The Seventy Ways That Actually Autistic People Stim
Multiple Sclerosis, Nutrition and Supplements
Dr. Conor Kerley is a dietician and nutrition researcher in Ireland. He was diagnosed with MS as a teenager, and has dedicated his career to studying diet and supplements and how they affect human health. We discuss some of the scientific evidence behind nutrition and various supplements and his recommendations.
“Researchers have identified a surprising mechanism behind kidney damage in lupus patients.”
Immunofluorescent images of kidney tissue show inflammation in green. The kidney tissue shown on the right was treated with an NKp46 receptor-blocking antibody, resulting in significantly reduced inflammation. Credit Charité
A team led by Charité – Universitätsmedizin Berlin, the German Rheumatology Research Center, and the Max Delbrück Center has identified key cells responsible for severe kidney damage in lupus. The research, which was published in “Nature,” can provide valuable insights for future antibody therapies.
A research team in Berlin has discovered key regulators of severe kidney damage in patients with lupus, an autoimmune disorder that affects an estimated five million people worldwide, most of whom are young women. They found that a small, specialized population of immune cells known as innate lymphoid cells (ILCs) triggers a cascade of effects that lead to harmful kidney inflammation, also known as lupus nephritis.
The research published this week in “Nature” challenges the traditional belief that autoantibodies, which are proteins produced by immune cells and mistakenly attack healthy tissues, are the primary cause of lupus nephritis.
“Autoantibodies alone are not enough to cause tissue damage. Our research shows that ILCs (innate lymphoid cells) play a crucial role in amplifying the damage to organs,” explained Dr. Masatoshi Kanda, a senior author of the study. Dr. Kanda was a Humboldt Fellow at Max Delbrück Center and is currently based at the Department of Rheumatology and Clinical Immunology at Sapporo Medical University in Japan.
Lupus, also known as systemic lupus erythematosus, is typically diagnosed between the ages of 15 and 45. The symptoms can vary in severity from mild to severe. However, the reason behind kidney damage in certain patients, to the extent of needing dialysis, has remained unclear.
“We have now identified most of the circuit controlled by ILCs in lupus nephritis by examining the entire kidney at single-cell resolution,” says Professor Antigoni Triantafyllopoulou of the German Rheumatology Research Center.
Unusual immune cells
ILCs are a small group of immune cells that live in a specific tissue or organ, unlike most other immune cells that circulate throughout the body.
“They are present in the tissues all the time, starting from the embryonic development stage, which sets them apart from other immune cells,” stated Professor Andreas Diefenbach, a senior author of the paper and the director of the Institute of Microbiology, Infectious Diseases, and Immunology at Charité – Universitätsmedizin Berlin.
Diefenbach’s laboratory was one of the first to discover ILCs in the mid-2000s. Most of his research is focused on ILCs in the gut and their effects on tissue function. In this study, Triantafyllopoulou and Kanda collaborated with Diefenbach’s group and Dr. Mir-Farzin Mashreghi at the DRFZ to investigate the presence of ILCs in the kidney and their potential role in lupus nephritis.
The whole single-cell picture
To unravel this mystery, the team utilized single-cell RNA sequencing, which identifies active genes in individual cells, helping researchers understand the cells’ identity and function.
Kanda, a rheumatologist who was studying bioinformatics in Professor Norbert Hübner’s lab at the Max Delbrück Center at the time, developed a specialized protocol for single-cell RNA sequencing of mouse and human kidneys. “Masatoshi’s protocol was very good at pulling out and preserving multiple types of kidney cells, which gave us a much more complete overview of how lupus affects the whole kidney,” explains Triantafyllopoulou. The team sequenced nearly 100,000 individual kidney and immune cells of various types and functions.
The key receptor
The research team found that a specific group of ILCs, which have a receptor called NKp46, play a key role in causing lupus nephritis in mice. When NKp46 is activated, these cells increase their production of a protein called GM-CSF, which in turn stimulates invading macrophages to multiply. Macrophages are large immune cells that consume dying cells and microbes. In the kidney, the influx of macrophages leads to severe tissue damage and the accumulation of scar tissue, known as fibrosis.
“These ILCs are really amplifiers in this system,” Diefenbach says. “They are small in population, but they seem to fertilize the whole process.”
When the team blocked NKp46 with antibodies or genetically removed the receptor, kidney tissue damage was minimal. They also blocked GM-CSF, which had similar anti-inflammatory effects.
“Critically, autoantibody levels did not change when NKp46 was inhibited, but kidney tissue damage was reduced, which shows autoantibodies are not directly responsible for kidney inflammation,” Triantafyllopoulou explains.
