Links for Keyword: ALS-Lou Gehrig's Disease

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In two studies of mice, researchers showed that a drug, engineered to combat the gene that causes spinocerebellar ataxia type 2 (SCA2), might also be used to treat amyotrophic lateral sclerosis (ALS). Both studies were published in the journal Nature with funding from National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health. “Our results provide hope that we may one day be able to treat these devastating disorders,” said Stefan M. Pulst, M.D., Dr. Med., University of Utah, professor and chair of neurology and a senior author of one the studies. In 1996, Dr. Pulst and other researchers discovered that mutations in the ataxin 2 gene cause spinocerebellar ataxia type 2, a fatal inherited disorder that primarily damages a part of the brain called the cerebellum, causing patients to have problems with balance, coordination, walking and eye movements. For this study his team found that they could reduce problems associated with SCA2 by injecting mouse brains with a drug programmed to silence the ataxin 2 gene. In the accompanying study, researchers showed that injections of the same type of drug into the brains of mice prevented early death and neurological problems associated with ALS, a paralyzing and often fatal disorder. “Surprisingly, the ataxin 2 gene may act as a master key to unlocking treatments for ALS and other neurological disorders,” said Aaron Gitler, Ph.D., Stanford University, associate professor and senior author of the second study. In 2010, Dr. Gitler and colleagues discovered a link between ataxin 2 mutations and ALS.

Related chapters from BP7e: Chapter 11: Motor Control and Plasticity
Related chapters from MM:Chapter 5: The Sensorimotor System
Link ID: 23486 - Posted: 04.13.2017

Workplace exposure to electromagentic fields is linked to a higher risk of developing the most common form of motor neurone disease. Amyotrophic lateral sclerosis (ALS) is a disease that ravages the body’s nerve cells, leaving people unable to control their bodies. People can die as soon as two years after first experiencing symptoms. “Several previous studies have found that electrical workers are at increased risk of ALS,” says Neil Pearce, at the London School of Hygiene and Tropical Medicine. “We don’t know why the risk is higher, but the two most likely explanations involve either electrical shocks, or ongoing exposure to extremely low frequency magnetic fields.” Now an analysis of data from more than 58,000 men and 6,500 women suggests it is the latter. Roel Vermeulen, at Utrecht University in the Netherlands, and his team found that people whose jobs exposed them to high levels of very low frequency magnetic fields were twice as likely to develop ALS as people who have never had this kind of occupational exposure. Jobs with relatively highe extremely low frequency electromagnetic fields levels include electric line installers, welders, sewing-machine operators, and aircraft pilots, says Vermuelen. “These are essentially jobs where workers are placed in close proximity to appliances that use a lot of electricity.” © Copyright Reed Business Information Ltd.

Related chapters from BP7e: Chapter 11: Motor Control and Plasticity
Related chapters from MM:Chapter 5: The Sensorimotor System
Link ID: 23424 - Posted: 03.30.2017

By DENISE GRADY Dr. Lewis P. Rowland, a neurologist who made fundamental discoveries in nerve and muscle diseases and clashed with government investigators during the McCarthy era, died on March 16 in Manhattan. He was 91. The cause was a stroke, his son Steven said. Dr. Rowland, the chairman of Columbia University’s neurology department for 25 years, died at NewYork-Presbyterian/Columbia University Medical Center. Dr. Rowland was a prolific researcher and writer, with nearly 500 published scientific articles that focused on devastating neuromuscular diseases, including muscular dystrophy, myasthenia gravis and many rare syndromes. He took a special interest in amyotrophic lateral sclerosis, or A.L.S., also called Lou Gehrig’s disease, which causes degeneration of nerves in the brain and spinal cord, leading to weakness, paralysis and death. Dr. Rowland led research teams that delineated a number of uncommon diseases that had been poorly understood. They also found that in a subgroup of A.L.S. patients, the disease was linked to lymphoma, a cancer of the immune system. Other studies led to the discovery that a gene defect causes an unusual form of dementia in some patients with A.L.S. In myasthenia gravis, Dr. Rowland and his colleagues documented its high death rate and helped identify treatments that prolonged survival. In the 1970s, long before the tools existed to study DNA’s role in neurological diseases like A.L.S., Alzheimer’s and Parkinson’s, Dr. Rowland predicted correctly that genetics would be the key to understanding them. One of his accomplishments at Columbia was the expansion in 1982 of an intensive care unit that added beds for patients who were severely ill with neurological disorders. Before then, it was often difficult to find I.C.U. space for them. © 2017 The New York Times Company

