ALS Archives - Amazing Health Advances

Promising New Drug Could Slow Progression of ALS

The AHA! Team — Mon, 25 Nov 2024 06:46:21 +0000

John Jeffay via Israel21c – A chance encounter with an inspiring ALS patient, prompted Alon Ben-Noon to set up NeuroSense Therapeutics, a startup developing a drug combo that aims to slow progression of ALS and other neurodegenerative diseases. It was a life-changing moment for Alon Ben-Noon when he first met Shay Rishoni. Rishoni, once a keen runner and cyclist, had been robbed of all movement by the devastating and degenerative disease ALS. It was 2016 and Rishoni was by then immobile, only able to communicate by staring at an eye-tracking computer screen. But that didn’t stop him working as CEO of Prize4Life, a nonprofit founded by other ALS patients to help find a treatment for the disease. Ben-Noon was profoundly moved by the meeting. “I looked at myself and I thought: You’re completely functioning, but you’re not doing half of what he’s doing. He’s completely paralyzed and he’s moving mountains.” Ben-Noon was already working in the pharmaceutical industry, as a consultant, but decided to change track and do everything he could to allow ALS patients to live longer and live better. And so NeuroSense Therapeutics was born. The pharmaceutical startup, based in Herzliya, central Israel, aims to slow the progress of ALS (amyotrophic lateral sclerosis) as well as Alzheimer’s and Parkinson’s, which are also neurodegenerative disorders. PrimeC ALS is a rare and incurable disease caused by the death of motor neurons, the nerve cells that send messages from the brain and spinal cord to our muscles and glands. ALS (also known as Lou Gehrig’s disease) leads to complete paralysis, followed by death, usually with two to five years. Rishoni, married with two sons, was diagnosed when he was 45 and survived another seven years, which is longer than most. At the time, the only medication available was a drug called Riluzole, approved for use in 1995, which extended patients’ lives by around three months. Ben-Noon was determined to do better. He gathered a team of experts to identify molecules in existing drugs that could be combined to attack multiple targets associated with ALS. Previous attempts to treat the disease had focused on single targets. The team succeeded in addressing a number of distinct problems, including the degeneration of motor neurons. In clinical trials in Israel, Canada and Italy, the drug that NeuroSense developed has been shown to give ALS patients, on average, an extra 18 months. Patients experienced a 36% slower disease progression and a 43% better survival rate over 12 months compared to control subjects. The drug is named PrimeC – “prime” is English for “Rishoni” — and could be available for patients within three and a half years. The patented drug combines the antibiotic ciprofloxacin and the anti-inflammatory agent celecoxib, both already approved by the US Food and Drug Administration (FDA) for unrelated conditions. Fast progression ALS is a highly aggressive and complex disease that affects around one in 10,000 people. Initial symptoms are mild, such a weakness in a finger, or dragging a leg, but it can progress at an alarming rate. “Quality of life in terms of functionality is usually quite good at the beginning and then it declines as the disease progresses,” says Ben-Noon. “One day a patient can still eat by himself; the next day they’ll need assistance. One day a patient can walk independently and the next day they’ll have difficulties walking without a cane and soon they’ll need a wheelchair. “We understood quite quickly that we cannot reverse the disease, but we can stop it and make a meaningful change to people’s lives.” But he hopes to do even more. “Eventually, we will create a world where ALS is a non-fatal disease. Patients will live life to the full, happily, maybe with a very small dysfunction. That’s it, that’s the vision,” Ben-Noon says. Orphan drug designation NeuroSense has received orphan drug designation in the US and Europe, recognizing its potential to treat a rare condition (which means tax breaks and other benefits for the company) though it still needs to gain regulatory approval pending further clinical trials. The company, which went public on NASDAQ in December 2021, has so far attracted $30 million in funding and has a US office in Cambridge, Massachusetts. “We are only 16 employees but we work with dozens of consultants and vendors who are assisting us in advancing our programs,” says Ben-Noon. Dr. Vivian Drory, director of the ALS clinic at Tel Aviv Sourasky Medical Center, said that promising results from the company’s 12-month clinical study highlight the significant potential of PrimeC as a disease-modifying drug for ALS. “These findings underscore the importance of early intervention, which can lead to more substantial benefits, and provide valuable insights that will inform the design of the company’s Phase 3 study, increasing the likelihood of success,” she said. It’s often small companies, like NeuroSense, that pioneer new drugs, Ben-Noon notes. “Nowadays the ratio is about 60/40 — 60 for the small companies 40 for big pharma,” says Ben-Noon. “In many cases it starts in a very small company like ours and then a big pharma looks at the outcomes and decides to buy out the company and continue the development.” Looking back to his first meeting with Rishoni, back in 2016, does he feel he’s done what he set out to achieve? “Yes, absolutely,” he says. “We always keep in touch with Tami [Rishoni’s widow]. We talk, we meet and every time we reach a new milestone is very fulfilling.” “If I hadn’t bumped into Shay,” he reflects, “I probably would still be doing medical consulting work. But now I’m very proud to say we’re creating change in the world.” For more information, click here. To read the original article click here.

