UC Davis Multidisciplinary ALS Clinic named center of excellence

Designation highlights centers offering highest level of evidence-based quality care, services.

By Phyllis Brown, UC Davis

The UC Davis Multidisciplinary ALS Clinic has been named an ALS Association Certified Treatment Center of Excellence, in acknowledgement of its meeting the highest levels of established national standards of care for the management of amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s disease.

“We feel very fortunate and thankful to have received this designation from the ALSA,” said Nanette Joyce, assistant professor of clinical physical medicine and rehabilitation and co-director of the Multidisciplinary ALS Clinic. “We have always believed that the ALSA and particularly the Sacramento Chapter are important members of our multidisciplinary ALS team. Their efforts, both in and out of clinic, help our patients in so many meaningful ways. To have received this recognition, that binds our efforts, is breathtaking.”

Clinic leadership and representatives of the ALS Association Greater Sacramento Chapter will gather to celebrate the accomplishment during an event at the Ellison Ambulatory Care Center at UC Davis on Tuesday, Dec. 16, at 2 p.m. The event will feature the presentation of a donation of $11,500 from the chapter.

ALS is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. Eventually, people with ALS lose the ability to initiate and control muscle movement, which often leads to total paralysis and death within two to five years of diagnosis. There currently is no cure for ALS. The disorder has become more familiar to many in recent months, because of the highly successful “ice bucket challenge” campaign.

Certified Treatment Centers of Excellence must meet rigorous eligibility criteria, including diversity of professional expertise in ALS; access to coordinated, multidisciplinary care; a strong, ongoing relationship with the local ALS Association chapter; and evidence of active participation in ALS research.

The designation highlights the expertise of centers offering the highest level of evidence-based, quality care and services. The UC Davis ALS Clinic is built on four interrelated tenets:

  • Correct diagnosis: ALS can appear differently in people, and there are other diseases that may initially appear similar to ALS.
  • Multidisciplinary team care: Bringing together a range of specialists to create comprehensive care plans designed to help the whole person.
  • Education: Educating patients, who in turn help educate physicians and therapists in training to recognize and understand the challenges of ALS.
  • Research: Through research we can learn better ways of living with and treating the disease while working to develop a cure.

“We are proud to be a partner with UC Davis on this important project,” said Shawn Joost, executive director of the ALS Association Greater Sacramento Chapter. “When patients are attending the clinic, we know they are receiving the highest level of evidence-based, multidisciplinary care in a kind and supportive environment, designed to promote their independence.”

“We look forward to our continuing relationship with the clinic in service to patients and in support of the important ALS research being conducted there,” she said.

Research has shown that multidisciplinary care, or the practice of having physicians and other health care professionals collaborate to provide the most comprehensive treatment plan for patients, helps people with ALS have better quality of life and actually prolongs life in most cases. UC Davis has a long history of providing such care.

“Through research, we strive to understand ALS so that we can learn better ways of treating the disease,” said Björn Oskarsson, professor in the Department of Neurology and co-director of the clinic. “We engage ALS in many ways. In the short term, we conduct studies to figure out why ALS occurs and what makes ALS progress the way it does, to find ways of helping people live better with ALS, and to treat the disease with promising experimental therapies. In the long term, we are working to develop stem cell treatments for ALS through the UC Davis Institute for Regenerative Cures.”

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UC will lead effort to create library of brain cell activity

NIH program will advance fight against ALS, other neurodegenerative diseases.

Leslie Thompson, UC Irvine

UC Irvine will receive $8 million from the National Institutes of Health to establish one of six national centers dedicated to creating a database of human cellular responses that will accelerate efforts to develop new therapies for many diseases.

Leslie M. Thompson, UCI professor of psychiatry & human behavior and neurobiology & behavior, will partner with researchers from Cedars-Sinai Medical Center’s Regenerative Medicine Institute, the Gladstone Institute of Neurological Disease, UC San Francisco, Johns Hopkins University and the Massachusetts Institute of Technology.

They will study brain cell activity in motor neuron disorders including ALS and build a detailed archive of these disease “signatures” that identifies cell targets for new drug treatments. ALS, or amyotrophic lateral sclerosis, also called Lou Gehrig’s disease, attacks motor neurons, cells that control the muscles.