Related chapters from BP7e: Chapter 11: Motor Control and Plasticity
Related chapters from MM:Chapter 5: The Sensorimotor System
Link ID: 23399 - Posted: 03.24.2017

A study in Neurology suggests that analyzing levels of the protein p75ECD in urine samples from people with amyotrophic lateral sclerosis (ALS) may help monitor disease progression as well as determine the effectiveness of therapies. The study was supported by National Institute of Neurological Disorders and Stroke (NINDS) and National Center for Advancing Translational Sciences (NCATS), both part of the National Institutes of Health. Mary-Louise Rogers, Ph.D., senior research fellow at Flinders University in Adelaide, Australia, and Michael Benatar, M.D., Ph.D, professor of neurology at the University of Miami, and their teams, discovered that levels of urinary p75 ECD increased gradually in patients with ALS as their disease progressed over a 2-year study period. “It was encouraging to see changes in p75ECD over the course of the study, because it suggests an objective new method for tracking the progression of this aggressive disease,” said Amelie Gubitz, Ph.D., program director at NINDS. “In addition, it indicates the possibility of assessing whether levels of that protein decrease while patients try future treatments, to tell us whether the therapies are having any beneficial effects.” Further analysis of the samples from 54 patients revealed that those who began the study with lower levels of urinary p75ECD survived longer than did patients who had higher levels of the protein initially, suggesting that it could be a prognostic marker of the disease and may inform patients about their illness. Dr. Benatar and his team noted that this may be useful in selecting participants for clinical trials and in improving study design.

Related chapters from BP7e: Chapter 11: Motor Control and Plasticity
Related chapters from MM:Chapter 5: The Sensorimotor System
Link ID: 23396 - Posted: 03.23.2017

By KATHRYN SHATTUCK After his short film screened at the Sundance Film Festival in 2008, a euphoric Simon Fitzmaurice was walking the snowy streets of Park City, Utah, when his foot began to hurt. Back home in Ireland that summer, by then dealing with a pronounced limp, he received a shattering diagnosis: motor neuron disease, or M.N.D. (more commonly known in the United States as A.L.S., or Lou Gehrig’s Disease), a neurological disorder that causes increasing muscle weakness and eventual paralysis and is, in most cases, fatal. The doctor gave Mr. Fitzmaurice, then 33, three or four years to live. That might have been the end of any normal existence. But Mr. Fitzmaurice, by his own measure a “bit of a stubborn bastard,” was determined to leave his wife, Ruth, and their two young sons — with a third on the way — a legacy other than self-pity. The result is Mr. Fitzmaurice’s first feature film, and perhaps his salvation — “My Name Is Emily.” The movie, which opened in limited release in the United States on Feb. 17, stars Evanna Lynch, the airy Luna Lovegood of “Harry Potter” fame, as a teenage outlier in both her Dublin foster home and high school who goes on the lam with her only friend (George Webster) to free her father (Michael Smiley) from a mental hospital. The film — with gorgeous scenes of Ms. Lynch plunged, nymphlike, into a cerulean sea or riding shotgun through the emerald countryside in a canary-yellow vintage Renault — won for best cinematography when it debuted at the Galway Film Fleadh in 2015. “I am not trying to prove anything,” Mr. Fitzmaurice wrote in an email, before quickly reconsidering. “Actually, I am trying to prove something. I remember thinking, ‘I must do this to show my children to never give up.’” Mr. Fitzmaurice was writing with his hands when he began the script for “My Name Is Emily.” By the time he was finished, he was writing with his eyes. © 2017 The New York Times Company

Related chapters from BP7e: Chapter 11: Motor Control and Plasticity
Related chapters from MM:Chapter 5: The Sensorimotor System
Link ID: 23275 - Posted: 02.24.2017

