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Tag: Paralysis

  • Stem cell therapy safe and potentially beneficial for spinal cord injury patients

    Stem cell therapy safe and potentially beneficial for spinal cord injury patients

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    A Mayo Clinic study shows stem cells derived from patients’ own fat are safe and may improve sensation and movement after traumatic spinal cord injuries. The findings from the phase 1 clinical trial appear in Nature Communications. The results of this early research offer insights on the potential of cell therapy for people living with spinal cord injuries and paralysis for whom options to improve function are extremely limited.

    In the study of 10 adults, the research team noted seven participants demonstrated improvements based on the American Spinal Injury Association (ASIA) Impairment Scale. Improvements included increased sensation when tested with pinprick and light touch, increased strength in muscle motor groups, and recovery of voluntary anal contraction, which aids in bowel function. The scale has five levels, ranging from complete loss of function to normal function. The seven participants who improved each moved up at least one level on the ASIA scale. Three patients in the study had no response, meaning they did not improve but did not get worse.

    This study documents the safety and potential benefit of stem cells and regenerative medicine. Spinal cord injury is a complex condition. Future research may show whether stem cells in combination with other therapies could be part of a new paradigm of treatment to improve outcomes for patients.”


    Mohamad Bydon, M.D., a Mayo Clinic neurosurgeon and first author of the study

    No serious adverse events were reported after stem cell treatment. The most commonly reported side effects were headache and musculoskeletal pain that resolved with over-the-counter treatment.

    In addition to evaluating safety, this phase 1 clinical trial had a secondary outcome of assessing changes in motor and sensory function. The authors note that motor and sensory results are to be interpreted with caution given limits of phase 1 trials. Additional research is underway among a larger group of participants to further assess risks and benefits.

    The full data on the 10 patients follows a 2019 case report that highlighted the experience of the first study participant who demonstrated significant improvement in motor and sensory function.

    Stem cells’ mechanism of action not fully understood

    In the multidisciplinary clinical trial, participants had spinal cord injuries from motor vehicle accidents, falls and other causes. Six had neck injuries; four had back injuries. Participants ranged in age from 18 to 65.

    Participants’ stem cells were collected by taking a small amount of fat from a 1- to 2-inch incision in the abdomen or thigh. Over four weeks, the cells were expanded in the laboratory to 100 million cells and then injected into the patients’ lumbar spine in the lower back. Over two years, each study participant was evaluated at Mayo Clinic 10 times.

    Although it is understood that stem cells move toward areas of inflammation -; in this case the location of the spinal cord injury -; the cells’ mechanism of interacting with the spinal cord is not fully understood, Dr. Bydon says. As part of the study, researchers analyzed changes in participants’ MRIs and cerebrospinal fluid as well as in responses to pain, pressure and other sensation. The investigators are looking for clues to identify injury processes at a cellular level and avenues for potential regeneration and healing.

    The spinal cord has limited ability to repair its cells or make new ones. Patients typically experience most of their recovery in the first six to 12 months after injuries occur. Improvement generally stops 12 to 24 months after injury. One unexpected outcome of the trial was that two patients with cervical spine injuries of the neck received stem cells 22 months after their injuries and improved one level on the ASIA scale after treatment.

    Two of three patients with complete injuries of the thoracic spine -; meaning they had no feeling or movement below their injury between the base of the neck and mid-back -; moved up two ASIA levels after treatment. Each regained some sensation and some control of movement below the level of injury. Based on researchers’ understanding of traumatic thoracic spinal cord injury, only 5% of people with a complete injury would be expected to regain any feeling or movement.

    “In spinal cord injury, even a mild improvement can make a significant difference in that patient’s quality of life,” Dr. Bydon says.

    Research continues into stem cells for spinal cord injuries

    Stem cells are used mainly in research in the U.S., and fat-derived stem cell treatment for spinal cord injury is considered experimental by the Food and Drug Administration.

    Between 250,000 and 500,000 people worldwide suffer a spinal cord injury each year, according to the World Health Organization.

    An important next step is assessing the effectiveness of stem cell therapies and subsets of patients who would most benefit, Dr. Bydon says. Research is continuing with a larger, controlled trial that randomly assigns patients to receive either the stem cell treatment or a placebo without stem cells.

    “For years, treatment of spinal cord injury has been limited to supportive care, more specifically stabilization surgery and physical therapy,” Dr. Bydon says. “Many historical textbooks state that this condition does not improve. In recent years, we have seen findings from the medical and scientific community that challenge prior assumptions. This research is a step forward toward the ultimate goal of improving treatments for patients.”

