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By Pam Belluck One of the few treatments the Food and Drug Administration has approved for amyotrophic lateral sclerosis has failed a large clinical trial, and its manufacturer said Friday that it was considering whether to withdraw it from the market. The medication, called Relyvrio, was approved less than two years ago, despite questions about its effectiveness in treating the severe neurological disorder. At the time, the F.D.A.’s reviewers had concluded there was not yet sufficient evidence that the medication could help patients live longer or slow the rate at which they lose functions like muscle control, speaking or breathing without assistance. But the agency decided to greenlight the medication instead of waiting two years for results of a large clinical trial, citing data showing the treatment to be safe and the desperation of patients with a disease that often causes death within two to five years. Since then, about 4,000 patients in the United States have received the treatment, a powder that is mixed with water and either drunk or ingested through a feeding tube and carries a list price of $158,000 a year. Now, results of the 48-week trial of 664 patients are in, and they showed that the treatment did not work better than a placebo. “We are surprised and deeply disappointed,” Justin Klee and Joshua Cohen, the co-chief executive officers of Amylyx Pharmaceuticals, the treatment’s manufacturer, said in a statement. They said they would announce their plans for the medication within eight weeks, “which may include voluntarily withdrawing” it from the market. “We will be led in our decisions by two key principles: doing what is right for people living with A.LS., informed by regulatory authorities and the A.L.S. community, and by what the science tells us,” Mr. Klee and Mr. Cohen said. There are only two other approved A.L.S. medications in the United States: riluzole, approved in 1995, which can extend survival by several months, and edaravone, approved in 2017, which can slow progression by about 33 percent. © 2024 The New York Times Company

Related chapters from BN: Chapter 11: Motor Control and Plasticity
Related chapters from MM:Chapter 5: The Sensorimotor System
Link ID: 29186 - Posted: 03.09.2024

Juana Summers On a recent crisp June night, as the Chicago Cubs prepare to take on the Pittsburgh Pirates, fans dressed in blue pack Wrigley Stadium's famous bleachers. Sitting in his wheelchair, 42-year-old Brian Wallach looks out over the park, rooting for a very particular outcome that has nothing to do with baseball. He has amyotrophic lateral sclerosis (ALS) — sometimes referred to as Lou Gehrig's disease, named for the baseball legend once dubbed the "iron horse" because of his durability, before the disease took his life. At the gates of the stadium, ballpark staff hand out bright blue T-shirts with the Cubs logo and the words, "End ALS for Lou." The night is part of a growing movement to highlight ALS and spread awareness of the toll it has wrought on people. Wallach and his wife Sandra Abrevaya watch a Cubs game at Wrigley Field in June. Jamie Kelter Davis for NPR For Wallach, a former assistant U.S. attorney who once worked for Barack Obama, his specialty is turning that goodwill into action in the ALS community, the halls of Congress and the Oval Office. And he has used his connections to change the face of medical advocacy in this country. Wallach was diagnosed six years ago, on the day that he and his wife, Sandra Abrevaya, brought the newborn second daughter home from the hospital. "Sandra and I cried and we held our family tight. We did so because being diagnosed with ALS today is a death sentence. There is no cure. I will not see my daughters grow up," Wallach told Congress during testimony he gave in 2019. © 2023 npr

Related chapters from BN: Chapter 11: Motor Control and Plasticity
Related chapters from MM:Chapter 5: The Sensorimotor System
Link ID: 28837 - Posted: 07.01.2023

By Rebecca Robbins The Food and Drug Administration on Tuesday authorized the first drug for a rare genetic form of the neurological disorder A.L.S., despite uncertainty about the treatment’s effectiveness. The decision reflects the agency’s push toward greater flexibility in approving treatments for patients with devastating illnesses and few, if any, options. Biogen, the pharmaceutical company bringing the drug to market, said it would price the drug “within a range comparable to other recently launched A.L.S. treatments.” An A.L.S. therapy approved last year was priced at $158,000 annually. The drug, which is known scientifically as tofersen and will be sold under the brand name Qalsody, targets a mutation in a gene known as SOD1 that is present in about 2 percent of the roughly 6,000 cases of A.L.S. diagnosed in the United States each year. Fewer than 500 people in the United States at any given time are expected to be eligible. The agency authorized the treatment via a policy that allows a drug to be fast-tracked onto the market under certain circumstances before there is conclusive proof that it works. Biogen will be required to provide confirmatory evidence, from ongoing clinical research, to keep the drug on the market. The decision is the first conditional approval granted for a medication for A.L.S., or amyotrophic lateral sclerosis, which generally causes paralysis and death within a few years. Fewer than half the patients eligible for Qalsody survive more than three years after their diagnosis. The approval is based on evidence that the drug can significantly reduce levels of a protein that has been linked to damage to nerve cells. Biogen has argued that these results are reasonably likely to help patients, even though the drug, in a clinical trial, did not significantly slow the progression of the disease, as measured by patients’ ability to speak, swallow and perform other activities of daily living. © 2023 The New York Times Company