By Jessica Hamzelou Three people with paralysis have learned to type by thought alone using a brain implant – at the fastest speeds recorded using such a system. Two have motor neurone disease, also known as ALS – a degenerative disorder that destroys neurons associated with movement – while the other has a spinal cord injury. All three have weakness or paralysis in all of their limbs. There is a chance that those with ALS will eventually lose the ability to speak, too, says Jaimie Henderson, a neurosurgeon at Stanford University Medical Center in California. People who have lost the ability to talk may be offered devices that allow them to select letters on a screen using head, cheek or eye movements. This is how Stephen Hawking communicates, for example. But brain-machine interfaces are also being developed in the hope that they may one day be a more intuitive way of communicating. These involve reading brain activity, either externally or via an implant embedded in the brain, and turning it into a signal that can be used to direct something in the environment. At the moment, these devices are a little slow. Henderson and his colleagues wanted to make a device that was quicker and easier to use than those currently in trials. © Copyright Reed Business Information Ltd.

Related chapters from BP7e: Chapter 11: Motor Control and Plasticity
Related chapters from MM:Chapter 5: The Sensorimotor System
Link ID: 23264 - Posted: 02.22.2017

Many people think of fish and seafood as being healthy. However, new research suggests eating certain species that tend to have high levels of mercury may be linked to a greater risk of developing amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. Questions remain about the possible impact of mercury in fish, according to a preliminary study released Monday that will be presented at the American Academy of Neurology's 69th annual meeting in Boston in April. Fish and seafood consumption as a regular part of the diet was not associated with ALS, the study said. "For most people, eating fish is part of a healthy diet," said study author Elijah Stommel of Dartmouth College in Hanover, N.H., and a fellow of the academy. In addition, the authors said their study does not negate the fact that eating fish provides many health benefits. Instead, it suggests people may want to choose species that are known to have a lower mercury content, and avoid consuming fish caught in waters where there is mercury contamination. The researchers stressed that more research is needed before fish consumption guidelines for neurodegenerative illness can be made. While the exact cause of ALS is not known, some previous studies have suggested the neurotoxic metal to be a risk factor for ALS, a progressive neurological disease. ©2017 CBC/Radio-Canada.

Related chapters from BP7e: Chapter 11: Motor Control and Plasticity
Related chapters from MM:Chapter 5: The Sensorimotor System
Link ID: 23257 - Posted: 02.21.2017

By Timothy Revell It can be difficult to communicate when you can only move your eyes, as is often the case for people with ALS (also known as motor neurone disease). Microsoft researchers have developed an app to make talking with your eyes easier, called GazeSpeak. GazeSpeak runs on a smartphone and uses artificial intelligence to convert eye movements into speech, so a conversation partner can understand what is being said in real time. The app runs on the listener’s device. They point their smartphone at the speaker as if they are taking a photo. A sticker on the back of the phone, visible to the speaker, shows a grid with letters grouped into four boxes corresponding to looking left, right, up and down. As the speaker gives different eye signals, GazeSpeak registers them as letters. “For example, to say the word ‘task’ they first look down to select the group containing ‘t’, then up to select the group containing ‘a’, and so on,” says Xiaoyi Zhang, who developed GazeSpeak whilst he was an intern at Microsoft. GazeSpeak selects the appropriate letter from each group by predicting the word the speaker wants to say based on the most common English words, similar to predictive text messaging. The speaker indicates they have finished a word by winking or looking straight ahead for two seconds. The system also takes into account added lists of words, like names or places that the speaker is likely to use. The top four word predictions are shown onscreen, and the top one is read aloud. © Copyright Reed Business Information Ltd.

Related chapters from BP7e: Chapter 11: Motor Control and Plasticity
Related chapters from MM:Chapter 5: The Sensorimotor System
Link ID: 23248 - Posted: 02.18.2017

By STEPH YIN Researchers have designed a system that lets a patient with late-stage Lou Gehrig’s disease type words using brain signals alone. The patient, Hanneke De Bruijne, a doctor of internal medicine from the Netherlands, received a diagnosis of amyotrophic lateral sclerosis, also known as A.L.S. or Lou Gehrig’s disease, in 2008. The neurons controlling her voluntary muscles were dying, and eventually she developed a condition called locked-in syndrome. In this state, she is cognitively aware, but nearly all of her voluntary muscles, except for her eyes, are paralyzed, and she has lost the ability to speak. In 2015, a group of researchers offered an option to help her communicate. Their idea was to surgically implant a brain-computer interface, a system that picks up electrical signals in her brain and relays them to software she can use to type out words. “It’s like a remote control in the brain,” said Nick Ramsey, a professor of cognitive neuroscience at the University Medical Center Utrecht in the Netherlands and one of the researchers leading the study. On Saturday, the research team reported in The New England Journal of Medicine that Ms. De Bruijne independently controlled the computer typing program seven months after surgery. Using the system, she is able to spell two or three words a minute. “This is the world’s first totally implanted brain-computer interface system that someone has used in her daily life with some success,” said Dr. Jonathan R. Wolpaw, the director of the National Center for Adaptive Neurotechnologies in Albany. © 2016 The New York Times Company