    Dr. Bydon is the Charles B. and Ann L. Johnson Professor of Neurosurgery. This research was made possible with support from Leonard A. Lauder, C and A Johnson Family Foundation, The Park Foundation, Sanger Family Foundation, Eileen R.B. and Steve D. Scheel, Schultz Family Foundation, and other generous Mayo Clinic benefactors. The research is funded in part by a Mayo Clinic Transform the Practice grant.

    Source:

    Journal reference:

    Bydon, M., et al. (2024). Intrathecal delivery of adipose-derived mesenchymal stem cells in traumatic spinal cord injury: Phase I trial. Nature Communications. doi.org/10.1038/s41467-024-46259-y.

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  • Neural cell culture model sheds light on the intricate mechanisms underlying neurodegeneration

    Neural cell culture model sheds light on the intricate mechanisms underlying neurodegeneration

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    Scientists at the University of Zurich have developed an innovative neural cell culture model, shedding light on the intricate mechanisms underlying neurodegeneration. Their research pinpointed a misbehaving protein as a promising therapeutic target in the treatment of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).

    Neurodegenerative diseases cause some of the neurons in our brains to die, resulting in different symptoms depending on the brain region affected. In amyotrophic lateral sclerosis (ALS), neurons in the motor cortex and spinal cord degenerate, leading to paralysis. In frontotemporal dementia (FTD), on the other hand, neurons located in the parts of the brain involved in cognition, language and personality are affected.

    Both ALS and FTD are relentlessly progressive diseases and effective treatments are still lacking. As the population ages, the prevalence of age-related neurodegenerative diseases such as ALS and FTD is expected to increase.

    Despite the identification of the aberrant accumulation of a protein called TDP-43 in neurons in the central nervous system as a common factor in the vast majority of ALS and about half of FTD patients, the underlying cellular mechanisms driving neurodegeneration remain largely unknown.

    Flexible, durable, reproducible: ideal cell culture model for ALS and FTD research

    In their study, first author Marian Hruska-Plochan and corresponding author Magdalini Polymenidou of the Department of Quantitative Biomedicine at the University of Zurich developed a novel neural cell culture model that replicates the aberrant behavior of TDP-43 in neurons. Using this model, they discovered a toxic increase in the protein NPTX2, suggesting it as a potential therapeutic target for ALS and FTD.

    To mimic neurodegeneration, Marian Hruska-Plochan developed a new cell culture model called “iNets,” derived from human induced pluripotent stem cells. These cells, originated from skin cells and reprogrammed to a very early, undifferentiated stage in the laboratory, serve as a source for developing many different, desired cell types. iNets are a network of interconnected neurons and their supporting cells growing in multiple layers in a dish.

    The cultures lasted exceptionally long – up to a year – and were easily reproduced. +

    The robustness of aging iNets allows us to perform experiments that would not have been possible otherwise. And the flexibility of the model makes it suitable for a wide range of experimental methodologies.”


    Marian Hruska-Plochan, First Author

    As a case in point, the iNets cell cultures provided the ideal model to investigate the progression from TDP-43 dysfunction to neurodegeneration.

    How protein dysfunction leads to neurodegeneration

    Employing the iNets model, the researchers identified a toxic accumulation of NPTX2, a protein normally secreted by neurons through synapses, as the missing link between TDP-43 misbehavior and neuronal death. To validate their hypothesis, they examined brain tissue from deceased ALS and FTD patients and indeed found that, also in patients, NPTX2 accumulated in cells containing abnormal TDP-43. This means that the iNets culture model accurately predicted ALS and FTD patient pathology.

    In additional experiments in the iNets model, the researchers tested whether NPTX2 could be a target for drug design to treat ALS and FTD. The team engineered a setup in which they lowered the levels of NPTX2 while neurons were suffering from TDP-43 misbehavior. They found that keeping NPTX2 levels low counteracted neurodegeneration in the iNets neurons. Therefore, drugs that reduce the amount of the protein NPTX2 have potential as a therapeutic strategy to halt neurodegeneration in ALS and FTD patients.

    Magdalini Polymenidou sees great promise in this discovery: “We still have a long way to go before we can bring this to the patients, but the discovery of NPTX2 gives us a clear shot of developing a therapeutic that acts at the core of the disease,” she said. “In conjunction with two additional targets recently identified by other research teams, it is conceivable that anti-NPTX2 agents could emerge as a key component of combination therapies for ALS and FTD in the future,” she added.