Related chapters from BN: Chapter 11: Motor Control and Plasticity
Related chapters from MM:Chapter 5: The Sensorimotor System
Link ID: 28753 - Posted: 04.26.2023

Asher Mullard The US Food and Drug Administration (FDA) is set to rule soon on the approval of a new drug for a rare form of amyotrophic lateral sclerosis (ALS). The hotly anticipated decision is expected to signpost the agency’s vision for neurological drugs — and its willingness to be flexible in the regulation of these therapeutics. People with the disease desperately need new treatments, because they face a degenerative condition that causes neuronal death and typically leads to fatal respiratory failure within three years of symptoms appearing1. Tofersen, developed by the biotechnology firms Biogen in Cambridge, Massachusetts, and Ionis Pharmaceuticals in Carlsbad, California, did not slow patients’ decline in a phase III trial2. However, some say the trial was too short, and point out that there were signs of possible benefit, such as a reduction in a biomarker of neuronal damage and death called neurofilament light chain (NFL). Because of this, Biogen has asked the FDA to approve the drug on an ‘accelerated’ basis, to fast-track it to patients with a guarantee that future trial data will determine whether it works. If approved, tofersen will become the latest example of the agency’s evolving approach to neurological drug development, which could boost industry investment in brain diseases. A vote of confidence for the drug would also supercharge interest in using NFL as a tool to measure brain health and to test drugs in future. “This could be the start of a new era,” says Valentina Bonetto, a neuroscientist at the Mario Negri Institute for Pharmacological Research in Milan, Italy. In March, the FDA convened a panel to discuss the tofersen data set. Its nine independent advisers rallied behind accelerated approval for the drug, voting unanimously that the available evidence supports a “reasonably likely” chance that tofersen will help people with SOD1 ALS. This rare disease is caused by genetic mutations that affect the protein SOD1, leading it to form toxic clumps in motor neurons in the brain, brainstem and spinal cord. The agency usually follows the recommendations of its advisory committee. © 2023 Springer Nature Limited

Related chapters from BN: Chapter 11: Motor Control and Plasticity; Chapter 15: Emotions, Aggression, and Stress
Related chapters from MM:Chapter 5: The Sensorimotor System; Chapter 11: Emotions, Aggression, and Stress
Link ID: 28744 - Posted: 04.18.2023

By Pam Belluck A new medication for A.L.S., the devastating neurological disorder that causes paralysis and death, will have a list price of $158,000 a year, its manufacturer disclosed Friday. The treatment, to be marketed as Relyvrio, is a combination of two existing drugs and will be available to patients in the United States in about four to six weeks, according to officials of the company, Amylyx Pharmaceuticals. Relyvrio was approved by the Food and Drug Administration on Thursday, even though the agency’s analysis concluded there was not yet sufficient evidence that the medication could help patients live longer or slow the rate at which they lose functions like muscle control, speaking or breathing without assistance. The F.D.A. decided to greenlight the drug instead of waiting until 2024 for results of a large clinical trial partly because the treatment is considered to be safe. The agency said that although the evidence of effectiveness was uncertain, “given the serious and life-threatening nature of A.L.S. and the substantial unmet need, this level of uncertainty is acceptable in this instance.” A.L.S., or amyotrophic lateral sclerosis — also called Lou Gehrig’s disease — often strikes patients in the prime of life and frequently causes death within two to five years. It is diagnosed in about 6,000 people worldwide each year, and Amylyx estimates that there are about 29,000 people living with the disease in the United States. Amylyx officials predicted that most patients would pay little or nothing for the treatment because the company expects insurers, both private and public, to cover it. Amylyx plans to provide it free to uninsured patients experiencing financial hardship. Still, the list price is much higher than that recommended by the Institute for Clinical and Economic Review, a nonprofit organization that evaluates the value of medicines. In a statement, the group’s chief medical officer, Dr. David Rind, said that while “there are clear benefits to patients with a rapidly fatal disease to have early access to a safe therapy,” his organization had concluded that “an annual price of $9,100 to $30,700 would be reasonable if the therapy actually works.” © 2022 The New York Times Company

