Una nueva vía para tratar la enfermedad de Huntington. Esto es lo que ha conseguido un equipo de investigadores de
la Universidad Emory en Atlanta (EE. UU.) y del Instituto de Genética y
Biología del Desarrollo de la Academia China de Ciencias (China), tras
lograr 'interrumpir' la mutación en el gen de la huntingtina mediante el uso de la técnica de edición genética ‘CRISPR/Cas9’, conocida
popularmente como el 'corta-pega' genético,
que permite borrar, añadir o cambiar genes a voluntad. El
descubrimiento, que ha sido probado con éxito en ratones, ha sido
publicado en la revista Journal of Clinical Investigation.
Los científicos han logrado corregir esta mutación, eliminar los agregados y revertir tanto la enfermedad como los síntomas motores.
¿Servirá esta técnica para humanos? Por el momento, ha funcionado en
ratones y abre una vía de esperanza para tratar estas y otras
enfermedades neurodegenerativas hereditarias como la esclerosis lateral
amiotrófica, la enfermedad de Parkinson, la ataxia de Friedreich o la enfermedad de Alzheimer.
Para su experimento, los investigadores emplearon un modelo animal -ratones- al que manipularon genéticamente para contar con el gen mutante de la huntingtina que
provoca la enfermedad en los seres humanos. Así, cuando los roedores
habían cumplido los 9 meses de edad, la proteína formó agregados en el cerebro y comenzaron a mostrar los problemas la proteína formó agregados en el cerebro y
comenzaron a mostrar los problemas motores característicos de la
enfermedad. En ese momento, inyectaron un virus adeno-asociado –parecido
al de los resfriados– con la secuencia CRISPR/Cas9 con el ARN guía para
el gen mutado de la huntingtina en el cuerpo estriado del cerebro de
los ratones con la intención de recortar parte de este gen que produce los agregados de proteínas tóxicas en el cerebro.
Los resultados fueron asombrosamente rápidos. En apenas 3 semanas, el tratamiento había conseguido reducir dramáticamente los agregados de la proteína defectuosa en dicha zona cerebral -casi habían desaparecido- y los ratones mejoraron increíblemente su control motor y su equilibrio.
Concretamente, en comparación con los ratones de control de Huntington,
los ratones inyectados con CRISPR / Cas9 mostraron mejoras
significativas en las pruebas de control motor, equilibrio y fuerza de
agarre, aunque no estaban al nivel de los ratones del grupo de control.
Sobre las
preocupaciones de seguridad genética, los investigadores mostraron que
las mutaciones de cambio activadas por CRISPR / Cas9 ocurrieron
predominantemente dentro del gen huntingtina y no en otros genes
potenciales. Sin embargo, los efectos a largo plazo y la seguridad de utilizar esta técnica en el cerebro de los humanos para expresar CRISPR / Cas9 tendrán que ser rigurosamente probados antes de aplicar este enfoque a los pacientes.
Referencia: Su Yang et al,
CRISPR/Cas9-mediated gene editing ameliorates neurotoxicity in mouse
model of Huntington?s disease, Journal of Clinical Investigation (2017).
DOI: 10.1172/JCI92087
Cell Transport ‘Traffic Jam’ Caused by Mutated Protein, Researchers Discover
Jun 08, 2017 02:56 pm | Alice Melão
A mutated form of the huntingtin (mHTT) protein has been acknowledged as the cause of Huntington’s disease, but researchers have not been fully clear about how it disrupts the function of brain cells. A study, “Mutant Huntingtin Disrupts the Nuclear Pore Complex,” that was published in the scientific journal Neuron provides new knowledge that can help […]
The postCell Transport ‘Traffic Jam’ Caused by Mutated Protein, Researchers Discoverappeared first onHuntington's Disease News.
Voyager Selects Gene Therapy Candidate for Huntington’s Clinical Trials
Jun 06, 2017 01:49 pm | Magdalena Kegel
Voyager Therapeutics has a new candidate for the treatment of Huntington’s disease. The selected gene therapy is called VY-HTT01 and aims to prevent the production of protein from the mutant huntingtin gene (HTT). The compound is now undergoing preclinical studies of drug characteristics and toxicology as the company plans to file an investigational new drug (IND) application […]
The postVoyager Selects Gene Therapy Candidate for Huntington’s Clinical Trialsappeared first onHuntington's Disease News.