Overall, the NIH is awarding $64 million to six research groups to establish centers that support the Library of Integrated Network-Based Cellular Signatures program. The UC Irvine-based center will be called NeuroLINCS.

The goal of the LINCS program is to utilize the latest cutting-edge technology and scientific methods to catalog and analyze cellular function and molecular activity in response to perturbing agents – such as drugs and genetic factors – that have specific effects on cells. LINCS researchers will measure the cells’ tiniest molecular and biochemical responses and use computer analyses to uncover common patterns – called signatures. LINCS data will be freely available to any scientist.

“Human brain cells are far less understood than other cells in the body,” said Thompson, who’s affiliated with the Sue & Bill Gross Stem Cell Research Center and UCI MIND. “The collective expertise of NeuroLINCS investigators provides a unique opportunity to increase our knowledge of what makes brain cells unique and what happens during neurodegenerative diseases – with a strong focus toward effective treatments. We feel this will have broad application to a number of human brain diseases.”

She and her colleagues will study the effects, or signatures, of perturbing agents on induced pluripotent stem cell-derived neurons and glial cells from “unaffected” cells and those exhibiting the pathology of motor neuron diseases.

At UC Irvine, Thompson will work closely with the UCI Genomics High-Throughput Facility to explore gene expression patterns in these brain cells, which is expected to yield novel insights into pathways and gene networks that guide the development of cell signatures.

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UCSF expands access for people with ALS

Santa Rosa satellite clinic, pilot telemedicine initiative offer new options to patients, families.

The ALS Treatment and Research Center, a clinical practice of the Department of Neurology at UC San Francisco and an ALS Association-certified Center of Excellence, is expanding its support for the community of people facing amyotrophic lateral sclerosis (ALS).

In partnership with The ALS Association Golden West Chapter, the center is expanding direct service through a new satellite clinic in Santa Rosa. In addition, the UCSF Department of Neurology is launching a pilot program in telemedicine technology that will eventually allow people with ALS throughout California to access the center’s services from their homes.

ALS, also known as Lou Gehrig’s disease, is a fatal neurodegenerative disease that attacks nerve cells in the spinal cord and brain. People with ALS progressively lose their ability to move, speak, swallow, and eventually their ability to breathe, while all five senses continue to function normally.

ALS can strike men or women of any age, though, for reasons that are not fully understood, military veterans are at twice the risk as the general population. The average life expectancy of a person with ALS is two to five years from diagnosis. There is no known cause and no cure. In the later stages of the disease, the annual costs for home care, coupled with the cost of necessary equipment, can exceed $200,000 per year.

There are only 34 Centers of Excellence certified by The ALS Association in the United States. Each employs multidisciplinary clinic teams of healthcare professionals from several fields— including neurology, nursing, nutrition, physical therapy, occupational therapy, speech therapy and social work — to provide the highest standard of care for people with ALS.

With key support from The ALS Association Golden West Chapter, UCSF began offering a satellite multidisciplinary clinic in Monterey in 2005, to better serve the southern Bay Area and Central Coast ALS community. A second satellite clinic, which will offer services at six-month intervals, has begun operations at 100 Brookwood Ave. in Santa Rosa, to help people with ALS in the northern Bay Area receive services closer to home. The first Santa Rosa clinic was held in March, and the next will be held Oct. 23 and 24.

“Multidisciplinary clinics such as ours at UCSF Medical Center improve the quality of life for people with ALS and prolong survival, but it can be very difficult for families to travel extended distances to come to these clinics,” said Catherine Lomen-Hoerth, M.D., Ph.D., medical director of the ALS Treatment and Research Center at UCSF. “This support from The ALS Association Golden West Chapter for our satellite clinics greatly increases access to care for people throughout the Bay Area living with ALS.”

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New therapeutic target ID’d for ALS

New approach also holds promise for developing treatment of frontotemporal degeneration.

A team of scientists led by researchers from the UC San Diego School of Medicine and Ludwig Institute for Cancer Research have identified a novel therapeutic approach for the most frequent genetic cause of ALS, a disorder of the regions of the brain and spinal cord that control voluntary muscle movement, and frontotemporal degeneration, the second most frequent dementia.