Related chapters from BP7e: Chapter 11: Motor Control and Plasticity
Related chapters from MM:Chapter 5: The Sensorimotor System
Link ID: 22859 - Posted: 11.12.2016

Richard Harris Researchers have launched an innovative medical experiment that's designed to provide quick answers while meeting the needs of patients, rather than drug companies. Traditional studies can cost hundreds of millions of dollars, and can take many years. But patients with amyotrophic lateral sclerosis, or Lou Gehrig's disease don't have the time to wait. This progressive muscle-wasting disease is usually fatal within a few years. Scientists in an active online patient community identified a potential treatment and have started to gather data from the participants virtually rather than requiring many in-person doctor's visits. How is that possible? In this case, doctors and patients alike got interested in an extraordinary ALS patient whose symptoms actually got better, which rarely occurs. He'd been taking a dietary supplement called lunasin, "and lo and behold six months later, [his] speech [was] back to normal, swallowing back to normal, doesn't use his feeding tube, [and he was] significantly stronger as measured by his therapists," said Richard Bedlack, a neurologist who runs the ALS clinic at Duke University. Of course, it could just be a coincidence that the man who got better happened to be taking these supplements. To find out, Bedlack teamed up to run a study with Paul Wicks, a neuropsychologist and vice president for innovation at a web-based patient organization called PatientsLikeMe. © 2016 npr

Related chapters from BP7e: Chapter 11: Motor Control and Plasticity
Related chapters from MM:Chapter 5: The Sensorimotor System
Link ID: 22788 - Posted: 10.26.2016

Ian Sample and Nicky Woolf When Bill Gates pulled on a red and white-striped cord to upturn a bucket of iced water positioned delicately over his head, the most immediate thought for many was not, perhaps, of motor neurone disease. But the ice bucket challenge, the charity campaign that went viral in the summer of 2014 and left scores of notable persons from Gates and Mark Zuckerberg to George W. Bush and Anna Wintour shivering and drenched, has paid off in the most spectacular way. Dismissed by some at the time as “slacktivism” - an exercise that appears to do good while achieving very little - the ice bucket challenge raised more than $115m (£88m) for motor neurone disease in a single month. Now, scientists funded with the proceeds have discovered a gene variant associated with the condition. In the near term the NEK1 gene variant, described in the journal Nature Genetics this week, will help scientists understand how the incurable disorder, known also as Amyotrophic Lateral Sclerosis (ALS) or Lou Gehrig’s disease, takes hold. Once the mechanisms are more clearly elucidated, it may steer researchers on a path towards much-needed treatments. The work may never have happened were it not for the curious appeal of the frozen water drenchings. The research grants that scientists are awarded do not get close to the €4m the study required. Instead, Project MinE, which aims to unravel the genetic basis of the disease and ultimately find a cure, was funded by the ALS Association through ice bucket challenge donations. © 2016 Guardian News and Media Limited

Related chapters from BP7e: Chapter 11: Motor Control and Plasticity; Chapter 7: Life-Span Development of the Brain and Behavior
Related chapters from MM:Chapter 5: The Sensorimotor System; Chapter 13: Memory, Learning, and Development
Link ID: 22487 - Posted: 07.28.2016

