medida que la leche humana va madurando", si bien "las madres lactantes que habían suplementado su dieta con cerveza sin alcohol manifestaron un descenso menor y más lento".
"De hecho -ha agregado- hemos comprobado que enriquecer la dieta de las madres lactantes con cerveza sin alcohol aumenta hasta un 30 por ciento la capacidad antioxidante de la leche materna". Asimismo, la investigación ha concluido que las madres que habían seguido la dieta suplementada con cerveza sin alcohol presentaban un menor daño en la oxidación celular, así como un aumento antioxidante, tanto en su sangre, como en su orina.
*"EUROPA PRESS"
"Hemos determinado la capacidad antioxidante de la leche materna en tres momentos diferentes de la lactancia en función de su estado madurativo (al inicio o leche calostral, a los 15 días o leche transacional y al mes del inicio de la lactancia, cuando la leche se denomina madura)", ha detallado Valls. En concreto, esta investigadora sostiene que han observado una "disminución de la actividad antioxidante a medida que la leche humana va madurando", si bien "las madres lactantes que habían suplementado su dieta con cerveza sin alcohol manifestaron un descenso menor y más lento".
"De hecho -ha agregado- hemos comprobado que enriquecer la dieta de las madres lactantes con cerveza sin alcohol aumenta hasta un 30 por ciento la capacidad antioxidante de la leche materna". Asimismo, la investigación ha concluido que las madres que habían seguido la dieta suplementada con cerveza sin alcohol presentaban un menor daño en la oxidación celular, así como un aumento antioxidante, tanto en su sangre, como en su orina.
*"EUROPA PRESS"
Genetic sequencing could help match patients with biomarker-driven cancer trials, treatments
As cancer researchers continue to identify genetic mutations driving different cancer subtypes, they are also creating a catalog of possible targets for new treatments. The University of Michigan Comprehensive Cancer Center and Michigan Center for Translational Pathology (MCTP) recently completed a pilot study aimed at solving the practical challenges involved in quickly and systematically sequencing genetic material from patients with advanced or treatment-resistant cancer in order to match them with existing clinical trials based on the biomarkers identified.
"We're talking about more than just examining a few genes where mutations are known to occur, or even about a hundred genes," says co-lead investigator Dan Robinson, Ph.D., a post-doctoral fellow at MCTP. "We're talking about the ability to sequence more than 20,000 genes and look not just for individual genetic mutations, but at combinations of mutations."
The exploratory study, known as the Michigan Oncology Sequencing Project (MI-ONCOSEQ), found that identifying a patient's "mutational landscape" provides a promising approach for identifying which trials may best help a patient, the researchers say. Their findings were recently published in Science Translational Medicine.
"High-throughput sequencing harnesses the latest technological advances to process millions of pieces of genetic information, allowing us to map a cancer's genetic aberrations," says co-lead investigator Sameek Roychowdhury, M.D., Ph.D., a clinical lecturer in hematology and oncology at the U-M Medical School. "Using this technique to identify biomarker-driven treatment options really opens the door for personalized oncology, but it also presents a number of logistical challenges, chief among them making the results available cost-effectively and in a clinically relevant timeframe."
"A decade or two ago, this type of sequencing would have cost many millions or even billions of dollars, but the technology is advancing so rapidly, we're now talking in terms of thousands -- which makes widespread use a real possibility," he adds.
Cancer can arise from a variety of genetic alterations including rearrangements, additions, deletions and substitutions within the genetic code.
"Different sequencing processes are required to find different types of alterations," Roychowdhury says. "But to be cost-effective, there must be a balancing act between a broad analysis and a deep analysis."
The study began by testing the researchers' sequencing strategy on prostate cancer tumors that had been grown in mice. Later, two patients were enrolled in a clinical pilot: one with colorectal cancer and one with melanoma. Potential clinical trials were identified for both patients.
However, the researchers caution, not all patients will match an existing study. Some patients with a given mutation may be excluded because they have, for example, prostate cancer, but a trial is only enrolling breast cancer patients. The researchers believe that this approach also provides an opportunity to approach clinical trials in a new way, moving from a tissue-specific focus toward genetic aberrations shared across cancer types.
Still, enrolling in a trial does not guarantee a patient will benefit from the treatment, the researchers caution.
Hurdles to widespread implementation include the need for a multidisciplinary Sequencing Tumor Board to interpret the complex sequencing results, management of the necessary computational resources, and a process for dealing with incidental genetic findings revealed by the sequencing -- such as a risk for hemochromatosis, a genetic disorder that causes the body to absorb too much iron.