The research team also compared the results to sequencing data from tissue taken from human patients with lupus. They found that ILCs were present, but they stated that more work is needed to fully understand how to target ILCs in human kidneys. However, the detailed studies provided new insights that suggest potential antibody therapies for patients with severe forms of lupus. The ultimate goal is to prevent the need for kidney dialysis in these patients.
“Feeling sleepy at the wheel? Not with these fatigue-detecting earbuds!”
UC Berkeley researchers have developed earpieces that detect brain activity associated with relaxation and drowsiness.
Ryan Kaveh/UC Berkeley
It’s important to remember the following text: “Many people experience sleepiness at work, particularly after a large meal. However, drowsiness can pose a serious danger for individuals in roles that involve driving or operating heavy machinery, potentially leading to fatal accidents. In the U.S., drowsy driving results in hundreds of deadly vehicle crashes each year, and the National Safety Council has identified drowsiness as a significant risk in the construction and mining industries.”
Engineers at the University of California, Berkeley, have developed prototype earbuds capable of detecting signs of drowsiness in the brain to protect drivers and machine operators from the dangers of falling asleep at the wheel.
The earbuds detect brain waves similar to an electroencephalogram (EEG), a test doctors use to measure electrical activity in the brain. While most EEGs use electrodes attached to the head to detect brain waves, the earbuds have built-in electrodes designed to make contact with the ear canal for the same purpose.
The electrical signals detected by the earbuds are smaller than those picked up by a traditional EEG. However, a new study by the researchers shows that their Ear EEG platform is sensitive enough to detect alpha waves, a pattern of brain activity that increases when you close your eyes or start to fall asleep.
“I was inspired when I bought my first pair of Apple’s AirPods in 2017. I immediately thought, ‘What an amazing platform for neural recording,'” said study senior author Rikky Muller, an associate professor of electrical engineering and computer sciences at UC Berkeley. “We believe that this technology has many potential uses. Classifying drowsiness is a good indicator that the technology can be used to classify sleep and even diagnose sleep disorders.”
Using an earbud as an EEG electrode presents several practical challenges. The electrodes must maintain good contact with the skin to obtain an accurate EEG reading. This is relatively simple to achieve with traditional EEGs, which use flat metal electrodes attached to the scalp. However, it is more challenging to design an earbud that will fit securely and comfortably in ears of various sizes and shapes.
“When Muller’s team began working on the project, other groups developing Ear EEG platforms used wet electrode gels to ensure a good seal between the earbud and the ear canal or create custom-moulded earpieces for each user. She and her team aimed to design a dry and universally applicable model, allowing anyone to insert them in their ears and obtain reliable readings.”
“My personal goal was to create a device that could be used daily by individuals who would greatly benefit from it,” explained Ryan Kaveh, a postdoctoral scholar at UC Berkeley and co-first author of the study. “To achieve this, I understood that it needed to be reusable, adaptable to various people, and simple to manufacture.”
Kaveh co-led the study with graduate student Carolyn Schwendeman and collaborated with Ana Arias’s lab at UC Berkeley to design the final earpiece in three sizes: small, medium, and large. The earpiece incorporates multiple electrodes in a cantilevered design that applies gentle outward pressure to the ear canal and uses flexible electronics to ensure a comfortable fit. The signals are read through a custom, low-power, wireless electronic interface.
In a 2020 paper, researchers demonstrated that these earpieces can detect various physiological signals, such as eye blinks, alpha brain waves, and the auditory steady-state response, which is the brain’s reaction to hearing a constant pitch. In the new study, they enhanced the earpiece design and utilized machine learning to show how the earpieces could be applied in real-world scenarios.
During the experiment, nine volunteers were asked to wear earpieces while performing mundane tasks in a dimly lit room. Periodically, the volunteers rated their level of drowsiness and measured their response times.
“We discovered that even when the signal quality from the earpieces appeared to be worse, we were still able to accurately detect the onset of drowsiness, just as effectively as much more complicated, bulky systems,” Kaveh explained. The earpieces also maintain their accuracy when identifying drowsiness in new users, a feature that makes them suitable for use right out of the box.”
“Developed with the support of the Bakar Fellowship and the Bakar Prize, Muller is continuing to refine the design of the Ear EEG and explore other potential applications of the device. In addition to recording EEG signals, the device can also record other signals such as heartbeats, eye movements, and jaw clenches.”
“We constantly wear wireless earbuds,” Muller explained. “That’s what makes Ear EEG so compelling. It doesn’t require anything extra.”
A recent early-stage stem cell therapy trial has demonstrated promising results in treating progressive MS.
An international team has shown that the injection of a type of stem cell into the brains of patients living with progressive multiple sclerosis (MS) is safe, well tolerated and has a long-lasting effect that appears to protect the brain from further damage.