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New Brain-Computer Interface Allows Man with ALS to ‘Speak’ Again

The AHA! Team — Fri, 11 Oct 2024 08:20:41 +0000

UC Davis Health via Newswise – Technology developed by UC Davis Health restores interpersonal communication A new brain-computer interface (BCI) developed at UC Davis Health translates brain signals into speech with up to 97% accuracy — the most accurate system of its kind. The researchers implanted sensors in the brain of a man with severely impaired speech due to amyotrophic lateral sclerosis (ALS). The man was able to communicate his intended speech within minutes of activating the system. A study about this work was published today in the New England Journal of Medicine. ALS, also known as Lou Gehrig’s disease, affects the nerve cells that control movement throughout the body. The disease leads to a gradual loss of the ability to stand, walk and use one’s hands. It can also cause a person to lose control of the muscles used to speak, leading to a loss of understandable speech. The new technology is being developed to restore communication for people who can’t speak due to paralysis or neurological conditions like ALS. It can interpret brain signals when the user tries to speak and turns them into text that is ‘spoken’ aloud by the computer. “Our BCI technology helped a man with paralysis to communicate with friends, families and caregivers,” said UC Davis neurosurgeon David Brandman. “Our paper demonstrates the most accurate speech neuroprosthesis (device) ever reported.” Brandman is the co-principal investigator and co-senior author of this study. He is an assistant professor in the UC Davis Department of Neurological Surgery and co-director of the UC Davis Neuroprosthetics Lab. The new BCI breaks the communication barrier When someone tries to speak, the new BCI device transforms their brain activity into text on a computer screen. The computer can then read the text out loud. To develop the system, the team enrolled Casey Harrell, a 45-year-old man with ALS, in the BrainGate clinical trial. At the time of his enrollment, Harrell had weakness in his arms and legs (tetraparesis). His speech was very hard to understand (dysarthria) and required others to help interpret for him. In July 2023, Brandman implanted the investigational BCI device. He placed four microelectrode arrays into the left precentral gyrus, a brain region responsible for coordinating speech. The arrays are designed to record the brain activity from 256 cortical electrodes. “We’re really detecting their attempt to move their muscles and talk,” explained neuroscientist Sergey Stavisky. Stavisky is an assistant professor in the Department of Neurological Surgery. He is the co-director of the UC Davis Neuroprosthetics Lab and co-principal investigator of the study. “We are recording from the part of the brain that’s trying to send these commands to the muscles. And we are basically listening into that, and we’re translating those patterns of brain activity into a phoneme — like a syllable or the unit of speech — and then the words they’re trying to say.” Faster training, better results Despite recent advances in BCI technology, efforts to enable communication have been slow and prone to errors. This is because the machine-learning programs that interpreted brain signals required a large amount of time and data to