Achieving a four-week turnaround time for results is important because that's how long patients are usually required to wait for unsuccessful treatments to leave their systems before starting a clinical trial.
"Once some of the practical and technological hurdles are cleared, we envision an array of mutation and pathway-based trials for available targeted therapies, with eligibility based on molecular assessment," says senior investigator Arul Chinnaiyan, M.D., Ph.D., director of MCTP, Howard Hughes Medical Institute Investigator, and S.P. Hicks Professor of Pathology at the U-M Medical School. "Moreover, if patients are treated with matching targeted therapies and develop secondary resistance, it could also help reveal the mechanisms of resistance and inform future trials for combination therapies."
Chinnaiyan says the work was made possible only by collaboration and teamwork. U-M physicians Moshe Talpaz, M.D., Stephen Gruber, M.D., Ph.D., and Kenneth Pienta, M.D. played key roles in the clinical implementation of this exploratory protocol, he notes.
Researchers hope this type of sequencing will become more widely available over the next 5 to 10 years. Cancer patients are encouraged to speak to their doctors about clinical trial opportunities.
**Source: University of Michigan Health System
"We're talking about more than just examining a few genes where mutations are known to occur, or even about a hundred genes," says co-lead investigator Dan Robinson, Ph.D., a post-doctoral fellow at MCTP. "We're talking about the ability to sequence more than 20,000 genes and look not just for individual genetic mutations, but at combinations of mutations."
The exploratory study, known as the Michigan Oncology Sequencing Project (MI-ONCOSEQ), found that identifying a patient's "mutational landscape" provides a promising approach for identifying which trials may best help a patient, the researchers say. Their findings were recently published in Science Translational Medicine.
"High-throughput sequencing harnesses the latest technological advances to process millions of pieces of genetic information, allowing us to map a cancer's genetic aberrations," says co-lead investigator Sameek Roychowdhury, M.D., Ph.D., a clinical lecturer in hematology and oncology at the U-M Medical School. "Using this technique to identify biomarker-driven treatment options really opens the door for personalized oncology, but it also presents a number of logistical challenges, chief among them making the results available cost-effectively and in a clinically relevant timeframe."
"A decade or two ago, this type of sequencing would have cost many millions or even billions of dollars, but the technology is advancing so rapidly, we're now talking in terms of thousands -- which makes widespread use a real possibility," he adds.
Cancer can arise from a variety of genetic alterations including rearrangements, additions, deletions and substitutions within the genetic code.
"Different sequencing processes are required to find different types of alterations," Roychowdhury says. "But to be cost-effective, there must be a balancing act between a broad analysis and a deep analysis."
The study began by testing the researchers' sequencing strategy on prostate cancer tumors that had been grown in mice. Later, two patients were enrolled in a clinical pilot: one with colorectal cancer and one with melanoma. Potential clinical trials were identified for both patients.
However, the researchers caution, not all patients will match an existing study. Some patients with a given mutation may be excluded because they have, for example, prostate cancer, but a trial is only enrolling breast cancer patients. The researchers believe that this approach also provides an opportunity to approach clinical trials in a new way, moving from a tissue-specific focus toward genetic aberrations shared across cancer types.
Still, enrolling in a trial does not guarantee a patient will benefit from the treatment, the researchers caution.
Hurdles to widespread implementation include the need for a multidisciplinary Sequencing Tumor Board to interpret the complex sequencing results, management of the necessary computational resources, and a process for dealing with incidental genetic findings revealed by the sequencing -- such as a risk for hemochromatosis, a genetic disorder that causes the body to absorb too much iron.
Achieving a four-week turnaround time for results is important because that's how long patients are usually required to wait for unsuccessful treatments to leave their systems before starting a clinical trial.
"Once some of the practical and technological hurdles are cleared, we envision an array of mutation and pathway-based trials for available targeted therapies, with eligibility based on molecular assessment," says senior investigator Arul Chinnaiyan, M.D., Ph.D., director of MCTP, Howard Hughes Medical Institute Investigator, and S.P. Hicks Professor of Pathology at the U-M Medical School. "Moreover, if patients are treated with matching targeted therapies and develop secondary resistance, it could also help reveal the mechanisms of resistance and inform future trials for combination therapies."
Chinnaiyan says the work was made possible only by collaboration and teamwork. U-M physicians Moshe Talpaz, M.D., Stephen Gruber, M.D., Ph.D., and Kenneth Pienta, M.D. played key roles in the clinical implementation of this exploratory protocol, he notes.
Researchers hope this type of sequencing will become more widely available over the next 5 to 10 years. Cancer patients are encouraged to speak to their doctors about clinical trial opportunities.
**Source: University of Michigan Health System
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