Tag Archives: ALS

A paper titled “Case report of concurrent Fabry disease and amyotrophic lateral sclerosis supports a common pathway of pathogenesis” has been published in Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. This research was supported by JPND through the SOPHIA, STRENGTH and ALS-CarE projects.

 

A paper titled “The selective anatomical vulnerability of ALS: ‘disease-defining’ and ‘disease-defying’ brain regions” has been published in Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. The research group of Orla Hardiman received support from JPND through the SOPHIA project, which was selected for support in the 2011 biomarkers call.

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is a devastating progressive neurodegenerative disease that results in the death of motor neurons, the nerve cells that control muscles. Eventually, individuals with ALS will lose their ability to walk, move, swallow and breathe.

Until recently, the role of astrocytes, glial cells that normally support motor neurons, in motor neuron death has been a mystery, but new research sheds new light on molecular mechanisms responsible for motor neuron death in ALS. In a study published in Nature Medicine, researchers demonstrate the explicit loss of major histocompatibility complex I (MHCI) expression in the outer membrane of motor neurons in ALS, leading to motor neuron vulnerability to ALS astrocyte toxicity.

For each subtype of MHCI protein, there is a receptor that binds to it, much like a lock and key. If MCHI proteins are the keys, then killer inhibitory receptors (KIRs) are the locks. In their study, the researchers not only provide evidence of the protective effect of MHCI against astrocyte toxicity in ALS but also identify the killer inhibitory receptors (KIRs) associated with the specific subclass of MHCI (HLA-F) involved in human motor neurons.

According to the study, a dramatic loss of MHCI (HLA-F) from motor neurons is observed in the spinal cords of subjects affected by ALS. This finding is supported by evidence obtained in animal models and in vitro experiments using animal and human cells, which give insight on the protective nature of MHCI (HLA-F). Specifically, MHCI expression in the animal model was modulated using adeno-associated viral vector serotype 9 (AAV9), resulting in increased expression of MHCI and markedly extended survival.

The protective nature of MHCI (HLA-F) points to a potential translational target to delay the progression of ALS, since HLA-F expression may significantly impact disease progression in patients. In the in vitro experiments, human motor neurons expressing higher levels of HLA-F experienced reduced astrocyte toxicity. However, it remains to be seen whether or not this can be translated into a clinical trial and meaningful therapy for patients.

Source: Nationwide Children’s Hospital

The EU Joint Programme – Neurodegenerative Disease Research (JPND) has announced a rapid-action call inviting leading scientists in the field to bring forward novel approaches that will enhance the use of brain imaging for neurodegenerative disease research.

Imaging techniques such as MR, PET and EEG mapping have brought about a dramatic improvement in the understanding of neurodegenerative diseases such as Alzheimer’s disease. In recent years, access to cutting-edge imaging technologies and platforms has expanded, and advances have been made in the harmonisation of acquisition procedures across scanners and vendors. However, fully capitalising on the use of brain imaging technologies for neurodegeneration research will require the development of new methodologies and the ability to achieve image acquisition and analysis at scale and at the global level.

The aim of the call is to establish a limited number of transnational working groups to address the key challenges facing the use of new and innovative brain imaging techniques in neurodegenerative disease research. The working groups will be community-led and will establish ‘best practice’ guidelines and/or methodological frameworks to overcome these barriers. Each working group can bid up to €50,000 for the support of its activities, which are expected to run for a maximum of 9 months.

According to Professor Philippe Amouyel, Chair of the JPND Management Board:

“JPND recognises that state-of-the-art brain imaging techniques are a vital resource for neurodegenerative disease research. However, achieving scalability for these technologies poses new challenges. For this reason, we’ve launched a rapid-action call inviting international research teams to address the most urgent issues in harmonisation and alignment in neuroimaging. The establishment of effective new guidelines and methodological frameworks will represent a critical step toward the full exploitation of brain imaging in neurodegenerative disease research.”

The following neurodegenerative diseases are included in the call:

  • Alzheimer’s disease and other dementias
  • Parkinson’s disease and PD‐related disorders
  • Prion diseases
  • Motor neuron diseases
  • Huntington’s disease
  • Spinocerebellar ataxia (SCA)
  • Spinal muscular atrophy (SMA)

Proposals must be submitted by 23:59H C.E.T. on March 10, 2016.