Published ahead of print in last week’s online edition of the journal PNAS, the study establishes using segments of genetic material called antisense oligonucleotides – ASOs – to block the buildup and selectively degrade the toxic RNA that contributes to the most common form of ALS, without affecting the normal RNA produced from the same gene.

The new approach may also have the potential to treat frontotemporal degeneration or frontotemporal dementia (FTD), a brain disorder characterized by changes in behavior and personality, language and motor skills that also causes degeneration of regions of the brain.

In 2011, scientists found that a specific gene known as C9orf72 is the most common genetic cause of ALS. It is a very specific type of mutation which, instead of changing the protein, involves a large expansion, or repeated sequence of a set of nucleotides – the basic component of RNA.

A normal C9orf72 gene contains fewer than 30 of the nucleotide repeat unit, GGGGCC. The mutant gene may contain hundreds of repeats of this unit, which generate a repeat containing RNA that the researchers show aggregate into foci.

“Remarkably, we found two distinct sets of RNA foci, one containing RNAs transcribed in the sense direction and the other containing anti-sense RNAs,” said first author Clotilde Lagier-Tourenne, M.D., Ph.D., UC San Diego Department of Neurosciences and Ludwig Institute for Cancer Research.

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UC awarded $21M in stem cell grants

Diseases targeted include prostate cancer, autism, ALS and AIDS/HIV.

Alysson Muotri, UC San DIego

Alysson Muotri, UC San DIego

The University of California and its affiliates received seven grants totaling more than $21 million in the latest round of funding from the state’s stem cell agency.

Prostate cancer, autism, ALS and AIDS/HIV are among the diseases targeted by the California Institute for Regenerative Medicine, whose governing board awarded a total of more than $40 million in funding for this round.

Overall, CIRM’s governing board has awarded more than $1.8 billion in stem cell grants, with half of the total going to the University of California or UC-affiliated institutions.

CIRM Early Translation Awards IV:

  • UC Irvine: $4.3 million: Magdalene Seiler
  • UCLA: $13 million: Donald Kohn, Gerald Lipshutz, Robert Reiter, Jerome Zack
  • UC San Diego: $1.8 million: Alysson Muotri
  • UCSF-affiliated J. David Gladstone Institutes: $2.3 million: Steven Finkbeiner

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Scientists ID compounds that target amyloid fibrils in Alzheimer’s

UCLA study is first to use “structural” approach in hunt for amyloid-inhibiting agents.

Compounds binding to amyloid fibrils

Compounds binding to amyloid fibrils

UCLA chemists and molecular biologists have for the first time used a “structure-based” approach to drug design to identify compounds with the potential to delay or treat Alzheimer’s disease, and possibly Parkinson’s, Lou Gehrig’s disease and other degenerative disorders.

All of these diseases are marked by harmful, elongated, rope-like structures known as amyloid fibrils, linked protein molecules that form in the brains of patients.

Structure-based drug design, in which the physical structure of a targeted protein is used to help identify compounds that will interact with it, has already been used to generate therapeutic agents for a number of infectious and metabolic diseases.

The UCLA researchers, led by David Eisenberg, director of the UCLA–Department of Energy Institute of Genomics and Proteomics and a Howard Hughes Medical Institute investigator, report the first application of this technique in the search for molecular compounds that bind to and inhibit the activity of the amyloid-beta protein responsible for forming dangerous plaques in the brain of patients with Alzheimer’s and other degenerative diseases.

In addition to Eisenberg, who is also a professor of chemistry, biochemistry and biological chemistry and a member of UCLA’s California NanoSystems Institute, the team included lead author Lin Jiang, a UCLA postdoctoral scholar in Eisenberg’s laboratory and Howard Hughes Medical Institute researcher, and other UCLA faculty.

The research was published July 16 in eLife, a new open-access science journal backed by the Howard Hughes Medical Institute, the Max Planck Society and the Wellcome Trust.

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Regulating single protein prompts fibroblasts to become neurons

Findings could have implications for developing new treatments for Parkinson’s, Alzheimer’s.

Confocal micrograph of a primary human fibroblast cell grown in culture stained blue for actin, a highly abundant protein that makes up the cytoskeleton of cells.Energy-producing mitochondria are shown in green.