Les cuento hace unas semanas conoci a Benjamin Muñoz y me beco para tomar un curso donde aprendi sobre una ciencia que utizanan en China para sanar a personas con todo tipo de enfermedades y sin medicamentos. Esta ciencia esta avalada por conocimiento ancestrales y hay registros cientificos, protocolos de investigación. Benjamín nuestro maestro es un caso de exito.
ZhiNeng QiGong es toda una cultura, cuya práctica se realiza con una actitud científica, promoviendo los cambios que buscamos obtener a través de toda una forma de vida que implica una serie de ejercicios físicos y mentales, así como los hábitos físicos, emocionales y mentales más evolucionados que puede cultivar el ser humano.
Es un trabajo de enorme mérito, capaz de transformarnos en nuestra mejor versión y, como consecuencia, cambiar lo que nos rodea. ZhiNeng QiGong puede ser practicado por todo tipo de personas. No está relacionado con corrientes políticas ni religiosas, no es un deporte ni un arte marcial.
Benjamín nos esta considenando para 2 Becas para nuestra comunidad en cada curso que de para nuestra comunidad Hntington. EH EH EH EH
Tenemos becas para nuestra comunidad Huntington, el 24 y 25 de junio, es para un paciente y un acompañante, LO UNICO QUE PEDIMOS A CAMBIO ES QUE LO UTILICES; TODOS LOS DIAS PARA PODER MEDIR MEJORAS.
Quién dice yo?.
Comunícate con Benjamín Muñoz Maestro de Zhinen QiGong
+52 1 55 5412 9940
What if a blood test could provide information about the status
and course of HD? This is the premise of seeking HD biomarkers; they may
someday help guide treatment decisions and predict how symptoms will
change. A team of researchers spanning multiple countries recently
analyzed blood, brain images, and clinical exams from the TRACK-HD
study. They found that blood levels of a protein called neurofilament
light chain corresponded with the severity of HD, making it a potential biomarker.
The search for HD biomarkers
With enduring community support of cutting-edge science, there is
great potential for the development of novel therapies to treat
Huntington’s disease. Alongside basic and clinical studies to identify
the source of symptoms and investigate new drugs, it’s important to seek
out accurate and efficient ways to track the progression of HD. As more
resources become available for treating and managing HD symptoms, it
would be helpful for doctors and patients to have a sense of whether a
person’s symptoms are expected to worsen slowly or quickly. We also need
accurate ways to determine whether an experimental drug has improved
brain health. Unlike previous biomarkers for HD, this new finding can be done using a simple blood sample.
There are established ways to address these questions: we can assess
unusual movements, analyze changes in mood and thinking, and take images
of the brain areas involved in HD. But these methods can be
time-consuming and draining for patients and doctors, and might be
uninformative for a person at risk who has not yet experienced symptoms.
For these reasons, the HD community is in search of good biomarkers,
tests that can be easily measured to predict disease development and
response to treatment. Today, we’re excited to report that researchers
in the UK have identified a substance in the blood that shows promise as
a biomarker for HD.
What is a biomarker, exactly?
We usually define a biomarker
as a test that can predict disease onset, progression, or success of
treatment. What does this actually mean? Well, with an excellent biomarker,
a simple test in a routine medical check-up can generate enough
information to guide decisions about current and future care. This has
not yet been possible with Huntington’s disease, nor with most
neurological disorders. The brain is a complex organ, and treatments are
limited compared to cancer, for example, or heart disease.
In fact, let’s take the example of heart disease to illustrate more clearly the concept of a biomarker. In the case of heart health, a simple and universal example of a biomarker
is blood pressure. Measuring blood pressure is easy, non-invasive, and
inexpensive. More importantly, a century of research has determined
definitively that blood pressure is a very good indication of risk for
heart disease. Increasing blood pressure readings over time might
warrant a change in diet or prescription of a medication, to decrease
the danger of future heart problems. If the interventions cause blood
pressure to decrease, the doctor and patient can be reasonably sure that
the risk of heart disease is now lower. These decisions and conclusions
can be made without ever directly testing the heart, and while the
patient is still physically feeling fine.