perform. “Previous speech BCI systems had frequent word errors. This made it difficult for the user to be understood consistently and was a barrier to communication,” Brandman explained. “Our objective was to develop a system that empowered someone to be understood whenever they wanted to speak.” Harrell used the system in both prompted and spontaneous conversational settings. In both cases, speech decoding happened in real time, with continuous system updates to keep it working accurately. The decoded words were shown on a screen. Amazingly, they were read aloud in a voice that sounded like Harrell’s before he had ALS. The voice was composed using software trained with existing audio samples of his pre-ALS voice. At the first speech data training session, the system took 30 minutes to achieve 99.6% word accuracy with a 50-word vocabulary. “The first time we tried the system, he cried with joy as the words he was trying to say correctly appeared on-screen. We all did,” Stavisky said. In the second session, the size of the potential vocabulary increased to 125,000 words. With just an additional 1.4 hours of training data, the BCI achieved a 90.2% word accuracy with this greatly expanded vocabulary. After continued data collection, the BCI has maintained 97.5% accuracy. “At this point, we can decode what Casey is trying to say correctly about 97% of the time, which is better than many commercially available smartphone applications that try to interpret a person’s voice,” Brandman said. “This technology is transformative because it provides hope for people who want to speak but can’t. I hope that technology like this speech BCI will help future patients speak with their family and friends.” The study reports on 84 data collection sessions over 32 weeks. In total, Harrell used the speech BCI in self-paced conversations for over 248 hours to communicate in person and over video chat. “Not being able to communicate is so frustrating and demoralizing. It is like you are trapped,” Harrell said. “Something like this technology will help people back into life and society.” “It has been immensely rewarding to see Casey regain his ability to speak with his family and friends through this technology,” said the study’s lead author, Nicholas Card. Card is a postdoctoral scholar in the UC Davis Department of Neurological Surgery. “Casey and our other BrainGate participants are truly extraordinary. They deserve tremendous credit for joining these early clinical trials. They do this not because they’re hoping to gain any personal benefit, but to help us develop a system that will restore communication and mobility for other people with paralysis,” said co-author and BrainGate trial sponsor-investigator Leigh Hochberg. Hochberg is a neurologist and neuroscientist at Massachusetts General Hospital, Brown University and the VA Providence Healthcare System. Brandman is the site-responsible principal investigator of the BrainGate2 clinical trial. The trial is enrolling participants. To learn more about the study, visit braingate.org or contact braingate@ucdavis.edu. A complete list of coauthors and funders is available in the article. Caution: Investigational device. Limited by Federal law to investigational use. To read the original article click here.

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Targeting the Brain Should Be the Focus of ALS Therapy, Not Just Spinal Cord