For more information about the call, please click here.

 

Researchers are proposing a new way of understanding Amyotrophic Lateral Sclerosis (ALS), the devastating and incurable neurological disease. Their findings, published in the journal Neuron, could be a major milestone on the path to a treatment for both ALS and dementia.

By delving into a previously overlooked corner of ALS research, the team discovered a new way in which the disease kills nerve cells.

Many cases of ALS are sparked by a toxic build-up of certain proteins, which cause neurons in the brain and spinal cord to die. Over the last decade, mutations that cause ALS have been found in a growing number of genes that encode RNA-binding proteins. The protein they create commonly builds up inside the diseased brain and spinal cords in ALS patients. Until now, scientists haven’t thought this build-up was important to the disease process because it looked different from the types of protein accumulations — such as tau, amyloid and alpha synuclein — that are clearly toxic and always found in patients with Alzheimer’s, Parkinson’s and some forms of dementia.

The research team decided to take a closer look at these seemingly innocuous protein accumulations. They focused initially on the FUS protein, and discovered that these abnormal clumps could actually be a very important player in causing nerve cell damage and ALS. The research team found that mutations in FUS changed the property of FUS protein so that it tends to form very dense gels that do not easily re-melt and release their cargo appropriately. As a result, it’s unable to deliver the tools necessary for the neurons to stay healthy and do their job.

The next step is for researchers to find ways to prevent the solidification of the gel, or to reverse the hardening process, offering a key to a future drug to treat ALS and frontotemporal dementia — another disease in which the protein is active.

Source: University of Toronto

The EU Joint Programme – Neurodegenerative Disease Research (JPND) will shortly begin another action to support working groups on “Harmonisation and Alignment in Brain Imaging Methods for Neurodegeneration”.

The aim of the call is to establish a limited number of transnational, JPND-sponsored expert working groups to address issues of key relevance for the future use of brain imaging techniques in ND research. Each working group can bid up to €50,000 for support of its activities, which are expected to run for a maximum of 6 months.

This will be a 1-step call, anticipated to launch in early January 2016, with a likely submission deadline of March 2016. Further details will be provided on the call launch date in January 2016. However, any new ideas to tackle harmonisation and alignment in brain imaging will be welcome. For example, this may include:

  • Harmonisation of acquisition for current markers (acquisition and harmonisation of procedures, for example, for MR, FDG PET, and EEG signals)
  • Simplification of web access to image analysis environments (improving the secure access to innovative web-based image analysis environments for neurodegenerative diseases)
  • Innovative PET molecular markers (fostering the use of established and experimental PET methods)
  • Innovative ultra-high field (UHF) MR markers

Please Note:

  • Proposals are not limited to these topics, and may cover other topics within harmonisation and alignment of brain imaging methods.
  • All information regarding future JPND Call topics is subject to change.
  • Final call information will be published on the JPND website (www.jpnd.eu).

The diseases covered by JPND are:
– Alzheimer’s disease (AD) and other dementias
– Parkinson’s disease (PD) and PD‐related disorders
– Prion disease
– Motor neurone diseases (MND)
– Huntington’s Disease (HD)
– Spinocerebellar ataxia (SCA)
– Spinal muscular atrophy (SMA)

 

An international team of researchers has developed a method for fabricating nano-scale electronic scaffolds that can be injected via syringe. Once connected to electronic devices, the scaffolds can be used to monitor neural activity, stimulate tissues and even promote regenerations of neurons.

The study entitled “Syringe-injectable electronics” was recently published in the journal Nature.

Nanotechnology and revealed an innovative method to employ tiny electronic devices in the brain, or other parts of the body, as a potential therapy for a wide range of disorders, including neurodegenerative diseases like amyotrophic lateral sclerosis (ALS). The study was performed by researchers at the Harvard University in Cambridge, Massachusetts and the National Center for Nanoscience and Technology in China.

