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1  Tutkimus / Tutkimus / Re: Suolistobakteerit, myeliini ja aivotoiminta
 Pvm: 08.06.2021 - 20:51:34 
Keskustelun aloitti HopeSprings | Kirjoittaja HopeSprings  
Microbes may hold the key for treating neurological disorders

https://www.sciencedaily.com/releases/2021/03/210310122535.htm

March 10, 2021


When we think about the causes of neurological disorders and how to treat them, we think about targeting the brain. But is this the best or only way? Maybe not. New research by scientists at Baylor College of Medicine suggests that microbes in the gut may contribute to certain symptoms associated with complex neurological disorders. The findings, published in the journal Cell, also suggest that microbe-inspired therapies may one day help to treat them.

Dr. Mauro Costa-Mattioli, professor and Cullen Foundation Endowed Chair in neuroscience and director of the Memory and Brain Research Center at Baylor, discovered with his team that different abnormal behaviors are interdependently regulated by the host's genes and microbiome. Specifically, the team found that in mouse models for neurodevelopmental disorders, hyperactivity is controlled by the host's genetics, whereas social behavior deficits are mediated by the gut microbiome.

More importantly from a therapeutic perspective, they found that treatment with a specific microbe that promotes the production of compounds in the biopterin family in the gut or treatment with a metabolically active biopterin molecule improved the social behavior but not motor activity.

"We are the bearers of both host and microbial genes. While most of the focus has traditionally been in host genes, the gut microbiome, the community of microorganisms that live within us, is another important source of genetic information," Costa-Mattioli said.

The work by Costa-Mattioli's group offers a different way of thinking about neurological disorders in which both human and microbial genes interact with each other and contribute to the condition. Their findings also suggest that effective treatments would likely need to be directed at both the brain and the gut to fully address all symptoms. Additionally, they open the possibility that other complex conditions, such as cancer, diabetes, viral infection or other neurological disorders may have a microbiome component.

Brain-gut-microbiome crosstalk

"It's very difficult to study these complex interactions in humans, so in this study, we worked with a mouse model for neurodevelopmental disorders in which the animals lacked both copies of the Cntnap2 gene (Cntnap2-/- mice)," said co-first author Sean Dooling, a Ph.D. candidate in molecular and human genetics in the Costa-Mattioli lab. "These mice presented with social deficits and hyperactivity, similar to those observed in autism spectrum disorders (ASD). In addition, these mice, like many people with ASD, also had changes in the bacteria that make up their microbiome compared to the mice without the genetic change."

Further experiments showed that modulating the gut microbiome improved the social behavior in the mutant mice, but did not alter their hyperactivity, indicating that the changes in the microbiome selectively contribute to the animals' social behavior.

"We were able to separate the contribution of the microbiome and that of the animal's genetic mutation on the behavioral changes," Dooling said. "This shows that the gut microbiome shouldn't be ignored as an important variable in studying health and disease."

Equipped with this knowledge, the researchers dug deeper into the mechanism underlying the microbiome's effect on the animal's social deficits. Based on their previous work, the investigators treated the mice with the probiotic microbe, L. reuteri.

"We found that L. reuteri also can restore normal social behavior but cannot correct the hyperactivity in Cntnap2-/- mice," said co-first author Dr. Shelly Buffington, a former postdoctoral fellow in the Costa-Mattioli lab and now an assistant professor at the University of Texas Medical Branch in Galveston.

However, the bigger surprise came when the investigators administered to the asocial mice a metabolite or compound they found was increased in the host's gut by L. reuteri. They discovered that the animals' social deficits also were improved after treating them with the metabolite instead of the bacteria.

"This provides us with at least two possible ways to modulate the brain from the gut, with the bacteria or the bacteria-induced metabolite," said Buffington.

Bacteria to heal your brain & beyond

Could this work inspire new breakthroughs in treating neurological disorders? While it is still too early to say for sure, the investigators are particularly excited about the translational implications of their findings. "Our work strengthens an emerging concept of a new frontier for the development of safe and effective therapeutics that target the gut microbiome with selective probiotic strains of bacteria or bacteria-inspired pharmaceuticals," Buffington said.

"As we learn more about how these bacteria work, we will be able to more precisely and effectively leverage their power to help treat the brain and perhaps more," Dooling added.

This research represents important step forward in the field as many disorders, especially those affecting the brain, remain very difficult to treat.

"Despite all the scientific advances and the promise of gene manipulation, it is still difficult to modulate human genes to treat diseases, but modulating our microbiome may be an interesting, noninvasive alternative," said Costa-Mattioli. Indeed, L. reuteri currently is being tested in a clinical trial in Italy in children with autism, and Costa-Mattioli aims to start his own trial soon.