AHA Publisher — Mon, 06 Dec 2021 08:00:40 +0000

Northwestern University via News-Medical – The brain is indeed a target for treating ALS (amyotrophic lateral sclerosis), Northwestern Medicine scientists have discovered. This flips a long-standing belief that the disease starts in the spinal motor neurons and any therapy would need to target the spine as the key focus. A new Northwestern study shows the degeneration of brain motor neurons (the nerve cells in the brain that control movement of the limbs) is not merely a byproduct of the spinal motor neuron degeneration, as had been previously thought. “We have discovered that the brain degenerates early in diseases like ALS, sends us warning signals and shows defects very early in the disease. Therefore, we need to repair the brain motor neurons if we want long-term and effective treatment strategies. The brain is important in ALS.” Hande Ozdinler, lead study author, associate professor of neurology, Northwestern University Feinberg School of Medicine The paper will be published Dec. 2 in Gene Therapy. ALS is a swift and fatal neurodegenerative disease that paralyzes its victims. Upper motor neuron diseases, such as ALS, hereditary spastic paraplegia and primary lateral sclerosis affect more than 250,000 people a year in the U.S. alone. There is no cure and no effective long-term treatment strategy. This is the first study to clearly reveal the brain motor neuron degeneration is not a consequence of spinal motor neuron degeneration but is independent of the spinal motor neuron degeneration. The research also is the first to show that the gene UCHL1 is important for maintaining the health of brain motor neurons that are diseased due to two independent underlying causes. One is the accumulation of badly folded proteins and the other is the accumulation of sticky protein clumps inside the cells. These problems are observed in more than 90% of all ALS cases and also in other cases of upper motor neuron diseases. “Our findings not only give legitimacy for targeting brain motor neuron health in ALS as a therapeutic intervention, it also reveals the first target gene that can help these neurons be revitalized,” Ozdinler said. “This has huge clinical implications,” Ozdinler said. “Being able to modulate gene expression in diseased brain motor neurons in upper motor neuron disease patients is mind boggling. Since movement starts in the brain, if we can make the brain motor neurons happy and healthy, if we can boost their health and integrity with directed gene delivery, we may begin to develop personalized treatment options especially for patients with upper motor neuron disease, who currently have no effective treatment options. Northwestern University scientists have previously identified NU-9, the first compound that eliminates the ongoing degeneration of upper motor neurons that become diseased and are a key contributor to ALS. Now, this study reveals the importance and significance of treating upper motor neurons in ALS and identifies the first genetic target. The next step is to determine the best dose and the best site of injection with respect to improvement of movement and reduction of disease conditions in at least two different ALS disease models. After preclinical toxicology studies, scientists will move to translate these results into a clinical trial, a process that likely will take several years. To read the original article click here.

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Potential ALS Drug Gets Boost Toward Preclinical Trials

AHA Publisher — Fri, 05 Nov 2021 07:00:58 +0000

Abigail Klein Leichman via Israel21c – A new class of small molecules for treating amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s Disease, and other neurodegenerative diseases, is being developed at Neuromagen Pharma of Beersheva with several million dollars in seed money raised from local private investors. “Currently there are no drugs available to treat ALS, so our drug candidate presents a new treatment paradigm and could be both first and best-in-class,” said Dr. Gil Ben-Menachem, founder and chief executive officer of Neuromagen. The preclinical-stage company – whose name means “neuro shield” in Hebrew — was incubated at the Ben-Gurion University of the Negev (BGU) Oazis accelerator and venture builder. It grew out of research conducted by BGU Prof. Esther Priel and her team at the university’s Laboratory for Nucleic Acids Topology. She is the company’s cofounder and chief scientific officer. Priel and her team have published papers describing how the family of novel small molecules they developed activates the transcription of a major surviving enzyme, telomerase reverse transcriptase, which protects and rehabilitates neuronal cells. When tested in ALS animal models, these drug candidates demonstrated delayed onset as well as delayed progression of the disease, and increased survival of the neurons by 60 percent. Neuromagen Pharma’s drug is not expected to be a cure; the goal is to delay the onset and progression of neurodegenerative diseases, thereby improving the quality and length of life for individuals with such diseases. Ben-Menachem said the funding “will enable us to jumpstart the company and initiate the preclinical work towards developing our promising drug candidates.” This work is a step that is necessary before proceeding to human clinical trials for regulatory approval. In December, the company will present its findings at the virtual 32nd International Symposium on ALS/MND. To read the original article click here.

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URI Engineering Professor Helping ALS Patients Use Their Brains to Communicate