The ideal biomarker
for HD would serve a similar function. Although a genetic test can
determine whether a person has the HD mutation, it cannot predict the
short-term risk of developing symptoms, or determine the likely amount
of present damage to the brain. We also lack any basic chemical tests to
understand whether a new treatment is delaying symptoms or slowing
damage; instead patients must undergo frequent and lengthy testing. A
person at risk of developing HD may experience no symptoms for many
years, but imagine if a simple yearly test could give an indication of
brain health, the way blood pressure does for the heart. These are the
goals of seeking HD biomarkers.
Identifying potential biomarkers for HD
One way to search for HD biomarkers in humans is to measure levels of
many substances in the blood, then compare these levels with the
severity of symptoms or images of damage to the brain. Combining this
data from a large group of people can determine which substances should
be interpreted as a sign of health or damage. When something in the
blood increases (or decreases) steadily as neurological damage and
symptoms worsen, researchers start to pay attention - it could be a
potential biomarker.
For brain disorders, the search has been elusive. This is because it’s
rare for the contents of brain cells to end up in the bloodstream, and
because there’s huge variation in levels of blood substances among
individuals.
Nevertheless, a recent study, headed by Dr. Edward Wild at University
College London, has identified a protein in the blood that appears to
have this property: it increases in proportion to other signs of HD. To
identify this protein, the team analyzed data collected as part of
TRACK-HD, a three-year study of HD mutation carriers and their
unaffected partners or siblings. The clinicians were not testing a drug,
but making careful observations of participants over time to understand
more about the way HD develops. The 298 people who completed the trial
had repeated brain imaging, clinical exams to measure movement and
thinking, and gave blood samples. Their participation has fueled several
years of research, including this most recent biomarkers study.
Neurofilament light chain
The protein at the center of this story is called neurofilament light
chain, or NfL. It’s an important structural component of nerve cells,
supporting their shape, like the ribs of an umbrella. Previous research
in HD and other neurological disorders has shown that when a brain cell
dies, the umbrella collapses, releasing NfL protein that can end up in
the blood stream. This led Wild and his team to hypothesize that
increasing damage to the brain areas affected by HD would cause higher
levels of NfL to accumulate in the blood. The researchers decided to
investigate NfL more closely, using the blood samples, images, and exam
results from TRACK-HD participants.
“Imagine if a simple test could give as good an indication of HD brain health as blood pressure does for the heart
”
The participants were divided into groups based on the status of
their HD, determined by exams at the beginning of the study. There was a
“control” group made up of siblings or partners who did not have the
mutation. Then there were four groups of gene carriers: (1) those
predicted to develop HD symptoms in a decade or more, (2) those
predicted to develop symptoms in a few years, (3) those with early
symptoms, and (4) those with more advanced symptoms.
The more “advanced” disease group a person was in, the higher their
NfL levels, and NfL increased over time in people with the HD gene.
Importantly, the highest levels of NfL corresponded with more damage to
the brain and poorer scores on movement and reasoning tests. This means
that NfL levels were a good indicator of brain health and HD
progression. If a person had a high level of NfL at the beginning of the
study but no symptoms, they often began to develop symptoms during the
study. So not only were NfL levels associated with severity, they could
predict whether a person might become ill soon. What’s more, the level
of NfL in the blood reflected the amount found in the CSF,
the fluid bathing the brain. This suggests that a blood test might be
able to provide consistent information about the brain, in place of an
invasive spinal tap.
NfL: potential future as a biomarker
For all of these reasons, the authors propose that NfL could be used as a blood biomarker
that reflects current health of the brain in HD. This is a
well-designed experiment with robust data, making for exciting news. But
as with all studies, it’s important to discuss the limitations of this
work.
First and foremost, analyzing data from a big group of participants
is an excellent way to find general trends, but the interpretation won’t
extend to every individual. Just as high blood pressure indicates risk
of heart disease rather than setting the date of a heart attack, a
person’s NfL level cannot make an exact prediction about HD symptoms or
brain health. The levels are simply too variable between individuals,
and there’s not enough data yet to apply these findings to any routine
practice, such as a simple test in a doctor’s office.