Beatrice Alexandra Golomb, Statins can indeed produce neurological effects. These drugs are typically prescribed to lower cholesterol and thereby reduce the risk of heart attack and stroke. Between 2003 and 2012 roughly one in four Americans aged 40 and older were taking a cholesterol-lowering medication, according to the Centers for Disease Control and Prevention. But studies show that statins can influence our sleep and behavior—and perhaps even change the course of neurodegenerative conditions, including dementia. The most common adverse effects include muscle symptoms, fatigue and cognitive problems. A smaller proportion of patients report peripheral neuropathy—burning, numbness or tingling in their extremities—poor sleep, and greater irritability and aggression. Interestingly, statins can produce very different outcomes in different patients, depending on an individual's medical history, the statin and the dose. Studies show, for instance, that statins generally reduce the risk of ischemic strokes—which arise when a blocked artery or blood clot cuts off oxygen to a brain region—but can also increase the risk of hemorrhagic strokes, or bleeding into the brain. Statins also appear to increase or decrease aggression. In 2015 my colleagues and I observed that women taking statins, on average, showed increased aggression; men typically showed less, possibly because of reduced testosterone levels. Some men in our study did experience a marked increase in aggression, which was correlated with worsening sleep. © 2016 Scientific American

Related chapters from BP7e: Chapter 11: Motor Control and Plasticity; Chapter 7: Life-Span Development of the Brain and Behavior
Related chapters from MM:Chapter 5: The Sensorimotor System; Chapter 13: Memory, Learning, and Development
Link ID: 22419 - Posted: 07.11.2016

By Nicholas Bakalar Exposure to pesticides may increase the risk for amyotrophic lateral sclerosis, also known as Lou Gehrig’s disease, a new study has found. The study, in JAMA Neurology, included 156 patients with A.L.S. and 128 controls. All participants completed questionnaires providing information on age, sex, ethnicity, education, marital status, residential history, occupational history, smoking and military service. The researchers used the information on residence and occupation to estimate long-term exposure to pesticides, and then took blood samples to determine serum levels of 122 persistent environmental pollutants. The scientists divided exposure into four time periods: ever exposed, exposed in the last 10 years, exposed 10 to 30 years ago, and exposed more than 30 years ago. Exposure to pesticides at any time was associated with a fivefold increased relative risk for A.L.S. compared to no exposure. Even exposure more than 30 years ago tripled the risk. Military service was associated with double the risk, confirming findings of previous studies. “This is an association, not causality,” cautioned the senior author, Dr. Eva L. Feldman, a professor of neurology at the University of Michigan. “We found that people with A.L.S. were five times more likely to have been exposed to pesticides, but we don’t want people to conclude that pesticides cause A.L.S.” © 2016 The New York Times Company

Related chapters from BP7e: Chapter 11: Motor Control and Plasticity; Chapter 4: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology
Related chapters from MM:Chapter 5: The Sensorimotor System; Chapter 4: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology
Link ID: 22212 - Posted: 05.14.2016

The Chamorro people of the Pacific island of Guam know it as lytigo-bodig. For decades, they have been struck down by a mysterious illness that resembles the muscle-wasting disease amyotrophic lateral sclerosis (ALS), Parkinson’s disease and Alzheimer’s-like dementia. It now looks like we have a clue that could point to a way of slowing its development. Lytigo-bodig is a progressive disease. ALS symptoms arrive when people are in their mid-40s and early 50s. By the time they reach their 60s, they also have the shaking and lack of coordination that characterises Parkinson’s, before the cognitive problems associated with dementia also set in. “Initially they stumble a bit, but as their muscles wither, they need help with eating and going to the toilet, as well as having difficulty swallowing and breathing,” says Paul Cox of the Institute for Ethnomedicine in Wyoming. For a long time, a chemical called BMAA, found in the cycad seeds that the Chamorro grind up to make flour, has been suspected as the cause of the disease. The toxin builds up in the cyanobacteria that grow in the roots of cycad plants. It also accumulates in the tissue of seed-eating flying foxes, which the Chamorro hunt and eat. To see if they could confirm BMAA as the culprit, Cox fed fruit spiked with the toxin to vervet monkeys for 140 days. They estimated this was equivalent to the dose a typical islander might get over a lifetime. Although they didn’t show cognitive problems, the animals did develop brain abnormalities called tau tangles and deposits of amyloid plaque. The density and placement of these abnormalities were similar to those seen in the islanders. “The structure of the pathology is almost identical,” says Cox. “We were stunned.” © Copyright Reed Business Information Ltd.