The team had previously shown that cardiac or nerve cells grown with embedded nano-scale electronic scaffolds could generate a so-called “cyborg” tissue. The electronic devices could then record the electrical signals generated by the tissues, and measure signal changes when cardio- or neuro-stimulating drugs were administered to the cells.

Minimally invasive targeted delivery of electronics into artificial or natural structures is however a challenge. “We were able to demonstrate that we could make this scaffold and culture cells within it, but we didn’t really have an idea how to insert that into pre-existing tissue,” explained the study’s senior author Dr. Charles Lieber in a news release. Now, Dr. Lieber and colleagues have developed a pioneering method where sub-micrometer-thick mesh electronics can be delivered to their target through injection via a syringe.

Though not the first attempts at implanting electronics into the brain — deep brain stimulation has been used to treat a variety of disorders for decades — the nano-fabricated scaffolds operate on a completely different scale.

“Existing techniques are crude relative to the way the brain is wired,” Lieber explained. “Whether it’s a silicon probe or flexible polymers…they cause inflammation in the tissue that requires periodically changing the position or the stimulation. But with our injectable electronics, it’s as if it’s not there at all. They are one million times more flexible than any state-of-the-art flexible electronics and have subcellular feature sizes. They’re what I call “neuro-philic” — they actually like to interact with neurons.

Source:  Science Daily

Scientists at Mayo Clinic, Jacksonville, Florida, USA have created a novel mouse that exhibits the symptoms and neurodegeneration associated with the most common genetic forms of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), both of which are caused by a mutation in the a gene called C9ORF72. The study was published in the journal Science.

ALS destroys nerves that control essential movements, including speaking, walking, breathing and swallowing. After Alzheimer’s disease, FTD is the most common form of early onset dementia. It is characterized by changes in personality, behavior and language due to loss of neurons in the brain’s frontal and temporal lobes. Patients with mutations in the chromosome 9 open reading frame 72 (C9ORF72) gene have all or some symptoms associated with both disorders.

“Our mouse model exhibits the pathologies and symptoms of ALS and FTD seen in patients with theC9ORF72 mutation,” said the study’s lead author, Leonard Petrucelli, Ph.D., chair and Ralph and Ruth Abrams Professor of the Department of Neuroscience at Mayo Clinic, and a senior author of the study. “These mice could greatly improve our understanding of ALS and FTD and hasten the development of effective treatments.”

To create the model, Ms. Jeannie Chew, a Mayo Graduate School student and member of Dr. Petrucelli’s team, injected the brains of newborn mice with a disease-causing version of the C9ORF72 gene. As the mice aged, they became hyperactive, anxious, and antisocial, in addition to having problems with movement that mirrored patient symptoms. The brains of the mice were smaller than normal and had fewer neurons in areas that controlled the affected behaviors. The scientists also found that the mouse brains had key hallmarks of the disorders, including toxic clusters of ribonucleic acids (RNA) and TDP-43, a protein that has long been known to go awry in the majority of ALS and FTD cases.

“Finding TDP-43 in these mice was unexpected” Dr. Petrucelli said. “We don’t yet know how foci and c9RAN proteins are linked to TDP-43 abnormalities, but with our new animal model, we now have a way to find out.” Dr. Petrucelli and his team think these results are an important step in the development of therapies for these forms of ALS and FTD and other neurodegenerative disorders.

Chew et al. “C9ORF72 Repeat Expansions in Mice Cause TDP-43 Pathology, Neuronal Loss and Behavioral Deficits,” Science, May 14, 2015. DOI: 10.1126/science.aaa9344

Using data from old clinical trials, two groups of researchers have found a better way to predict how amyotrophic lateral sclerosis (ALS) progresses in different patients. The winning algorithms—designed by non-ALS experts—outperformed the judgments of a group of ALS clinicians given the same data. The advances could make it easier to test whether new drugs can slow the fatal neurodegenerative disease.

The new work was inspired by the so-called ALS Prediction Prize, a joint effort by the ALS-focused nonprofit Prize4Life and Dialogue for Reverse Engineering Assessments and Methods (DREAM), a computational biology project whose sponsors include IBM and Columbia University. Announced in 2012, the $50,000 award was designed to bring in experts from outside the ALS field to tackle the notoriously unpredictable illness.