Repression of a single protein in ordinary fibroblasts is sufficient to directly convert the cells – abundantly found in connective tissues – into functional neurons. The findings, which could have far-reaching implications for the development of new treatments for neurodegenerative diseases like Huntington’s, Parkinson’s and Alzheimer’s, will be published online in advance of the Jan. 17 issue of the journal Cell.

In recent years, scientists have dramatically advanced the ability to induce pluripotent stem cells to become almost any type of cell, a major step in many diverse therapeutic efforts. The new study focuses upon the surprising and singular role of PTB, an RNA-binding protein long known for its role in the regulation of alternative RNA splicing.

In in vitro experiments, scientists at the UC San Diego School of Medicine and Wuhan University in China describe the protein’s notable regulatory role in a feedback loop that also involves microRNA – a class of small molecules that modulate the expression of up to 60 percent of genes in humans. Approximately 800 miRNAs have been identified and characterized to various degrees.

One of these miRNAs, known as miR-124, specifically modulates levels of PTB during brain development. The researchers found that when diverse cell types were depleted of PTB, they became neuronal-like cells or even functional neurons – an unexpected effect. The protein, they determined, functions in a complicated loop that involves a group of transcription factors dubbed REST that silences the expression of neuronal genes in non-neuronal cells.

According to principal investigator Xiang-Dong Fu, Ph.D., professor of cellular and molecular medicine at UC San Diego, it’s not known which neuronal signal or signals turn on the loop, which in principle can happen at any point in the circle. But the ability to artificially manipulate PTB levels in cells, inducing them to become neurons, offers tantalizing possibilities for scientists seeking new treatments for an array of neurodegenerative diseases.

It is estimated that over a lifetime, 1 in 4 Americans will suffer from a neurodegenerative disease, from Alzheimer’s and Parkinson’s to multiple sclerosis and amyotrophic lateral sclerosis (Lou Gehrig’s disease).

“All of these diseases are currently incurable. Existing therapies focus on simply trying to preserve neurons or slow the rate of degeneration,” said Fu. “People are working with the idea of replacing lost neurons using embryonic stem cells, but there are a lot of challenges, including issues like the use of foreign DNA and the fact that it’s a very complex process with low efficiency.”

Fu explained that REST is expressed in cells everywhere except in neurons. PTB is itself a target of miR-124, but also acts as a break for this microRNA to attack other cellular targets that include REST, which is responsible for repressing miR-124.

In non-neuronal cells, REST keeps miR-124 down and PTB enforces this negative feedback loop, but during neural induction, miR-124 is induced, which diminishes PTB, and without PTB as a break, REST is dismantled, and without REST, additional miR-124 is produced. This loop therefore becomes a positive feed forward, which turns non-neuronal cells into neurons.

“If we learn how to manipulate PTB, which appears to be a kind of master regulator, we might eventually be able to avoid some of these problems by creating new neurons in patients using their own cells adjacent deteriorating neurons,” said Fu.

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Scientists block toxic protein that plays key role in ALS

Findings suggest therapeutic target for treating fatal disease.

Robert Farese Jr.

Scientists at the UC San Francisco-affiliated Gladstone Institutes and the Stanford University School of Medicine have discovered how modifying a gene halts the toxic buildup of a protein found in nerve cells. These findings point to a potential new tactic for treating a variety of neurodegenerative conditions, including amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s disease) — a fatal disease for which there is no cure.

The Gladstone and Stanford scientists began their experiments independently before realizing that combining their efforts could strengthen their results. Their discovery — which involved the work of both neuroscientists and geneticists — underscores the importance of collaborative and cross-disciplinary research when dealing with complex neurodegenerative diseases such as ALS.

ALS usually strikes between the ages of 40 and 75, ravaging the body’s motor neurons — nerve cells that control muscle movement. This causes muscle weakness, difficulty swallowing and breathing, paralysis and, ultimately, death — often just three to five years after diagnosis. At any given time, as many as 30,000 Americans are living with ALS — which afflicts physicist Stephen Hawking and which killed baseball legend Lou Gehrig.