The study, led by scientists at the University of Cambridge, University of Milan Bicocca and Hospital Casa Sollievo della Sofferenza (Italy), is a step towards developing an advanced cell therapy treatment for progressive MS.
Over 2 million people live with MS worldwide, and while treatments exist that can reduce the severity and frequency of relapses, two-thirds of MS patients still transition into a debilitating secondary progressive phase of disease within 25-30 years of diagnosis, where disability grows steadily worse.
In MS, the body’s own immune system attacks and damages myelin, the protective sheath around nerve fibres, causing disruption to messages sent around the brain and spinal cord.
Key immune cells involved in this process are macrophages (literally ‘big eaters’), which ordinarily attack and rid the body of unwanted intruders. A type of macrophage known as a microglial cell is found throughout the brain and spinal cord. In progressive forms of MS, they attack the central nervous system (CNS), causing chronic inflammation and damage to nerve cells.
Recent advances have raised expectations that stem cell therapies might help ameliorate this damage. These involve the transplantation of stem cells, the body’s ‘master cells’, which can be programmed to develop into almost any cell type within the body.
Previous work from the Cambridge team has shown in mice that skin cells re-programmed into brain stem cells, and transplanted into the central nervous system, can help reduce inflammation and may be able to help repair damage caused by MS.
Now, in research published in the Cell Stem Cell, scientists have completed a first-in-man, early-stage clinical trial that involved injecting neural stem cells directly into the brains of 15 patients with secondary MS recruited from two hospitals in Italy. The trial was conducted by teams at the University of Cambridge, Milan Bicocca and the Hospitals Casa Sollievo della Sofferenza and S. Maria Terni (IT) and Ente Ospedaliero Cantonale (Lugano, Switzerland) and the University of Colorado (USA).
The stem cells were derived from cells taken from brain tissue from a single, miscarried foetal donor. The Italian team had previously shown that it would be possible to produce a virtually limitless supply of these stem cells from a single donor – and in future it may be possible to derive these cells directly from the patient – helping to overcome practical problems associated with the use of allogeneic foetal tissue.
The team followed the patients over 12 months, during which time they observed no treatment-related deaths or serious adverse events. While some side-effects were observed, all were either temporary or reversible.
All the patients showed high levels of disability at the start of the trial – most required a wheelchair, for example – but during the 12 month follow up period none showed any increase in disability or a worsening of symptoms. None of the patients reported symptoms that suggested a relapse and nor did their cognitive function worsen significantly during the study. Overall, say the researchers, this points to a substantial stability of the disease, without signs of progression, though the high levels of disability at the start of the trial make this difficult to confirm.
The researchers assessed a subgroup of patients for changes in the volume of brain tissue associated with disease progression. They found that the larger the dose of injected stem cells, the smaller the reduction in this brain volume over time. They speculate that this may be because the stem cell transplant dampened inflammation.
The team also looked for signs that the stem cells were having a neuroprotective effect – protecting nerve cells from further damage. Their previous work showed how tweaking metabolism – how the body produces energy – can reprogram microglia from ‘bad’ to ‘good’. This new study looked at how the brain’s metabolism changes after the treatment. They measured changes in the fluid around the brain and in the blood over time and found certain signs linked to how the brain processes fatty acids. These signs were connected to how well the treatment works and how the disease develops. The higher the dose of stem cells, the greater the levels of fatty acids, which also persisted over the 12-month period.
Professor Stefano Pluchino from the University of Cambridge, who co-led the study, said: “We desperately need to develop new treatments for secondary progressive MS, and I am cautiously very excited about our findings, which are a step towards developing a cell therapy for treating MS.
“We recognise that our study has limitations – it was only a small study and there may have been confounding effects from the immunosuppressant drugs, for example – but the fact that our treatment was safe and that its effects lasted over the 12 months of the trial means that we can proceed to the next stage of clinical trials.”
Co-leader Professor Angelo Vescovi from the University of Milano-Bicocca said: “It has taken nearly three decades to translate the discovery of brain stem cells into this experimental therapeutic treatment This study will add to the increasing excitement in this field and pave the way to broader efficacy studies, soon to come.”
Caitlin Astbury, Research Communications Manager at the MS Society, says: “This is a really exciting study which builds on previous research funded by us. These results show that special stem cells injected into the brain were safe and well-tolerated by people with secondary progressive MS. They also suggest this treatment approach might even stabilise disability progression. We’ve known for some time that this method has the potential to help protect the brain from progression in MS.
“This was a very small, early-stage study and we need further clinical trials to find out if this treatment has a beneficial effect on the condition. But this is an encouraging step towards a new way of treating some people with MS.”