Day: January 17, 2025

Categories : Neurodegenerative Diseases New Compounds and TreatmentsTags : Leave a comment

Noble Intentions: Xenon Gas might Protect against Alzheimer’s

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By Alchemist-hp (talk) (www.pse-mendelejew.de) – Own work, FAL

Most treatments being pursued today to protect against Alzheimer’s disease focus on amyloid plaques and tau tangles that accumulate in the brain, but new research from Mass General Brigham and Washington University School of Medicine in St. Louis points to a novel – and noble – approach: using xenon gas. The study found that xenon gas inhalation suppressed neuroinflammation, reduced brain atrophy, and increased protective neuronal states in mouse models of Alzheimer’s disease. Results are published in Science Translational Medicine, and a phase 1 clinical trial of the treatment in healthy volunteers will begin in early 2025.

“It is a very novel discovery showing that simply inhaling an inert gas can have such a profound neuroprotective effect,” said senior and co-corresponding author Oleg Butovsky, PhD, at Brigham and Women’s Hospital (BWH). “One of the main limitations in the field of Alzheimer’s disease research and treatment is that it is extremely difficult to design medications that can pass the blood-brain barrier – but senon gas does. We look forward to seeing this novel approach tested in humans.”

“It is exciting that in both animal models that model different aspects of Alzheimer’s disease, amyloid pathology in one model and tau pathology in another model, that Xenon had protective effects in both situations,” said senior and co-corresponding author David M. Holtzman, MD, from Washington University School of Medicine in St. Louis.

The causes of Alzheimer’s disease are not fully understood; there is currently no cure, and more effective treatments are desperately needed. Characterised by protein buildups in the brain, including tau and amyloid, Alzheimer’s disease disrupts nerve cell communication and causes progressive brain abnormalities that lead to neuronal damage and ultimately to death. Microglia, the brain’s primary and most prominent immune cells, act as ‘first responders’ when something goes awry in the brain, and they play a key role in regulating brain function in all phases of development. Microglial dysregulation is a key component of Alzheimer’s disease. Butovsky’s lab previously designed a way to study how microglia respond to neurodegeneration and confirmed that a specific phenotype of microglia can be modulated in a way that is protective in Alzheimer’s disease.

In this study, mouse models of Alzheimer’s disease were treated with xenon gas that has been used in human medicine as an anesthetic and as a neuroprotectant for treating brain injuries. Xenon gas penetrates the blood-brain barrier, passing from the bloodstream directly into the fluid surrounding the brain. The team found that xenon gas inhalation reduced brain atrophy and neuroinflammation and improved nest-building behaviours in the Alzheimer’s disease mouse models. It also induced and increased a protective microglial response that is associated with clearing amyloid and improving cognition. Together, these findings identify the promising potential of xenon inhalation as a therapeutic approach that could modify microglial activity and reduce neurodegeneration in Alzheimer’s disease.

The clinical trial at Brigham and Women’s Hospital, which will initially only enrol healthy volunteers, is set to begin in the next few months.

As early phases of the clinical trial get underway to establish safety and dosage, the research team plans to continue to study the mechanisms by which xenon gas achieves its effects in addition to its potential for treating other diseases such as multiple sclerosis, amyotrophic lateral sclerosis, and eye diseases that involve the loss of neurons. The team is also devising technologies to help use xenon gas more efficiently as well as potentially recycle it.

“If the clinical trial goes well, the opportunities for the use of Xenon gas are great,” said co-author Howard Weiner, MD, co-director of the Ann Romney Center for Neurologic Diseases at BWH and principal investigator of the upcoming clinical trial. “It could open the door to new treatments for helping patients with neurologic diseases.”

Source: Mass General Brigham

Categories : Diet and Nutrition VaccinesTags : Leave a comment

Study in SA Children Finds Undernutrition may Weaken Measles Vaccination

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Photo by National Cancer Institute

Amid a global surge in measles cases, new research suggests that undernutrition may be exacerbating outbreaks in areas suffering from food insecurity. A study involving over 600 fully vaccinated children in South Africa found those who were undernourished had substantially lower levels of antibodies against measles.

Researchers from McGill University, UC Berkeley School of Public Health and the University of Pretoria tracked the children’s growth over time as an indicator of undernutrition and measured their antibody levels through blood tests. Children who were stunted around age three had an average of 24-per-cent-lower measles antibody levels by age five compared to their typical-sized peers.

The findings, published in Vaccine, suggest that undernutrition may affect the duration of vaccine protection.

This indicates that addressing child hunger could be a key piece of the puzzle in preventing viral outbreaks, said senior author Jonathan Chevrier, an Associate Professor at McGill.

A growing threat worldwide

Measles is a highly contagious viral infection that causes symptoms such as a rash, fever and cough, and can lead to severe complications, especially in young children. The disease is a threat in regions where it was once under control, including Canada, which in 2024 reported its highest number of cases in nearly a decade.

“Global measles cases declined from 2000 to 2016, but the trend reversed in 2018, driven in part by under-vaccination and the impact of the pandemic. Measles is now making a strong comeback in many parts of the world despite being preventable with vaccination and adequate immunity,” said co-author Brian Ward, Professor at McGill’s.