Related chapters from BN: Chapter 11: Motor Control and Plasticity
Related chapters from MM:Chapter 5: The Sensorimotor System
Link ID: 28495 - Posted: 10.01.2022

By Laurie McGinley Independent advisers to the Food and Drug Administration on Wednesday voted 7 to 2 to recommend approval of an experimental ALS drug with strong support from patients and advocates, making it likely the hotly debated treatment will be cleared by the agency within weeks. The vote was a stunning turnaround from late March when the panel voted 6 to 4 to recommend against FDA approval. At that meeting, the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee concluded the evidence from a single clinical trial — with just 137 patients and some follow-up data — was not sufficient to show the drug, called AMX0035, slowed a degenerative disease that usually kills people within three to five years. But on Wednesday, after hours of discussion, several advisers said that additional analyses submitted by the drug’s manufacturer, Cambridge-based Amylyx, bolstered the case for approval, even though uncertainties remain. Advisers were also affected by the disease’s severity and the lack of effective treatments. A vow by a top Amylyx official to pull the drug from the market if a larger study, with 600 patients, fails to show effectiveness was also a factor in the vote. The FDA, which usually follows the recommendation of its outside advisers but is not required to, is expected to decide whether to approve the drug by Sept. 29. The improved fortunes of the medicine came despite criticism from FDA staff as recently as last week about the treatment’s effectiveness, the conduct of its clinical trial and the researchers’ interpretation of the data. But the medicine is considered safe, and the agency has been under intense pressure from ALS patients and physicians who say the treatment holds promise for a fatal disease that typically causes rapid deterioration and death.

Related chapters from BN: Chapter 11: Motor Control and Plasticity
Related chapters from MM:Chapter 5: The Sensorimotor System
Link ID: 28467 - Posted: 09.10.2022

Researchers have published two papers describing how they identified a potential new pathway for treating a sporadic form of amyotrophic lateral sclerosis (ALS). The studies were published as part of a cooperative research agreement between the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health, and the Switzerland-based biotechnology company GeNeuro Inc. One unusual side effect of hundreds of thousands of years of evolution is that the human genome now contains DNA sequences from ancient retroviruses—referred to as human endogenous retroviruses (HERVs). Though most remain dormant, reactivation of HERVs have been implicated in several neurodegenerative diseases, including ALS. The first of these papers shows that a specific HERV produces a protein that can be found in the cerebrospinal fluid (CSF) of people with ALS. This protein, called HERV-K ENV, is toxic when added to neurons grown in laboratory dishes. In addition, a special kind of mouse genetically designed to create HERV-K ENV develops symptoms very similar to ALS. Adding the CSF from people with ALS to lab-grown neurons resulted in damage to the cells. When a synthetic antibody designed specifically to recognize HERV-K ENV was added as well to those neurons, the toxic effects were reduced. These findings together suggest that the improper activation of the HERV-K ENV gene could be the cause of the symptoms seen in certain cases of sporadic ALS. The discovery that a synthetic antibody to HERV-K ENV could be protective led the researchers to look at whether the immune system of people with ALS produced any antibodies, as well. In the second paper, the authors show that indeed higher levels of antibodies against HERV-K ENV were seen in the blood of a group of people with ALS as compared to healthy donors. The pattern of antibodies against this viral protein was also more complex in persons with ALS. In addition, there was also a correlation between higher antibody levels against HERV-K ENV and longer overall survival.

Related chapters from BN: Chapter 11: Motor Control and Plasticity
Related chapters from MM:Chapter 5: The Sensorimotor System
Link ID: 28455 - Posted: 08.31.2022

By Pam Belluck An experimental therapy for A.L.S., the paralyzing and fatal neurological disorder, has been approved in Canada, adding a new treatment option for a disease for which there are few effective therapies. The approval, the first in the world for the treatment — AMX0035, to be marketed in Canada as Albrioza — comes with the condition that the drug company later provide better evidence that the treatment works. It is likely to be of major interest to patients with A.L.S. (amyotrophic lateral sclerosis) in the United States, where the same therapy is being evaluated by the Food and Drug Administration, which has raised questions about the treatment’s effectiveness. An F.D.A. review earlier this year found the treatment to be safe, but said there was not enough evidence that it was effective either in helping patients live longer or slowing the rate at which they lose functions like muscle control, speaking or breathing without assistance. A committee of independent advisers to the F.D.A. voted by a narrow margin in March that the therapy was not ready for approval. The F.D.A. had been scheduled to issue a final decision this month, but recently extended the deadline to Sept. 29, saying it needed more time to review additional analyses of data submitted by the company. In the meantime, Calaneet Balas, president and chief executive of the A.L.S. Association, one of several patient advocacy organizations pressing for F.D.A. approval, said, “We expect that Americans living with A.L.S. will try to access Albrioza in Canada, just as we have heard reports of people trying to buy the ingredients on Amazon.” © 2022 The New York Times Company