    Source:

    Journal reference:

    Hruska-Plochan, M., et al. (2024). A model of human neural networks reveals NPTX2 pathology in ALS and FTLD. Nature. doi.org/10.1038/s41586-024-07042-7.

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  • ASU professor offers insights on what may be coming from Neuralink’s PRIME study

    ASU professor offers insights on what may be coming from Neuralink’s PRIME study

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    This week, Neuralink’s Elon Musk announced that human clinical trials have begun on its Precise Robotically Implanted Brain-Computer Interface (PRIME) study, a medical device trail that uses wireless, brain-computer interface designed to enable people with paralysis to control external devices with their thoughts.

    According to Arizona State University’s Bradley Greger, an associate professor of neural engineering who first addressed the plausibility of Neuralink’s technology in late 2022, “This technology is going to be such a gamechanger.”

    Greger has worked on restoring vision and speech using brain-computer interfaces, and is currently investigating how deep brain stimulation (DBS) treats patients with movement and pain disorders.

    “We are using DBS technology to record signals from the human brain, but we only have several channels,” said Greger. “Neuralink is using different technology to record from what is equivalent to thousands of channels.”

    As a neural engineer, Professor Greger offers his insights on what may be coming from Neuralink’s PRIME study. 

    Question: How accessible will this technology be to other researchers?

    Answer: That’s going to be up to Neuralink. Every researcher I’ve ever talked with about Neuralink has asked the same question: “When are we going to be able to get our hands on it?” 

    Q: Is Neuralink currently partnering with a research hospital?

    A: They definitely have partnered with a major neuro-surgical center somewhere in America with this first patient study. Nobody knows which one – they don’t want media hounding the hospital, the family and most importantly, the patient.

    Q: Do you think Neuralink will soon partner with additional neurological research institutions?

    A: Oh, absolutely – with multiple medical centers. I suspect that conversations and visits have been underway for a while. But potential partners are totally locked down by nondisclosure agreements as a precursor to research relationships.

    The criteria for partnership will be finding qualifying patients, but also institutions with the surgical skill and support infrastructure. There are not a lot of places that meet that criteria.

    If I were making the rounds for Neuralink, I’d be talking to the folks at Stanford, UC San Francisco and Massachusetts General – the places that have the neurosurgical expertise and have a proven track record of performing well in this type of research.

    Q: Will each of the partnering institutions have to go through the FDA approval process?

    A: Probably not. The technology and procedures are already FDA approved. The partners will go through an institutional review board (IRB) process at their institutions – every major hospital has its own IRB. 

    Q: Will the initial study focus exclusively on paralysis patients?

    A: Yes. I think the research partnerships they will take on first will focus on restoring movement for those with paralysis – patients that have amyotrophic lateral sclerosis (ALS) or severe spinal cord lesions.

    Control of movement is one of the things we understand most about the brain, so I’d say it’s the easiest target to begin with.

    I haven’t seen the actual protocol, but for this type of study you would typically want to work with about 10 or so patients.

    Q: How long do you think it will be before they expand the trial?

    A: This phase of the study will probably go about a year or two.

    If it all goes well and the devices are working as anticipated, and the patients are healthy beyond their paralysis issues, Neuralink may then move beyond feasibility trials into testing safety and efficacy. For instance, they might have a patients try to control robotic arms with their minds. With Neuralink’s technology, I think you could see that as soon as one year from now, or at the outside, two or three years.

    In the approval process for the FDA, they have to specify the type of patients they will work with.

    Q: If and when Neuralink moves beyond paralysis studies, will they have to go through the FDA approval process again for a speech restoration study?

    A: They will certainly need additional IRB approvals. FDA approvals revolve around the device. If they move to a speech restoration study, for example, researchers may have to get an investigational device exemption (IDE), but that’s much more simple process than establishing the safety of the device itself.

    For a vision restoration trial, they likely will have to go back to the FDA for another approval because that involves stimulation of the brain, which is quite different than this study. They probably have been working on a vision protocol in the background for years. 

    Although vision restoration will use the same technology, the same wiring and the same device, it will be implanted in in a different location and will involve electricity going into the brain rather than out of the brain. That’s what may make it different from the FDA’s perspective.

    Q: How long do you think it will take before Neuralink’s technology is actually available to the general public?

    A: The technology may be generally available with a physician’s or surgeon’s prescription in several years. Therefore, most initial users will be patients with neurological disorders. I am somewhat skeptical that healthy people will undergo neurosurgery to get the device or that the surgery would be allowed without some medical condition to be treated by the device.

    Source:

    Arizona State University (ASU)

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