AHA Publisher — Wed, 01 Jul 2020 07:00:20 +0000

University of Rhode Island via Newswise – Doug Sawyer was diagnosed with amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, 11 years ago. His only muscles that still function are those that control eye movement. Despite his disability, Sawyer still works as an engineer from his home, designing electronics for Hayward Industries. Using only his eyes, the 57-year-old writes reports and other papers, draws pictures and schematics, talks on the phone, sends text messages and emails, and attends meetings online multiple times a week. However, Sawyer’s gaze weakens as he gets tired, causing the technology he currently uses to become ineffective. That’s why the Seekonk, Massachusetts resident was eager to work with University of Rhode Island Assistant Professor Yalda Shahriari to develop a new way for ALS patients to communicate. Shahriari and her team of student researchers in URI’s College of Engineering are developing a way for those with severe motor deficits such as ALS to communicate using brain signals, eliminating the need for patients to maintain fine eye-gaze control. Her project, funded by a National Science Foundation (NSF) grant, has two main goals. The first is to develop multimodal personalized algorithms to improve the robustness of the brain-computer interface (BCI) systems for patients with severe motor deficits. The second is to develop an autonomous hybrid system for non-communicative patients who are without residual motor control, such as those who lose their fine eye-gaze control in the late stages of ALS. Through longitudinal recordings taken of several patients with ALS during this and previous projects, Shahriari and her group have noticed significant day-to-day variations in brain-computer interface performance. “These variations are speculated to be associated with several factors, including cognitive fluctuations and environmental factors,” said Shahriari. “Developing personalized algorithms will enable us to predict these fluctuations and optimize performance based on each patient’s specifications and needs.” To ensure more accurate readings of brain activity, two non-invasive techniques are implemented simultaneously: electroencephalogram (EEG) and functional Near Infrared Spectroscopy (fNIRS) signals. EEG detects electrical activity in the brain using small, metal discs called electrodes. Functional Near Infrared Spectroscopy is an optical imaging technique in which an emitter transmits near infrared light and a detector detects the light reflected from the surface of the brain. This technique measures oxygen changes in the concentration of hemoglobin in the brain. The higher the concentration, the more activity is taking place. “We will use a hybrid of EEG and fNIRS signals to compensate for each neuroimaging modality shortage and use the complementary features obtained from each modality to improve our system,” said Shahriari. For patients in the later stages of ALS who experience cognitive dysfunction, such as memory loss and the inability to maintain eye gaze on objects, Functional Near Infrared Spectroscopy has shown to be a more accurate method of measurement. Shahriari and her students have developed a visuo-mental dual task paradigm which relies on conventional oddball-based protocols, but require the subjects to do some mental arithmetic tasks. This BCI approach is accomplished by displaying a grid of letters and numbers and intermittently flashing an image (matrix of digits) over each row and column. “By giving the patient higher demanding tasks to focus on, we can trigger several cognitive functions and extract the associated signatures or neural biomarkers,” said doctoral student Bahram Borgheai. “The computer can then decode the pattern of neural activities that appear after the patient performs the tasks. The patterns can be used for diagnostic and communication purposes.” Shahriari has collaborated with the National Center for Adaptive Neurotechnologies on projects since 2012. With the support of the national center, the Rhode Island Chapter of the ALS Association and Rhode Island Hospital, the professor would like to add more patients to the study. “Our analysis of the data becomes much more powerful if we can significantly increase the number of patients in the study,” said Shahriari. Patients will be asked to wear a cap with sensors attached that can record brain activity in the comfort of their homes or at a care center. Recordings of those with healthy brains will take place in Shahriari’s Neural Processing and Control Laboratory in URI’s Fascitelli Center for Advanced Engineering. All data processing and analysis will be conducted in the lab. Once enough patients have volunteered to participate in the research project, Shahriari plans to partner with more local hospitals and medical schools to take advantage of their clinical expertise. Sawyer has relished the opportunity to participate in the study. “Taking part in the brain activity study has been very rewarding,” said Sawyer. “I enjoy learning new things and staying abreast of the latest technology. Dr. Shahriari and her team have been willing to share their progress. They make me feel as if I’m part of their team and not just a test number.” Sawyer hopes that his participation will help Shahriari develop a way for ALS patients to work and communicate after their motor functions have ceased. “I don’t consider myself a victim of ALS and I don’t consider myself handicapped,” Sawyer said. “I just need help sometimes. There are people out there far worse off than me. Hopefully the time I give to Dr. Shahriari will someday improve their lives.” To read the original article click here.