Related chapters from BN: Chapter 11: Motor Control and Plasticity
Related chapters from MM:Chapter 5: The Sensorimotor System
Link ID: 28369 - Posted: 06.14.2022

Linda Geddes A completely locked-in patient is able to type out words and short sentences to his family, including what he would like to eat, after being implanted with a device that enables him to control a keyboard with his mind. The findings, published in Nature Communications, overturn previous assumptions about the communicative abilities of people who have lost all voluntary muscle control, including movement of the eyes or mouth, as well as giving a unique insight into what it’s like to be in a “locked in” state. Locked-in syndrome – also known as pseudocoma - is a rare condition, where people are conscious and can see, hear, and smell, but are unable to move or speak due to complete paralysis of their voluntary muscles, eg as a result of the progressive neurodegenerative disease amyotrophic lateral sclerosis (ALS). Advertisement Some can communicate by blinking or moving their eyes, but those with completely locked-in syndrome (CLIS) cannot even control their eye muscles. In 2017, doctors at the University of Tübingen in Germany enabled three patients with CLIS to answer “yes” or “no” to questions by detecting telltale patterns in their brain activity, using a technology called functional near-infrared spectroscopy (fNIRS). The advance generated widespread media coverage, and prompted the parents of the current patient, who was diagnosed with ALS in 2015, to write to the medical team, saying he was losing the ability to communicate with his eye movements, and could they help. The problem with using fNIRS to help CLIS patients to communicate is that it is relatively slow, and only gives the correct answer 70% of the time, meaning questions have to be repeated to get a reliable answer. “It was always our goal to enable a patient in a completely locked down state to spell out words, but with a classification accuracy of 70%, it is almost impossible to enable free spelling,” said Dr Ujwal Chaudhary, a biomedical engineer and managing director of ALS Voice gGmbH in Mössingen, Germany, who co-led the research. © 2022 Guardian News & Media Limited

Related chapters from BN: Chapter 2: Functional Neuroanatomy: The Cells and Structure of the Nervous System; Chapter 11: Motor Control and Plasticity
Related chapters from MM:Chapter 2: Neurophysiology: The Generation, Transmission, and Integration of Neural Signals; Chapter 5: The Sensorimotor System
Link ID: 28250 - Posted: 03.23.2022

Christopher McDermott, MBChB, FRCP, PhD Early in my clinical practice, my team and I subscribed to the traditional view of ALS: the disease was either familial or sporadic. People with “familial” ALS had some family history of ALS (and therefore a possible genetic component), while people with “sporadic” disease did not have a family history.1 But that view began to change with the discovery that mutations (or changes) in a gene called C9orf72 could play a role in both the sporadic and familial types of ALS. Over time, we learned that this one mutation accounted for approximately 40% of familial ALS cases. Even more surprising: it accounted for close to 10% of cases in people with no family history of ALS—people previously believed to have the sporadic form of the disease. As this story unfolded, we began to question our old assumptions about familial and sporadic ALS, and we realized that just asking our patients about their family history wasn’t enough. C9orf72 has been associated with other neurologic diseases as well, so now, I and other ALS specialists understood that someone with a family history of related conditions might also have a genetic cause for their ALS. At the same time, other genetic mutations were being found in people with no family history of the disease and whose ALS had seemingly appeared out of nowhere.1 It was becoming clear that some people with what we often referred to as sporadic ALS could actually have a genetic component to their disease.1 My own research supported this belief. The Sheffield Institute for Translational Neuroscience, where we help develop and study new therapies for neuromuscular diseases, had an extensive biobank of samples from people with ALS. As new genetic mutations were discovered, our researchers tested these samples and found that many people who we thought had sporadic ALS in fact had one or more genetic mutations. © 2013-2021 All rights reserved.