Related chapters from BP7e: Chapter 11: Motor Control and Plasticity; Chapter 4: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology
Related chapters from MM:Chapter 5: The Sensorimotor System; Chapter 4: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology
Link ID: 21802 - Posted: 01.20.2016

Three teams of scientists supported by the National Institutes of Health showed that a genetic mutation linked to some forms of amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD) may destroy neurons by disrupting the movement of materials in and out of the cell’s nucleus, or command center where most of its DNA is stored. The results, published in the journals Nature and NatureNeuroscience, provide a possible strategy for treating the two diseases. “This research shines a spotlight on the role of nuclear transport in the health of neurons,” said Amelie Gubitz, Ph.D., program director at the NIH’s National Institute of Neurological Disorders and Stroke (NINDS). “The results provide new insights into how this mutation derails an essential process in neurons and opens new avenues for therapy development.” Both ALS and FTD are caused by the death of specific neurons. In ALS, this leads to movement difficulties and eventually paralysis, while in FTD, patients experience problems with language and decision making. Past research has connected a specific mutation in the C9orf72 gene to 40 percent of inherited ALS cases and 25 percent of inherited FTD cases, as well as nearly 10 percent of non-inherited cases of each disorder. The recent experiments, conducted in yeast, fruit flies, and neurons from patients, found that the mutation prevents proteins and genetic material called RNA from moving between the nucleus and the cytoplasm that surrounds it. “At the end of the day, this culminates in a defect in the flow of genetic information, which leads to problems expressing genes in the right place at the right time,” said J. Paul Taylor, M.D., Ph.D., a researcher at St. Jude’s Children’s Research Hospital in Memphis, Tennessee, and the senior author of one of the papers.

Related chapters from BP7e: Chapter 11: Motor Control and Plasticity
Related chapters from MM:Chapter 5: The Sensorimotor System
Link ID: 21524 - Posted: 10.17.2015

By Jon Cohen A virus that long ago spliced itself into the human genome may play a role in amyotrophic lateral sclerosis (ALS), the deadly muscle degenerative disease that crippled baseball great Lou Gehrig and ultimately took his life. That’s the controversial conclusion of a new study, which finds elevated levels of human endogenous retrovirus K (HERV-K) in the brains of 11 people who died from the disease. “This certainly is interesting and provocative work,” says Raymond Roos, a neurologist at the University of Chicago in Illinois who treats and studies ALS but who was not involved with the finding. Still, even the scientists behind the work caution that more research is needed to confirm the link. “I’m very careful to say HERV-K doesn’t cause the disease but may play a role in the pathophysiology,” says study leader Avindra Nath, a neuroimmunologist at the National Institute of Neurological Disorders and Stroke in Bethesda, Maryland. “The darn thing is in the chromosomes to begin with. It’s going to be very hard to prove causation.” It was another retrovirus, HIV, that led Nath to first suspect a connection between viruses and ALS. In 2006, he was helping a patient control his HIV infection with antiretroviral drugs when he noticed that the man’s ALS also improved. “That intrigued me, and I looked in the ALS literature and saw that people had reported they could see reverse transcriptase in the blood.” Reverse transcriptase, an enzyme that converts RNA to DNA, is a hallmark of retroviruses, which use it to insert copies of their genes into chromosomes of their hosts. © 2015 American Association for the Advancement of Science

Related chapters from BP7e: Chapter 11: Motor Control and Plasticity; Chapter 6: Evolution of the Brain and Behavior
Related chapters from MM:Chapter 5: The Sensorimotor System
Link ID: 21466 - Posted: 10.01.2015

A healthy motor neuron needs to transport its damaged components from the nerve-muscle connection all the way back to the cell body in the spinal cord. If it cannot, the defective components pile up and the cell becomes sick and dies. Researchers at the National Institutes of Health’s National Institute of Neurological Disorders and Stroke (NINDS) have learned how a mutation in the gene for superoxide dismutase 1 (SOD1), which causes ALS, leads cells to accumulate damaged materials. The study, published in the journal Neuron, suggests a potential target for treating this familial form of ALS. More than 12,000 Americans have ALS, also known as Lou Gehrig’s disease, and roughly 5-10 percent of them inherited a genetic mutation from a parent. These cases of familial ALS are often caused by mutations in the gene that codes for SOD1, an important enzyme located in the neuron’s mitochondria, the cell’s energy-producing structures. This mutation causes the death of motor neurons that control the patient’s muscles, resulting in progressive paralysis. “About 90 percent of the energy in the brain is generated by mitochondria,” said Zu-Hang Sheng, Ph.D., an NINDS scientist and the study’s senior author. “If the mitochondria aren’t healthy, they produce energy less efficiently; they can also release harmful chemicals called reactive oxygen species that cause cell death. As a consequence, mitochondrial damage can cause neurodegeneration.” In healthy neurons, storage containers called late endosomes collect damaged mitochondria and various destructive chemicals. A motor protein called dynein then transports the endosomes to structures called lysosomes, which use the chemicals to break down the endosomes. Dr. Sheng’s team discovered that this crucial process is faulty in nerve cells with SOD1 mutations because mutant SOD1 interferes with a critical molecule called snapin that hooks the endosome to the dynein motor protein.