"In my wildest dreams, I could have never imagined that microbes in the gut could modulate behavior and brain function. To think now that microbial-based strategies may be a viable way to treat neurological dysfunction, is still wild, but very exciting."


2  Tutkimus / Tutkimus / Re: Suolistobakteerit, myeliini ja aivotoiminta
 Pvm: 08.06.2021 - 20:46:10 
Keskustelun aloitti HopeSprings | Kirjoittaja HopeSprings  
New evidence links gut bacteria and neurodegenerative conditions

https://www.sciencedaily.com/releases/2021/05/210506142109.htm

May 6, 2021

Neurodegenerative diseases such as Alzheimer's, Parkinson's and ALS affect millions of adults, but scientists still do not know what causes these diseases, which poses a significant roadblock to developing treatments or preventative measures.

Recent research suggests that people with these conditions exhibit changes in the bacterial composition of their digestive tract. However, given the vast diversity of microbes found in the human body, identifying which bacteria may be associated with neurodegeneration is like finding a needle in a haystack.

Seeking that proverbial needle, scientists at the University of Florida are looking in an unexpected place: the digestive tract of a tiny, translucent worm called Caenorhabditis elegans.

New research published in PLOS Pathogens establishes, for the first time, a link between specific bacteria species and physical manifestations of neurodegenerative diseases. The study's lead author is Alyssa Walker, a microbiology and cell science doctoral candidate in the UF/IFAS College of Agricultural and Life Sciences.

"Looking at the microbiome is a relatively new approach to investigating what causes neurodegenerative diseases. In this study, we were able to show that specific species of bacteria play a role in the development of these conditions," said Daniel Czyz, Walker's dissertation advisor.

Czyz is the senior author of the study and an assistant professor in the UF/IFAS department of microbiology and cell science.

"We also showed that some other bacteria produce compounds that counteract these 'bad' bacteria. Recent studies have shown that patients with Parkinson's and Alzheimer's disease are deficient in these 'good' bacteria, so our findings may help explain that connection and open up an area of future study," he added.

All neurodegenerative diseases can be traced to problems with the way proteins are handled in the body. If proteins are misfolded, they build up and accumulate in tissues. These protein aggregates, as scientists call them, interfere with cell functioning and lead to neurodegenerative disorders.

Czyz and his co-authors wanted to know if introducing certain bacteria into the C. elegans worms would be followed by protein aggregation in the worms' tissues.

"That is, in fact, what we observed. We have a way of marking the aggregates so they glow green under the microscope. We saw that worms colonized by certain bacteria species were lit up with aggregates that were toxic to tissues, while those colonized by the control bacteria were not," Czyz said. "This occurred not just in the intestinal tissues, where the bacteria are, but all over the worms' bodies, in their muscles, nerves and even reproductive organs."

Surprisingly, the offspring of affected worms also showed increased protein aggregation -- even though these offspring never encountered the bacteria originally associated with the condition.

"This is very interesting because it suggests that these bacteria generate some sort of a signal that can be passed along to the next generation," Czyz said.

Worms colonized by the "bad" bacteria also lost mobility, a common symptom of neurodegenerative diseases.

"A healthy worm moves around by rolling and thrashing. When you pick up a healthy worm, it will roll off the pick, a simple device that we use to handle these tiny animals. But worms with the bad bacteria couldn't do that because of the appearance of toxic protein aggregates," explained Walker, who developed this assessment method.

"You could compare the pick to an obstacle course: just as a person with a neurodegenerative disease will have trouble getting across, the same is true with these worms, just at a much smaller scale," Czyz added.

Fun fact: Human eyebrow hairs or eyelashes make for very good picks.

"The worms are very delicate, so you need a tool that won't damage them. They are also transparent and have a simple body plan. Studies like ours are possible because these worms normally feed on bacteria," Czyz said.

"The worms are only one millimeter long, and they each have exactly 959 cells," Czyz said. "But in many ways, they are a lot like us humans -- they have intestines and muscles and nerves, but instead of being composed of billions of cells, each organ is just a handful of cells. They are like living test tubes. Their small size allows us to do experiments in a much more controlled way and answer important questions we can apply in future experiments with higher organisms and, eventually, people."

Currently the Czyz lab is testing hundreds of strains of bacteria found in the human gut to see how they affect protein aggregation in C. elegans. The group is also investigating how bacteria associated with neurodegeneration cause protein misfolding at the molecular level.

Czyz is also interested in possible connections between antibiotic-resistant bacteria and protein misfolding.