However, measuring NfL levels could be an added way to assess disease
progression in HD clinical studies. It will be particularly interesting
to see whether current or future treatments can lower levels of NfL,
mirroring improvements in symptoms. One intriguing idea is that
scientists could revisit samples from past clinical trials to build a
larger picture of the relationship between NfL and HD progression, and
to determine whether experimental treatments lowered NfL, even if they
failed to improve symptoms.
Furthermore, before we can use blood NfL (or any other blood biomarker) as a proxy for damage to neurons
in HD, we have to be more certain that blood levels correspond with
levels in the brain. To address this issue, the team heading the recent
study has also launched a global initiative called HDClarity to ensure
that samples of CSF (obtained via a spinal tap) are collected and processed consistently in clinics all over the world.
If the observations about blood/CSF NfL levels and HD hold up under further scrutiny, we may have a useful biomarker on our hands. Notably, NfL is not specific for HD and has also been proposed as a marker to track the progression of other neurodegenerative
diseases, including Alzheimer’s and ALS. We hope it will be added to
the arsenal of resources that are helping us to monitor HD and to
develop new therapies. At the same time, researchers will continue to
seek out biomarkers that can help guide patients and families’ decisions
as treatments become available.
neurodegenerative A disease caused by progressive malfunctioning and death of brain cells (neurons)
biomarker a test of any kind - including blood
tests, thinking tests and brain scans - that can measure or predict the
progression of a disease like HD. Biomarkers may make clinical trials
of new drugs quicker and more reliable.
neuron Brain cells that store and transmit information
CSF A clear fluid produced by the brain, which surrounds and supports the brain and spinal cord.
Soy tan afortunada Gracias Dios que dentro de la gente que nos apoya esta el Talento de los Jovenes de Servicio Social.
Muchísimas Gracias Clara Terrones por acompañarme, a Naidel Ardila por haber organizado este hermoso David, evento donde se unen a nuestras filas los increibles elementos, de jovenes talentosos, que se, dejaran a México orgulloso de sus historias.
Gracias por creer en un paíss donde la tranformación individual es el eje de amor, bienestar social, sabiduria, inteligencia, riqueza, poder, liderazgo, gracias porque cada vez que me tocan los chicos de servicio social me impresionan que son más los que quieren hacer un México distino a los mediocres.
Los amo, bienvenidos al equipo EH EH EH EH, Gracias Santiago de Leon y José de la Garza...
Gracias Dios por permitir un equipo de jovenes mexicanos con talento tan generoso y con almas tan limpias. Gracias Clara Terrones por acompañarnos.
Fundación Verónica Ruiz
Enfermedades neurodegenerativas y Enfermedad de Huntington México
EH EH EH EH
Diagnóstico no es Destino
TE AMO MÉXICO
Fundación Verónica Ruiz AC junto con Centro Médico ABC te invitan a participar a nuestro Taller de información sobre enfermedad de Huntington n (EH) y nuestro protocolo onservacional para gente en riesgo de EH, no te pierdas ser parte de un proyecto internacional de bienestar, donde nos hacen unos chek ups los medicos todos los años y asi esto sirve para la investigación.
El costo de estas evaluaciones son $150,000 pero para nosoos son GRATIS para nosotros no tienen precio...
El miércoles 21 de Junio a las 8:00 pm.
Confirma tu asistencia 55 1247 3830
A mutated form of the huntingtin (mHTT) protein has been acknowledged as the cause of Huntington’s disease, but researchers have not been fully clear about how it disrupts the function of brain cells. A study, “Mutant Huntingtin Disrupts the Nuclear Pore Complex,” that was published in the scientific journal Neuron provides new knowledge that can help […]
Voyager Therapeutics has a new candidate for the treatment of Huntington’s disease. The selected gene therapy is called VY-HTT01 and aims to prevent the production of protein from the mutant huntingtin gene (HTT). The compound is now undergoing preclinical studies of drug characteristics and toxicology as the company plans to file an investigational new drug (IND) application […]