Related chapters from BN: Chapter 11: Motor Control and Plasticity
Related chapters from MM:Chapter 5: The Sensorimotor System
Link ID: 27885 - Posted: 07.03.2021

Ian Sample Science editor Regular strenuous exercise raises the risk of developing motor neurone disease (MND) in people who are genetically predisposed to the condition, researchers say. Scientists at the University of Sheffield found a causal relationship between high intensity physical activity and the disorder among those already susceptible to the disease. They believe the work marks a major step towards understanding the link between intense exercise, which may contribute to motor neurone injury in certain people, and the neurodegenerative disease, which affects about 5,000 individuals in the UK. “We have suspected for some time that exercise was a risk factor for MND, but until now this link was considered controversial,” said Dr Johnathan Cooper-Knoc, a neurologist at Sheffield. “This study confirms that in some people, frequent strenuous exercise leads to an increase in the risk of MND.” The life-time risk of developing MND is about 1 in 400, but previous studies have suggested it is six times greater in professional football players compared with the general population. A number of high-profile British sportsmen have shared their experience with MND in recent years, including rugby league’s Rob Burrow, rugby union’s Doddie Weir and the the footballer Stephen Darby. The Sheffield researchers emphasise that the vast majority of people who undertake vigorous exercise do not develop MND, and that their next step is to develop tests that identify people most at risk. © 2021 Guardian News & Media Limited

Related chapters from BN: Chapter 11: Motor Control and Plasticity
Related chapters from MM:Chapter 5: The Sensorimotor System
Link ID: 27848 - Posted: 06.11.2021

Michelle Andrews Once the rules for implementing it are worked out, a bill signed into federal law in December will eliminate the required five-month waiting period for diagnosed ALS patients to begin disability benefits, enabling quicker Medicare coverage as well. LumiNola/Getty Images Anita Baron first noticed something was wrong in August 2018, when she began to drool. Her dentist chalked it up to a problem with her jaw. Then her speech became slurred. She managed to keep her company going — it offers financing to small businesses — but working became increasingly difficult for her as her speech worsened. Finally, nine months, four neurologists and countless tests later, Baron, now 66, got a diagnosis: amyotrophic lateral sclerosis. ALS, often called Lou Gehrig's disease after the New York Yankees first baseman who died of the disease in 1941, destroys motor neurons, causing people to lose control of their limbs, their speech and, ultimately, their ability to breathe. It's usually fatal in two to five years, though about 10% of people survive ten years or more. People with ALS often must quit their jobs — and sometimes their spouses do, too, to provide care — leaving families in financial distress. A decade-long campaign by advocates highlighting this predicament notched a victory last month when Congress passed a bill opening key support programs earlier for ALS patients. © 2021 npr

Related chapters from BN: Chapter 11: Motor Control and Plasticity
Related chapters from MM:Chapter 5: The Sensorimotor System
Link ID: 27652 - Posted: 01.20.2021

A study led by researchers at the National Institutes of Health has made a surprising connection between frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), two disorders of the nervous system, and the genetic mutation normally understood to cause Huntington’s disease. This large, international project, which included a collaboration between the National Institute of Neurological Disorders and Stroke (NINDS) and the National Institute on Aging (NIA), opens a potentially new avenue for diagnosing and treating some individuals with FTD or ALS. Several neurological disorders have been linked to “repeat expansions,” a type of mutation that results in abnormal repetition of certain DNA building blocks. For example, Huntington’s disease occurs when a sequence of three DNA building blocks that make up the gene for a protein called huntingtin repeats many more times than normal. These repeats can be used to predict whether someone will develop the illness and even when their symptoms are likely to appear, because the more repeats in the gene, the earlier the onset of disease. “It has been recognized for some time that repeat expansion mutations can give rise to neurological disorders,” said Sonja Scholz, M.D., Ph.D., investigator, NINDS Intramural Research Program. “But screening for these mutations throughout the entire genome has traditionally been cost-prohibitive and technically challenging.” Taking advantage of technology available at NIH, the researchers screened the entire genomes from large cohorts of FTD/ALS patients and compared them to those of age-matched healthy individuals. While several patients had a well-established genetic marker for FTD/ALS, a small subset surprisingly had the same huntingtin mutation normally associated with Huntington’s disease. Remarkably, these individuals did not show the classical symptoms of Huntington’s but rather those of ALS or FTD.