"Almost all of the bacteria we found associated with protein misfolding are also associated with antibiotic-resistant infections in people. However, it will take many more years of research before we can understand what, if any, connection there is between antibiotic resistance and neurodegenerative diseases," Czyz said.

3  Tutkimus / Tutkimus / Exoskeleton terapia
 Pvm: 08.06.2021 - 20:38:10 
Keskustelun aloitti HopeSprings | Kirjoittaja HopeSprings  
Exoskeleton therapy improves mobility, cognition and brain connectivity in people with MS


https://www.sciencedaily.com/releases/2021/05/210528133442.htm

May 28, 2021

A team of multiple sclerosis (MS) experts at Kessler Foundation led the first pilot randomized controlled trial of robotic-exoskeleton assisted exercise rehabilitation (REAER) effects on mobility, cognition, and brain connectivity in people with substantial MS-related disability. Their results showed that REAER is likely an effective intervention, and is a promising therapy for improving the lives of those with MS.

It is common for people with MS to experience impairments in both mobility and cognition, and few therapies exist to manage the range of debilitating symptoms. This lack of treatment options is a major problem for people with MS, especially those with substantial MS-related neurological disability.

Previous research shows that exercise rehabilitation, such as walking, is an effective approach to symptom management, with some research suggesting that even a single exercise rehabilitation intervention can improve both mobility and cognition.

Yet there is a lack of efficacy of exercise rehabilitation on mobility and cognitive outcomes in people with MS who have substantial disability. Adaptive exercise rehabilitation approaches such as body-weight supported treadmill training and robot-assisted gait training have not demonstrated convincing results. Moreover, adaptive interventions lack key interactions between patients and therapists that may improve efficacy.

In this pilot study of 10 participants with significant MS-related neurological disability, researchers explored the use of robotic exoskeletons to manage symptoms. Rehabilitation exercise using robotic exoskeletons is a relatively new approach that enables participants to walk over-ground in a progressive regimen that involves close engagement with a therapist. The Foundation has dedicated a Ekso NR to MS studies to facilitate further research in this area.

As compared to conventional gait training, REAER allows participants to walk at volumes needed to realize functional adaptations -- via vigorous neurophysiological demands -- that lead to improved cognition and mobility. Effects on brain activity patterns were studied using the functional MRI capabilities of the Rocco Ortenzio Neuroimaging Center at Kessler Foundation.

Investigators compared participants' improvement after four weeks of REAER vs four weeks of conventional gait training, looking at functional mobility, walking endurance, cognitive processing speed, and brain connectivity.

The results were positive: Relative to conventional gait training, four weeks of REAER was associated with large improvements in functional mobility (?p2=.38), cognitive processing speed (?p2=.53), and brain connectivity outcomes, most significantly between the thalamus and ventromedial prefrontal cortex (?p2=.72). "Four weeks is relatively short for an exercise training study," noted Dr. Sandroff, senior research scientist at Kessler Foundation and director of the Exercise Neurorehabilitation Research Laboratory. "Seeing improvements within this timeframe shows the potential for exercise to change how we treat MS. Exercise is really powerful behavior that involves many brain regions and networks that can improve over time and result in improved function."

"This is particularly exciting because therapy using robotic exoskeletons shows such promise for improving the lives of people with co-occurring mobility and cognitive disability, a cohort that likely has the greatest potential to benefit from this new technology," said Dr. Androwis, lead author and research scientist in the Center for Mobility and Rehabilitation Engineering Research at Kessler Foundation. "We're eager to design a larger trial to further study these effects. Based on our initial results, we're optimistic that this approach may be superior to the current standard of care."

4  Tutkimus / Tutkimus / Re: Krooniset bakteeri-infektiot
 Pvm: 08.06.2021 - 20:33:15 
Keskustelun aloitti HopeSprings | Kirjoittaja HopeSprings  
EBV infection and MS risk genes work together to facilitate MS

https://msra.org.au/news/ebv-infection-and-ms-risk-genes/

22 May, 2019

  - Infection with Epstein-Barr Virus (EBV) is one of the known risk factors of developing MS but how EBV relates to MS risk is still an open question.
  - New research by Australian researchers has looked at the effect of EBV infection on genetic activity in immune cells.
  - Findings showed that EBV controls some MS risk genes.

What is Epstein Barr Virus (EBV)?

EBV (the virus that causes glandular fever) is a virus that belongs to the herpes virus family and it infects a type of immune cell in the blood known as a B cell. Once a person has been infected with EBV they carry the virus in their B cells for life, meaning their body has to continually control the EBV infection for the rest of their lifetime.

What do we already know about the link between EBV and MS?