Related chapters from BP7e: Chapter 11: Motor Control and Plasticity
Related chapters from MM:Chapter 5: The Sensorimotor System
Link ID: 21294 - Posted: 08.13.2015

Scientists at Mayo Clinic, Jacksonville, Florida 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, Lou Gehrig’s disease), both of which are caused by a mutation in the a gene called C9ORF72. The study was partially funded by the National Institutes of Health and published in the journal Science. More than 30,000 Americans live with ALS, which 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.

Related chapters from BP7e: Chapter 11: Motor Control and Plasticity; Chapter 7: Life-Span Development of the Brain and Behavior
Related chapters from MM:Chapter 5: The Sensorimotor System; Chapter 13: Memory, Learning, and Development
Link ID: 20964 - Posted: 05.21.2015

By Brady Dennis In recent months, Pasadena-based Genervon has galvanized many patients with ALS by repeatedly touting the results of 12-week, 12-person trial involving the company's drug, GM604. The company asserted its early results were “statistically significant,” “very robust” and “dramatic.” It also has said it "submitted an accelerated approval application" to the FDA which, if approved, "would allow immediate access" to patients with ALS, also known as Lou Gehrig's disease. But the Wall Street Journal reported Monday that Genervon said in an email that it is “at the point of communicating with FDA about whether [the agency] would accept our formal application” for accelerated approval. In other words, the company has not yet submitted a New Drug Application, a step needed to officially set the FDA approval process in motion. The company's acknowledgement that it has not filed an NDA appears to contradict earlier press releases and statements made by the firm's owners, Winston and Dorothy Ko -- or at least to have sown confusion about the actual status of GM604. In one February press release, for example, the company said that in a meeting with the FDA, "three times during the one-hour meeting we requested that the FDA grant GM604 accelerated approval." Asking, however, is not the same as filing the necessary paperwork and the accompanying data required for the FDA to accept it as sufficient. The difference might seem to be a matter of semantics. But the real-world consequence is that, if Genervon has no application pending at the FDA, there is no imminent decision for the FDA to make about approving GM604.

Related chapters from BP7e: Chapter 11: Motor Control and Plasticity
Related chapters from MM:Chapter 5: The Sensorimotor System
Link ID: 20833 - Posted: 04.22.2015

By Amy Ellis Nutt and Brady Dennis For people with amyotrophic lateral sclerosis, which attacks the body’s motor neurons and renders a person unable to move, swallow or breathe, the search for an effective treatment has been a crushing disappointment. The only drug available for the disease, approved two decades ago, typically extends life just a few months. Then in the fall, a small California biotech company named Genervon began extolling the benefits of GM604, its new ALS drug. In an early-stage trial with 12 patients, the results were “statistically significant,” “very robust” and “dramatic,” the company said in news releases. Such enthusiastic pronouncements are unusual for such a small trial. In February, Genervon took an even bolder step: It applied to the Food and Drug Administration for “accelerated approval,” which allows promising treatments for serious or life-threatening diseases to bypass costly, large-scale efficacy trials and go directly to market. ALS patients responded by pleading with the FDA, in emotional videos and e-mails, to grant broad access to the experimental drug. Online forums lit up, and a Change.org petition calling for rapid approval attracted more than a half-million signatures. “Why would anyone oppose it?” asked ALS patient David Huntley in a letter read aloud in the past week at a rally on Capitol Hill. Huntley, a former triathlete, can no longer speak or travel, so his wife, Linda Clark, flew from San Diego to speak for him.

Related chapters from BP7e: Chapter 11: Motor Control and Plasticity
Related chapters from MM:Chapter 5: The Sensorimotor System
Link ID: 20752 - Posted: 04.04.2015