Related chapters from BN: Chapter 11: Motor Control and Plasticity
Related chapters from MM:Chapter 5: The Sensorimotor System
Link ID: 27604 - Posted: 12.05.2020

By Concepción de León Pat Quinn, who helped raise $220 million to fight amyotrophic lateral sclerosis, or A.L.S., by promoting the Ice Bucket Challenge in 2014, died on Sunday, seven years after he learned he had the disease. He was 37. His death, at St. John’s Riverside Hospital in Yonkers, N.Y., was confirmed by the A.L.S. Association and in a post on his official Facebook page. Mr. Quinn did not create the challenge, in which people dumped buckets of ice water on their heads while pledging to donate money to fight A.L.S. But he and his friend Pete Frates, who also had A.L.S., are credited with amplifying it and helping to make it a sensation in the summer and fall of 2014, raising tens of millions of dollars for research and, perhaps nearly as important, wider awareness of the disease. “Pat changed the trajectory of the fight against A.L.S. forever,” Calaneet Balas, the president and chief executive of the A.L.S. Association, said in a statement on Sunday. “He inspired millions to get involved and care about people who are living with A.L.S.” A.L.S., also called Lou Gehrig’s disease, is a progressive neurodegenerative disorder that attacks the nerve cells that control voluntary muscle movements and leads to full paralysis. People with the disease typically live three to five years from the time of diagnosis, according to the National Institute of Neurological Disorders and Stroke. Shortly after Mr. Quinn learned he had A.L.S. in 2013, he created Quinn for the Win, a Facebook group, to raise awareness of the disease and to raise money to fight for a cure. Mr. Frates created his own page, Team Frate Train, with the same goal. In July 2014, Mr. Quinn and Mr. Frates saw another A.L.S. patient, Anthony Senerchia, do the Ice Bucket Challenge online. They created their own ice-bucket videos and shared the challenge with their followers. (Mr. Frates died last year at age 34.) In Her Words: Where women rule the headlines. From there, the campaign spread wildly, with Lady Gaga, Oprah Winfrey, LeBron James and scores of other celebrities participating and donating to the cause. The challenge raised $115 million for the A.L.S. Association and $220 million around the world for A.L.S. research in the span of just six weeks, the A.L.S. Association said. © 2020 The New York Times Company

Related chapters from BN: Chapter 11: Motor Control and Plasticity
Related chapters from MM:Chapter 5: The Sensorimotor System
Link ID: 27596 - Posted: 11.30.2020

By Sam Roberts Chris Pendergast, a Long Island teacher who defied the odds by surviving 27 years with Lou Gehrig’s disease, leading marathon “rides for life” for hundreds of miles from his motorized wheelchair to publicize the plight of fellow patients and raise $10 million for research, died on Oct. 14 at his home in Miller Place, N.Y. He was 71. His wife, Christine Pendergast, said the cause was complications of amyotrophic lateral sclerosis, the medical term for the disease that ended the career of Gehrig, the Yankee first baseman who, after playing in 2,130 consecutive games, proclaimed himself “the luckiest man on the face of the earth.” Gehrig died two years later, shortly before his 38th birthday. Mr. Pendergast was a 44-year-old teacher of gifted students at Dickinson Avenue elementary school in East Northport, on Long Island, when his eyes and hands began twitching and he started getting muscle spasms. On Oct. 13, 1993, he received the diagnosis: He had A.L.S., a degenerative disease, which diminishes muscle function and eventually the ability to breathe. The prognosis: He had three to five years to live. But Mr. Pendergast proved to be indomitable. He recast himself as the disease’s self-described squeaky wheel — “Since there’s no surviving constituency for A.L.S., there’s no squeaky wheel,” he told The New York Times in 2008. He founded the A.L.S. Ride for Life in 1997. The following year it mounted a 350-mile, two-week cavalcade from Yankee Stadium in the Bronx to Washington, with Mr. Pendergast leading it from his wheelchair. Subsequent annual rides went from Long Island’s East End to Manhattan with a small group of fellow patients. “We are dying men riding for life,” he told The Baltimore Sun in 2000. © 2020 The New York Times Company

Related chapters from BN: Chapter 11: Motor Control and Plasticity
Related chapters from MM:Chapter 5: The Sensorimotor System
Link ID: 27557 - Posted: 10.31.2020