In a paper published today (Oct. 29) online in Nature Genetics, researchers in the laboratories of Aaron D. Gitler, Ph.D., associate professor at Standord, and Gladstone senior investigators Robert V. Farese Jr., M.D. and Steve Finkbeiner, M.D., Ph.D., describe how shutting off a gene called Dbr1 in yeast cells and in neurons obtained from rats can protect both cell types from the toxic effects of TDP-43 — a protein that plays a key role in ALS.

“Mutations in the gene that produces TDP-43 can cause this protein to build up in cells,” said Farese, who is also a professor at UCSF. “Over time, TDP-43 accumulation inside motor neurons can reach toxic levels and bind to RNAs — small bits of genetic material that act as an intermediary between genes and proteins. One theory is that this binding interferes with the RNAs’ normal functions and impairs the overall health of cells. Eventually, the neurons degrade and die, contributing to the rapid progression of ALS symptoms.”

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Common RNA pathway found in ALS, dementia

Discovery reveals set of target genes that could lead to development of new drug treatments.

Principal investigator Gene Yeo, UC San Diego

Two proteins previously found to contribute to ALS, also known as Lou Gehrig’s disease, have divergent roles. But a new study, led by researchers at the Department of Cellular and Molecular Medicine at the UC San Diego School of Medicine, shows that a common pathway links them.

The discovery reveals a small set of target genes that could be used to measure the health of motor neurons, and provides a useful tool for development of new pharmaceuticals to treat the devastating disorder, which currently has no treatment or cure.

Funded in part by the National Institutes of Health and the California Institute for Regenerative Medicine (CIRM), the study is published in the advance online edition of Nature Neuroscience on Sept. 30.

ALS is an adult-onset neurodegenerative disorder characterized by premature degeneration of motor neurons, resulting in a progressive, fatal paralysis in patients.

The two proteins that contribute to the disease — FUS/TLS and TDP-43 — bind to ribonucleic acid (RNA), intermediate molecules that translate genetic information from DNA to proteins. In normal cells, both TDP-43 and FUS/TLS are found in the nucleus where they help maintain proper levels of RNA. In the majority of ALS patients, however, these proteins instead accumulate in the cell’s cytoplasm — the liquid that separates the nucleus from the outer membrane, and thus are excluded from the nucleus, which prevents them from performing their normal duties.

Since the proteins are in the wrong location in the cell, they are unable to perform their normal function, according to the study’s lead authors, Kasey R. Hutt, Clotilde Lagier-Tourenne and Magdalini Polymenidou. “In diseased motor neurons where TDP-43 is cleared from the nucleus and forms cytoplasmic aggregates,” the authors wrote, “we saw lower protein levels of three genes regulated by TDP-43 and FUS/TLS. We predicted that this, based on our mouse studies, and found the same results in neurons derived from human embryonic stem cells.”

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How immune system, inflammation may play role in ALS

UCLA findings may offer new approach to reducing inflammation in Lou Gehrig’s disease.

ALS macrophages

In an early study, UCLAresearchers found that the immune cells of patients with amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s disease, may play a role in damaging the neurons in the spinal cord. ALS is a disease of the nerve cells in the brain and spinal cord that control voluntary muscle movement.

Specifically, the team found that inflammation instigated by the immune system in ALS can trigger macrophages — cells responsible for gobbling up waste products in the brain and body — to also ingest healthy neurons. During the inflammation process, motor neurons, whether healthy or not, are marked for clean-up by the macrophages.

In addition, the team found that a lipid mediator called resolvin D1, which is made in the body from the omega-3 fatty acid DHA, was able to “turn off” the inflammatory response that made the macrophages so dangerous to the neurons. Resolvin D1 blocked the inflammatory proteins being produced by the macrophages, curbing the inflammation process that marked the neurons for clean-up. It inhibited key inflammatory proteins like IL-6 with a potency 1,100 times greater than the parent molecule, DHA. DHA has been shown in studies to be neuroprotective in a number of conditions, including stroke and Alzheimer’s disease.

For the study, the team isolated macrophages from blood samples taken from both ALS patients and controls and spinal cord cells from deceased donors.


The study findings on resolvin D1 may offer a new approach to attenuating the inflammation in ALS. Currently, there is no effective way of administering resolvins to patients, so clinical research with resolvin D1 is still several years away. The parent molecule, DHA, is available in stores, although it has not been tested in clinical trials for ALS. Studies with DHA are in progress for Alzheimer’s disease, stroke and brain injury and have been mostly positive.