Infection with EBV has long been known to be associated with the development of MS. However, while the majority of the population has been infected with the virus (only a small percent will develop recognisable symptoms), 100% of those with MS are thought to be infected.

This shows that while EBV plays a huge role in MS an EBV infection is not sufficient by itself to cause MS. So why do some people who contract EBV develop MS yet others never do? Part of the answer may lie in our genetics.

Previous research funded by MS Research Australia by Professor Michael Pender has shown that people with MS inadequately control these EBV hijacked immune cells and now Australian scientists might have uncovered an interesting interplay between the MS genetic risk factors and EBV.

A new link discovered between EBV and MS risk genes

In a new study, researchers at the Westmead Institute of Medical Research have investigated the way that EBV infection changes which genes the B cells are using and hence changes the way these cells act. Published in Genome Medicine, the researchers compared the gene activity of B cells that were infected with EBV and grown in the laboratory, and cells that had not been infected. They were particularly interested to see whether there would be any changes in the 200+ genetic elements that have already been identified as risk factors for the development of MS.

The research findings explained…

The research showed that a significant proportion of these MS risk genes were influenced by the presence of EBV. This means that:

  - The infected cells used the MS risk genes differently in the presence of EBV.
  -Some of these genes, in turn, controlled other genes in the cell, meaning there was a domino effect resulting in a number of changes within the cell.
  - Further experiments showed that EBV may drive some of these changes at a cellular level through the binding of a molecule called EBNA2. When EBV is hijacking a cell it might try and use a number of cellular genes, and a portion of those are already known as MS risk genes.

This study indicates that the MS risk genes may be working together with EBV infection to facilitate the development of MS and that this interaction may be one way genetic changes act at a biological level to increase the risk of MS.

What do these new findings mean for the future?

A better understanding of the way that EBV infection relates to MS development is important to drive new therapeutic approaches for this disease. Professor Michael Pender’s work has led to the development of a new treatment strategy, currently in clinical trials, based on the idea that boosting a person with MS’s ability to control ongoing EBV infection could help treat MS.

5  Tutkimus / Tutkimus / Re: Krooniset bakteeri-infektiot
 Pvm: 08.06.2021 - 20:29:18 
Keskustelun aloitti HopeSprings | Kirjoittaja HopeSprings  
Australian EBV Progressive MS trial: Three years on

https://msra.org.au/news/ebv-progressive-ms-trial-three-years-on/

18 May, 2021

 - A treatment called ‘adoptive T cell immunotherapy’ – which targets the Epstein Barr virus (EBV) – was shown to be safe in a group of 10 people with progressive MS in a small phase I (safety) trial back in 2018.
  - The treatment takes the person’s T cells from the immune system and boosts their capacity to recognise and kill EBV-infected cells.
  - EBV has long been implicated in the development of MS.
  - The scientists now report on the participants’ clinical outcomes three years after they received the treatment.

In 2018 MS Research Australia announced the outcomes of a novel, cutting-edge clinical trial. This trial, funded by MS Research Australia and MS QLD, aimed to test a new treatment option for people with progressive MS. The treatment was a new method called ‘adoptive T cell immunotherapy’ – which targets the Epstein Barr virus (EBV). This trial was an early-stage trial designed to test this treatment option’s safety, an essential step of earlier trials.

The procedure involves taking blood from participants and extracting T cells, which are immune cells that recognize and kill specific cells, such as virus-infected or cancer cells. From this T cell mix, cells that target EBV are specifically expanded to create a powerful “immune arsenal” against EBV. The cells are then reintroduced to the person’s body and target the EBV hiding in the body.

Initial clinical trial

Initially, the trial was carried out by Professor Michael Pender from The University of Queensland and Professor Rajiv Khanna AO from QIMR Berghofer Medical Research Institute. MS Research Australia is proud to have contributed to the funding of this project and significantly supported Professor Pender’s EBV research over the last decade. You can read more on this research and the original trial here.

Professor Pender and his team have now followed up on the original participants in the trial, and their findings have just been published in the journal Frontiers in Neurology.

Three years on

Following the trial, the researchers collected data at the two year mark from 10 participants who had received the treatment and then again at the three year mark from 9 participants. No serious treatment-related adverse events were observed. Four participants had at least some sustained clinical improvement at year two, including reduced fatigue in three participants and reduced disability in two participants. Three participants experienced a sustained improvement in at least some symptoms at year three. More sustained clinical improvement was associated with better EBV-targeting power of the reinfused cells (ie higher percentage of T cells specifically recognizing EBV).