By Pam Belluck A potential therapy for amyotrophic lateral sclerosis, a fatal neurological disorder, may allow patients to live several months longer than they otherwise would have, according to a study published Friday. The two-drug combination, dreamed up by two college students, is one of several potential treatments raising the hopes of patients with A.L.S., also known as Lou Gehrig’s disease. The paralytic condition steals people’s ability to walk, speak, eat and ultimately breathe, typically causing death within two to five years. There are only two approved A.L.S. medications, neither tremendously effective. But advocacy efforts by patients and organizations, along with the Ice Bucket Challenge, a highly successful fundraising campaign, have galvanized research into more than 20 therapies that are currently in clinical trials. The two-drug combination, called AMX0035, was conceived seven years ago by Joshua Cohen and Justin Klee, then a junior and senior at Brown University, with the goal of preventing the destruction of neurons that occurs in many brain disorders. It is a combination of an existing supplement and a medication for a pediatric urea disorder. Last month, a study of 137 patients reported that AMX0035 slowed progression of A.L.S. paralysis by about 25 percent more than a placebo. Measuring patients using a scale of physical function, researchers found that those receiving a placebo declined in 18 weeks to a level that patients receiving the treatment didn’t reach until 24 weeks, according to the study’s principal investigator, Dr. Sabrina Paganoni. But because that trial was conducted for only 24 weeks, it left unanswered a crucial question of whether the treatment extended survival for the patients receiving the therapy. After that study ended, 98 of the participants, who had not been told whether they had received placebo or therapy, were given the option of taking the therapy for up to 30 months, a format called an open-label extension study. © 2020 The New York Times Company

Related chapters from BN: Chapter 11: Motor Control and Plasticity
Related chapters from MM:Chapter 5: The Sensorimotor System
Link ID: 27533 - Posted: 10.19.2020

By Pam Belluck Seven years ago, Joshua Cohen, then a junior at Brown University majoring in biomedical engineering, was captivated by the question of why people develop brain disorders. “How does a neuron die?” he wondered. After poring over scientific studies, he sketched out his ideas for a way to treat them. “I was sitting in my dorm room and I had kind of written out the research on these crazy-looking diagrams,” he recalled. A study published on Wednesday in the New England Journal of Medicine reported that the experimental treatment he and another Brown student, Justin Klee, conceived might hold promise for slowing progression of amyotrophic lateral sclerosis, the ruthless disease that robs people of their ability to move, speak, eat and ultimately breathe. More than 50 clinical trials over 25 years have failed to find effective treatments for A.L.S., also called Lou Gehrig’s disease, which often causes death within two to five years. But now, scientific advances and an influx of funding are driving clinical trials for many potential therapies, generating hope and intense discussion among patients, doctors and researchers. The new study reported that a two-drug combination slowed progression of A.L.S. paralysis by about six weeks over about six months, approximately 25 percent more than a placebo. On average, patients on a placebo declined in 18 weeks to a level that patients receiving the treatment didn’t reach until 24 weeks, said the principal investigator, Dr. Sabrina Paganoni, a neuromuscular medicine specialist at Massachusetts General Hospital’s Healey & AMG Center for A.L.S. “It’s such a terrible disease and as you can imagine, for the folks who have it or the family members, it’s just desperation that something’s going to work,” said Dr. Walter Koroshetz, director of the National Institute of Neurological Disorders and Stroke, who wasn’t involved in the new study. “Any kind of slowing of progression for a patient with A.L.S. might be valuable even though it’s not a big effect.” © 2020 The New York Times Company

Related chapters from BN: Chapter 11: Motor Control and Plasticity
Related chapters from MM:Chapter 5: The Sensorimotor System
Link ID: 27455 - Posted: 09.05.2020

Laura P.W. Ranum An FDA-approved diabetes drug shows early signs of promise against the most common genetic form of amyotrophic lateral sclerosis, a devastating neurological condition that causes paralysis. ALS is a progressive disease that affects neurons in the brain and spinal cord. Motor neurons transmit signals from our brain to our muscles and allow us to move. ALS causes these motor neurons to die, resulting in the loss of a patient’s ability to speak, eat, move and breathe. Notable ALS patients include New York Yankees baseball star Lou Gehrig (the disease is often called Lou Gehrig’s disease), physicist Stephen Hawking and New Orleans Saints football star Steve Gleason. There are currently more than 30,000 cases of ALS in the United States, and life expectancy after diagnosis is typically 2 to 5 years. There is currently no cure for ALS. I am a scientist who studies neurological diseases that run in families, and I have been working hard to find a treatment to stop ALS. Our team has made a discovery, detailed in a scientific study, that paves the way for further research for improving disease in a genetic type of ALS caused by a mutation in a gene with the unwieldy name chromosome 9 open reading frame 72 (C9orf72), based on its location on chromosome 9. In addition to ALS, mutations in this gene can also cause frontotemporal dementia, which can cause apathy, loss of emotional control and cognitive decline. Some patients with the C9orf72 mutation develop ALS, others develop frontotemporal dementia and some develop both. Together, these diseases are referred to here as C9-ALS/FTD. I have been focusing on C9-ALS, which is the most common genetic type of ALS which is caused by a mutation in the C9orf72 gene. The mutation occurs when six letters of DNA that make up part of the gene’s genetic code – GGGGCC – are repeated hundreds of extra times. It is as if a single word is repeated hundreds of times in the same sentence. © 2010–2020, The Conversation US, Inc.