Senior author Dr. Milan Fiala, a researcher in the department of surgery at the David Geffen School of Medicine at UCLA, and first author Guanghao Liu, a UCLA undergraduate student, are available for interviews.


The study was privately funded by ALS patients.


The research appeared in the May 30 edition of the peer‑reviewed American Journal of Neurodegeneration. A copy of the full study is available.

Color images are available showing how a patient’s own immune cells impact neurons, as seen in the spinal cord of an ALS patient.

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Stem cell-derived neurotransmissions measured

UCLA research could shed light on a variety of neurodegenerative diseases, such as ALS.

Bennett Novitch, UCLA

In an effort to identify the underlying causes of neurological disorders that impair motor functions such as walking and breathing, UCLA researchers have developed a novel system to measure communication between stem cell-derived motor neurons and muscle cells in a Petri dish.

The study provides an important proof of principle that functional motor circuits can be created outside the body using these neurons and cells and that the level of communication, or synaptic activity, between them can be accurately measured by stimulating the motor neurons with an electrode and then tracking the transfer of electrical activity into the muscle cells to which the neurons are connected.

When motor neurons are stimulated, they release neurotransmitters that depolarize the membranes of muscle cells. This allows calcium and other ions to enter the cells, causing them to contract. By measuring the strength of this activity, one can get a good estimation of the overall health of motor neurons.

That estimation could shed light on a variety of neurodegenerative diseases, such as spinal muscular atrophy and amyotrophic lateral sclerosis (Lou Gehrig’s disease), in which communication between motor neurons and muscle cells is thought to unravel, said the study’s senior author, Bennett G. Novitch, an assistant professor of neurobiology and a scientist with the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.

The findings of the study appear May 4 in PLoS ONE, a peer-reviewed journal of the Public Library of Science.

“Now that we have this method to measure the strength of the communications between motor neurons and muscle cells, we may be able to begin exploring what happens in the earliest stages of motor neuron disease, before neuronal death becomes prevalent,” Novitch said. “This can help us to pinpoint where things begin to go wrong and provide us with new clues into therapeutic interventions that could improve synaptic communication and promote neuronal survival.”

Novitch said the synaptic communication activity his team was able to create and measure using muscle cells and motor neurons derived from mouse embryonic stem cells looks very similar to what is seen in a mouse, validating that their model is a realistic representation of what is happening in a living organism.

“That gives us a good starting point to try to model what happens in cells that harbor genetic mutations that are associated with neurodegenerative diseases,” he said. “To do that, we had to first define an activity profile of normal synaptic communication. Some research suggests that a breakdown in this communication can be an early indication of disease progression or possibly an initiating event. Neurons that cannot effectively transmit information to muscle cells will eventually withdraw their contacts, causing both the neurons and muscle cells to degenerate over time. Hopefully, we can now create disease models that will allow us to study what is happening.”

In this study, Novitch and his team, led by Joy Umbach, an associate professor of molecular and medical pharmacology at UCLA, used mouse embryonic stem cells to create the motor neurons, and they used previously established lines of muscle precursors to produce muscle fibers. They put both cells together in a Petri dish, and the cells were cultured in such a way as to encourage communication. Novitch said the team wanted to see if they would naturally form synaptic contacts and whether or not there was neural transmission between them.

In less than a week, the neurons had reached out to the muscle cells and assembled the protein networks needed for synaptic communication, Novitch said.

To measure the connections between the cells, the scientists used a technique called dual patch-clamp recording. Pipettes containing stimulating and recording electrodes are inserted into the membranes of the motor neurons and muscle cells, with special care being taken not to injure them. With this method, the researchers were able send an electrical current into the motor neurons and measure responses in the muscle cells, as well as visualize the muscular contractions.

“The in vitro system developed here might accordingly be expanded to assess the underlying cellular and molecular mechanisms that contribute to this decline in synaptic input to motor neurons,” the study states. “Thus, in addition to their utility for helping to answer fundamental biological questions, these co-cultures have clear applications in addressing problems of medical significance.”