They conclude from this follow-up study that this treatment is well-tolerated and can provide some degree of clinical improvement, sustained for up to three years after treatment. Once again, this is based on small numbers of participants and the trial was designed mainly to test the safety of this treatment option.
Future directions for adoptive T cell immunotherapy

The next steps of this research are underway, and a further clinical trial has started. It is important to note that there are slight differences between the follow-up trial and the original trial. In the original trial, the process involved taking cells from a person with MS, boosting their EBV-killing capacity, and then reintroducing those cells to the same person. In the next iteration, the researchers are using EBV-targeted cells, but this time collected from a healthy unrelated donor instead of the person themselves. This iteration aims to be more scalable, allowing the researchers to treat more participants more efficiently and ensure highly efficient targeting of EBV, and early indications from clinical study have provided encouraging results. These studies have now been extended to a Randomized, Placebo-Controlled Phase 2 Study.

This is an important study as it is a novel way to treat MS, and is also targeting progressive MS, a form of MS for which, unfortunately, we have very few treatment options. We look forward to bringing you the results of the next stage of these trials.

6  Tutkimus / Tutkimus / PET- ja diffuusiotensorikuvantaminen
 Pvm: 07.06.2021 - 10:15:13 
Keskustelun aloitti merikihu | Kirjoittaja merikihu  
"FM Jouni Tuisku kehitti Turun yliopistossa tarkastettavassa väitöstutkimuksessaan kuvantamismenetelmiä MS-taudista johtuvien valkean aineen molekulaaristen ja rakenteellisten muutosten selvittämiseksi. Tutkimuksessa osoitettiin ensimmäistä kertaa PET- ja diffuusiotensorikuvantamisen avulla, että hermosolujen tulehdusreaktio on yhteydessä aivojen rakenteelliseen vaurioon MS-potilaiden aivojen terveeltä vaikuttavassa valkeassa aineessa. Tutkimustuloksia voidaan hyödyntää tulevissa MS-tautiin liittyvissä lääketutkimuksissa, joissa lääkkeiden vaikutusta voidaan havainnoida kuvantamisen avulla."

https://www.utu.fi/fi/ajankohtaista/vaitos/vaittelija-kehitti-kuvantamismenetelm...

7  Yleinen / MS-jutut / Re: Koronarokote
 Pvm: 04.06.2021 - 11:55:46 
Keskustelun aloitti admin | Kirjoittaja kissankello69  
Hei!
Sain n. kk sitten Pfizerin comirnaty -rokotteen. Minulle ei myöskään muuta oireita tullut kuin käsi oli kipeä pari päivää. En käytä enää mitään ms-lääkettä. Iho ei kestä enää pistoksia ja tablettilääkkeet eivät sopineet vatsaoireidenkaan vuoksi (minulla on myös refluksi). Toinen rokoteannos on tulossa sitten elokuun alussa.

8  Yleinen / MS-jutut / Re: Koronarokote
 Pvm: 02.06.2021 - 07:32:20 
Keskustelun aloitti admin | Kirjoittaja merikihu  
Sain Astra Zenecan kaksi viikkoa sitten. Käsivarren pistoskohta oli vähän kipeä pari päivää, siinä kaikki sivuoireet. Minulla on lymfosyyttejä alentava lääkitys (Tecfidera). Neurologi sanoi, että kaikki luvan saaneet koronarokotteet käyvät minulle.

9  Yleinen / MS-jutut / Re: Koronarokote
 Pvm: 01.06.2021 - 21:30:24 
Keskustelun aloitti admin | Kirjoittaja Sateenkaari  
Moi kaikille, olen uusi täällä 😊
MrMS tuossa kertoikin, että minkälaista haittavaikutusta olit koronarokotteesta saanut. Kiinnostaisi kuulla muidenkin kokemuksia, että minkälaisia vaikutuksia olette rokotteesta saaneet?
Vaikuttiko teillä mitenkään se, jos teillä on vastustuskykyä/lymfosyyttejä alentava lääkitys?

10  Yleinen / MS-jutut / Re: Henkilökohtainen avustaja
 Pvm: 29.05.2021 - 15:36:59 
Keskustelun aloitti tinttura64 | Kirjoittaja Neilikkamies  
Olen ollut tk-eläkkeellä vuodesta 2014. Taksikyydit ollut vuoden ja Kela-korvattua jatkuva avokuntoutus.

Mulla kuntoutusohjaaja teki kotikäynnin ja puhuimme avustajasta. Lääkäri kirjoitti lausunnon, jossa suositeltiin henkilökohtaista avustajaa tukemaan itsenäistä selviytymistä kotona. Avustaja käy kahdesti viikossa 4 tuntia kerrallaan.