Related chapters from BN: Chapter 11: Motor Control and Plasticity; Chapter 13: Homeostasis: Active Regulation of the Internal Environment
Related chapters from MM:Chapter 5: The Sensorimotor System; Chapter 9: Homeostasis: Active Regulation of the Internal Environment
Link ID: 27379 - Posted: 07.21.2020

For every cell in the body there comes a time when it must decide what it wants to do for the rest of its life. In an article published in the journal PNAS, National Institutes of Health researchers report for the first time that ancient viral genes that were once considered “junk DNA” may play a role in this process. The article describes a series of preclinical experiments that showed how some human endogenous retrovirus (HERV-K) genes inscribed into chromosomes 12 and 19 may help control the differentiation, or maturation, of human stem cells into the trillions of neurons that are wired into our nervous systems. The experiments were performed by researchers in a lab led by Avindra Nath, M.D., clinical director, at the NIH’s National Institute of Neurological Disorders and Stroke (NINDS). Over the course of evolution, the human genome has absorbed thousands of human endogenous retrovirus genes. As a result, nearly eight percent of the DNA that lines our chromosomes includes remnants of these genes. Although once thought to be inactive, or “junk”, recent studies have shown that these genes may be involved in human embryonic development, the growth of some tumors, and nerve damage during multiple sclerosis. Previously, researchers in Dr. Nath’s lab showed that amyotrophic lateral sclerosis (ALS) may be linked to activation of the HERV-K gene. In this study, led by Tongguang (David) Wang, M.D., Ph.D., staff scientist at NINDS, the team showed that deactivation of the gene may free stem cells to become neurons. The researchers performed most of their experiments on blood cells, drawn from healthy volunteers at the NIH’s Clinical Center, that they genetically transformed into induced pluripotent stem cells, which can then turn into any cell type in the body. Surprisingly, they found that the surfaces of the stem cells were lined with high levels of HERV-K, subtype HML-2, an envelope protein, that viruses often use to latch onto and infect cells. These proteins progressively disappeared as the cells were served two rounds of “cocktails.” One round nudged the cells into an intermediate, neural stem cell state followed by a second round that pushed the cells into finally becoming neurons.

Related chapters from BN: 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 4: Development of the Brain
Link ID: 27359 - Posted: 07.14.2020

Jon Hamilton The same process that causes dew drops to form on a blade of grass appears to play an important role in Alzheimer's disease and other brain diseases. The process, known as phase transition, is what allows water vapor to condense into liquid water, or even freeze into solid ice. That same sort of process allows brain cells to constantly reorganize their inner machinery. But in degenerative diseases that include amyotrophic lateral sclerosis, frontotemporal dementia and Alzheimer's, the phase transitions inside neurons seem to go awry, says Dr. J. Paul Taylor, a neurogeneticist at St. Jude Children's Research Hospital in Memphis, and an investigator with the Howard Hughes Medical Institute. This malfunctioning prompts the interior of the cell to become too viscous, Taylor says. "It's as if you took a jar of honey [and] left it in the refrigerator overnight." In this sticky environment, structures that previously could nimbly disassemble and move around become "irreversibly glommed together," says Clifford Brangwynne, a professor of chemical and biological engineering at Princeton University and an investigator with the Howard Hughes Medical Institute. "And when they're irreversibly stuck like that, they can no longer leave to perform functions elsewhere in the cell." That glitch seems to allow toxins to begin to build up in and around these dysfunctional cells, Taylor says — including the toxins associated with Alzheimer's and other neurodegenerative diseases. The science behind this view of brain diseases has emerged only in the past decade. In 2009, Brangwynne was part of a team that published a study showing that phase transitions are important inside cells — or at least inside the reproductive cells of worms. © 2020 npr

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior; Chapter 11: Motor Control and Plasticity
Related chapters from MM:Chapter 4: Development of the Brain; Chapter 5: The Sensorimotor System
Link ID: 27351 - Posted: 07.08.2020