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Research Findings May One Day Help Keep ALS at Bay

AHA Publisher — Sun, 19 Jan 2020 08:00:47 +0000

Dr. Liji Thomas, MD via News-Medical – A new study published in the journal Nature Medicine on December 23, 2019, shows how to silence a defective gene responsible for the degeneration of the motor neurons in Lou Gehrig’s disease, or amyotrophic lateral sclerosis (ALS), in adult mice. This could help prevent disease progression if the condition is already symptomatic, and even suppress the illness if it has not yet started. The current study used a vector, or agent, capable of silencing a particular gene implicated in the motor neuron disease called ALS. The result of this therapy is to either arrest or prevent neuronal degeneration depending on whether the symptoms have already appeared, or it is given prior to disease onset. Amyotrophic Lateral Sclerosis A rare disease, ALS hits over 5000 Americans each year, and about 30,000 people in the US have this disease at present. ALS is a fatal condition caused by degeneration of the motor neurons in the spinal cord that connect the brain with the muscle cells responsible for voluntary action. Since these nerve cells no longer function, skeletal muscle cells that initiate movement of body parts, speaking, swallowing and breathing, are affected progressively by their lack of nerve supply. The only thing that can be done at present for these patients is symptomatic treatment. most patients live less than 2-5 years from the date of diagnosis. ALS can occur in a sporadic or familial form, the former being the most common form by far (90% to 95%). The 5% to 10% that are familial are inherited, due to the occurrence of one or more of over 200 mutations of the SOD1 gene. This gene is one that encodes the protein superoxide dismutase (SOD), an enzyme that breaks down toxic superoxide radicals that are generated during the cell’s normal metabolism. Earlier work indicates that when the SOD1 gene is mutated, superoxide radicals may not be removed efficiently, or other changes in superoxide metabolism may occur that lead to injury and death of motor neurons. The end result is ALS. The Study To counter this effect, the scientists introduced shRNA, which is a synthetic molecule engineered to silence the gene target or turn off its expression. This shRNA is delivered to the cell inside a harmless virus called AAV (adeno-associated virus). Earlier researchers had tried the effect of introducing the shRNA-carrying vector into the blood directly, or into the cerebrospinal fluid (CSF) that bathes the central nervous system. They found that the injections were capable of delaying the progress of the disease but not of stopping it altogether. In fact, the mice treated in this way died quite soon after this treatment was given. In the current study, the AAV vector containing the shRNA was injected at two places in the spinal cord of the adult experimental mice in which the ALS-associated gene defect was present. One group of mice did not yet have symptoms while the other group of animals had already begun to show signs of illness. The injection was given in the subpial space. The pia mater is the delicate film-like membrane that covers the surface of the brain, dipping into all its folds like a thin transparent plastic sheath. The Findings The results were amazing. A single injection into the subpial space reduced the level of nerve cell degeneration in the mice carrying the gene defect, before the onset of symptoms, causing them to appear and test normal with respect to neurological function. In fact, it appears that the injection resulted in almost 100% protection of the motor neuron cells and other related parts, such as the neuromuscular junctions. If the mice already had symptoms of neuron degeneration, the injection prevented further damage to the motor neuron cells and halted the progress of the condition. In both cases, therefore, the mice showed no adverse effects throughout the study period. Even at one year following treatment, the mice remain free of any discernible side effects. Making Sure The scientists repeated the same injection technique with the same vector in adult pigs, because their spinal cord size is remarkable like that of humans. They wanted to learn if the approach worked safely and effectively in these large mammals. The device they used was one adapted for human use. They found that indeed the technique was both reliable and uncomplicated. Implications and Future Directions Researcher Martin Marsala says, “At present, this therapeutic approach provides the most potent therapy ever demonstrated in mouse models of mutated SOD1 gene-linked ALS.” The researchers will now try to validate the effectiveness and safety of the treatment using large experimental animals, and to establish the dose required for its optimal and safe effect. They hope to confirm the safety of the technique in large animal models that are more like humans in their physiology, since this is essential to conducting a clinical trial of this approach in the future. The scientists say that the fact that the new treatment can be given by subpial injection of the silencing shRNA within the AAV9 vector into the spinal cord makes it an attractive option for other hereditary types of ALS and other diseases due to spinal degeneration, like C9orf72 mutation-linked ALS, or in certain lysosomal storage diseases. This is because the therapeutic agent, whether a corrective gene or a gene-silencing cellular apparatus, can be given straight into the parenchyma of the spinal cord. To read the original article click here.