Going forward, Novitch and his team hope to recreate and confirm the work using human stem cell-derived motor neurons and muscle cells and to measure the synaptic communications with newly developed optical recording methods, which are less invasive than the patch-clamp techniques used in this study.

The study was funded by the California Institute for Regenerative Medicine, the UCLA Broad Stem Cell Research Center, the Muscular Dystrophy Association, the UCLA Cellular and Molecular Biology Training Program, and the Ruth L. Kirschstein National Research Service Award.

The Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research: UCLA’s stem cell center was launched in 2005 with a UCLA commitment of $20 million over five years. A $20 million gift from the Eli and Edythe Broad Foundation in 2007 resulted in the renaming of the center. With more than 200 members, the Broad Stem Cell Research Center is committed to a multidisciplinary, integrated collaboration among scientific, academic and medical disciplines for the purpose of understanding adult and human embryonic stem cells. The center supports innovation, excellence and the highest ethical standards focused on stem cell research with the intent of facilitating basic scientific inquiry directed toward future clinical applications to treat disease. The center is a collaboration of the David Geffen School of Medicine at UCLA, UCLA’s Jonsson Cancer Center, the UCLA Henry Samueli School of Engineering and Applied Science and the UCLA College of Letters and Science.

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Insulin resistance, inflammation & a muscle-saving protein

UC San Diego explores complex interactions of lipids, inflammation in insulin resistance.

Christopher Glass, UC San Diego

In the online May 2 issue of the journal Cell Metabolism, researchers at the UC San Diego School of Medicine publish three distinct articles exploring:

  • the complex interactions of lipids and inflammation in insulin resistance
  • the roles of omega 3 fatty acids and a particular gene in fighting inflammation
  • how elevated levels of a particular protein might delay the muscle-destroying effects of amyotrophic lateral sclerosis.

Type 2 diabetes has reached epidemic proportions around the world, fueled in large part by the equally alarming expansion of obesity as a global health problem. But while it’s well-known that obesity is the most common cause of insulin resistance – the primary metabolic abnormality in type 2 diabetes – researchers have only recently begun to effectively parse the underlying, complicated relationships between lipids (fats and related molecules essential to cell structure and function) and chronic tissue inflammation (a key cause of obesity-induced insulin resistance).

In a wide-ranging perspective article published in Cell Metabolism, Christopher K. Glass, M.D., Ph.D., a professor in the departments of cellular and molecular medicine, and medicine at the UC San Diego, and Jerrold M. Olefsky, M.D., associate dean for scientific affairs and distinguished professor of medicine at UC San Diego, survey where the science stands, describing, for example, the pro-inflammatory effects of saturated fatty acids and the anti-inflammatory benefits of omega 3 fatty acids. They also discuss how inflammation impacts lipid metabolism at the cellular, tissue, organ and whole-body levels.

In a second, related article, Olefsky and colleague Da Young Oh, an assistant project scientist, discuss the critical role of a gene called GPR120 in inhibiting pro-inflammatory macrophages while simultaneously boosting the anti-inflammatory benefits of omega 3 fatty acids. They argue that new research highlights the importance of GPR120 as an attractive target for new drugs that could increase insulin sensitivity and, perhaps, have anti-obesity effects as well.

Finally, Don W. Cleveland, Ph.D., professor and chair of the Department of Cellular and Molecular Medicine and head of the Laboratory of Cell Biology at the Ludwig Institute for Cancer Research at UC San Diego and colleagues report the effects of elevated levels of a gene- regulating protein in mouse cells afflicted by a form of amyotrophic lateral sclerosis or ALS.

In humans, ALS is a progressive, adult-onset neurodegenerative disorder characterized by selective motor neuron and muscle loss that ultimately results in fatal paralysis. Among the key players in muscle function is a transcriptional activator protein called PGC-1alpha, which helps enhance various aspects of muscle cell function, including metabolism and mitochondrial biogenesis.

Cleveland and colleagues report that elevated levels of PGC-1alpha in the muscles of a mouse model of inherited ALS helps maintain health and function, though it does not extend survival time. The researchers suggest that increasing PCG-1alpha activity in muscle could be a new and attractive therapeutic target for maintaining, improving and extending physical abilities in ALS patients.

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