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Self-Cannibalizing Mitochondria May Set the stage for ALS Development

AHA Publisher — Wed, 13 Nov 2019 08:00:28 +0000

Northwestern University via EurekAlert – Powerhouses of the cell ‘eat themselves up,’ jumpstart path to neurodegenerative disease. CHICAGO — Northwestern Medicine scientists have discovered a new phenomenon in the brain that could explain the development of early stages of neurodegeneration that is seen in diseases such as ALS, which affects voluntary muscle movement such as walking and talking. The discovery was so novel, the scientists needed to coin a new term to describe it: mitoautophagy, a collection of self-destructive mitochondria in diseased upper motor neurons of the brain that begin to disintegrate from within at a very early age. Upper motor neurons in the brain are responsible for initiating muscle movement and relaxation and are one of the first to break down in neurodegenerative diseases. The study will be published on November 7 in the journal Frontiers in Cellular Neuroscience. The phenomenon is observed mainly in one of the most common pathologies observed in neurodegenerative diseases, TDP-43 pathology, which is seen in more than 90% of ALS cases. When a pathology is present in the body, it indicates that something is wrong or functioning abnormally. “I think we have found the culprit that primes neurons to become vulnerable to future degeneration: suicidal mitochondria,” said senior study author Hande Ozdinler, associate professor of neurology at Northwestern University Feinberg School of Medicine. “The mitochondria basically eat themselves up very early in the disease. This occurs selectively in the neurons that will soon degenerate in patient’s brains.” “This type of degeneration begins much earlier than previously thought,” said study lead author Mukesh Gautam, the A Long Swim (ALS) Ellen Blakeman fellow at Northwestern. Using a process called immuno-coupled electron microscopy, the scientists investigated the cellular events that go wrong inside the neurons that become vulnerable to disease. After analyzing more than 200 neurons, they observed the self-destruction of mitochondria only in the diseased neurons, and especially within the context of TDP-43 pathology. Mitochondria are powerhouses of the cell that create and maintain energy in the cells. In the diseased upper motor neurons, mitochondria self-destruct first by elongating, then forming a ring-like structure, until they finally disintegrate from the inside out. It is a type of degeneration never been seen before, and it is different from previously described stages of mitochondrial degeneration. The study analyzed mitochondria in the upper motor neurons of three different mouse models of ALS at only 15 days old – equivalent to a toddler in humans. While the study was in mice, Ozdinler and her team showed many times before that the upper neurons even in different species are almost identical at a cellular level, especially within the context of TDP-43 pathology. These self-destructive mitochondria could become a future target for drug therapies to treat ALS and other neurodegenerative diseases in which a person’s movement is affected, Ozdinler said. They are currently working with drug companies to see if drugs used for human patients with mitochondrial disease could in fact improve the health of diseased motor neurons. “Many of the drugs currently on the market that target the health and the integrity of mitochondria may well be repurposed and considered for neurodegenerative diseases in the future,” Ozdinler said. “Maybe we don’t need to reinvent the wheel to cure ALS and other neurodegenerative diseases. “To overcome neurodegeneration, we need to improve the health and the stability of mitochondria. If we improve the health of the mitochondria early, we may even eliminate protein aggregate formation, a pathology broadly observed in many diseases.” To read the original article click here.

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