“We need to vaccinate children against infectious diseases that are preventable and ensure they are protected,” said first author Brenda Eskenazi, Professor at the University of California, Berkeley. “This is especially important now, given that many known diseases are expected to spread with climate change.”

About 22% of children under age five worldwide – approximately 148 million – were stunted in 2022, Chevrier added, with the highest rates in Asia and sub-Saharan Africa.

The team plans to monitor the children in the study as they grow older to understand whether the effects of early-life undernutrition persist.

Source: McGill University

Categories : DermatologyTags : Leave a comment

Sunburn Results from Damage to RNA, not DNA

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The warnings against sunburn are well known: avoid direct sunlight between 12 noon and 3pm, seek out shade and put on sunscreen and a hat. It is also taught that sunburn results from damage to DNA. But that is not the full truth, according the researchers behind a new study conducted at the University of Copenhagen and Nanyang Technological University, Singapore (NTU Singapore).

“Sunburn damages the DNA, leading to cell death and inflammation. So the textbooks say. But in this study we were surprised to learn that this is a result of damage to the RNA, not the DNA that causes the acute effects of sunburn,” says Assistant Professor Anna Constance Vind, who is one of the researchers responsible for the new study.

The study has been published in Molecular Cell.

RNA is a more transient molecule than DNA. A type of RNA, known as messenger RNA (mRNA), functions as the intermediate ‘messenger’ that carries information from DNA to make proteins – the basic building blocks of cellular components.

“DNA damage is serious as the mutations will get passed down to progenies of the cells, RNA damage happens all the time and does not cause permanent mutations. Therefore, we used to believe that the RNA is less important, as long as the DNA is intact. But in fact, damages to the RNA are the first to trigger a response to UV radiation,” Anna Constance Vind explains.

The new study was conducted on mice as well as human skin cells, and the objective was to describe the impact of UV radiation on the skin and what causes these damages. The researchers found the same skin response to UV radiation exists in both mice and human cells.

A built-in surveillance system for RNA damage

mRNA damage triggers a response in ribosomes (protein complexes that “read” the mRNA to synthesise protein), orchestrated by a protein known as ZAK-alpha – the so-called ribotoxic stress response – the new study shows. The response can be described as a surveillance system within the cells, which registers the RNA damage, leading to inflammatory signalling and recruitment of immune cells, which then leads to inflammation of the skin.

“We found that the first thing the cells respond to after being exposed to UV radiation is damage to the RNA, and that this is what triggers cell death and inflammation of the skin. In mice exposed to UV radiation we found responses such as inflammation and cell death, but when we removed the ZAK gene, these responses disappeared, which means that ZAK plays a key role in the skin’s response to UV-induced damage,” says Professor Simon Bekker-Jensen from the Department of Cellular and Molecular Medicine, who is one of the other researchers responsible for the study. He adds:

“So you could say that everything depends on this one response, which monitors all protein translations occurring. The cells respond to the RNA damage, realising that something is wrong, and this is what leads to cell death.”

Faster and more effective response

The result of the study changes our understanding of sunburn and the skin’s defence mechanisms: that RNA damage triggers a faster and more effective response, protecting the skin from further damage.

“The fact that the DNA does not control the skin’s initial response to UV radiation, but that something else does and that it does so more effectively and more quickly, is quite the paradigm shift,” says Anna Constance Vind.

We need to understand the function of RNA damage, as it may in the long term change our entire approach to prevention and treatment of sunburn.

“Many inflammatory skin diseases are worsened by sun exposure. Thus, understanding how our skin responds at the cellular level to UV damage opens the door to innovative treatments for certain chronic skin conditions,” says co-author Dr Franklin Zhong, Nanyang Assistant Professor at NTU’s Lee Kong Chian School of Medicine.

“This new knowledge turns things upside down. I think most people associate sunburn with DNA damage; it is established knowledge. But now we need to rewrite the textbooks, and it will affect future research on the effects of UV radiation on the skin,” Simon Bekker-Jensen concludes.

Source: University of Copenhagen

Categories : Diet and Nutrition Metabolic DisordersTags : Leave a comment

Millions of Diabetes and Heart Disease Cases Linked to Sugary Drinks, New Study Finds

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A new study from researchers at Tufts University, which appears in Nature Medicine, estimates that 2.2 million new cases of type 2 diabetes and 1.2 million new cases of cardiovascular disease occur each year globally due to consumption of sugar-sweetened beverages.

In developing countries, the case count is particularly sobering. In Sub-Saharan Africa, the study found that sugar-sweetened beverages contributed to more than 21% of all new diabetes cases. In Latin America and the Caribbean, they contributed to nearly 24% of new diabetes cases and more than 11% of new cases of cardiovascular disease.

Colombia, Mexico, and South Africa are countries that have been particularly hard hit.  More than 48% of all new diabetes cases in Colombia were attributable to consumption of sugary drinks. Nearly one third of all new diabetes cases in Mexico were linked to sugary drink consumption. In South Africa, 27.6% of new diabetes cases and 14.6% of cardiovascular disease cases were attributable to sugary drink consumption.

Sugary beverages are rapidly digested, causing a spike in blood sugar levels with little nutritional value. Regular consumption over time leads to weight gain, insulin resistance, and a host of metabolic issues tied to type 2 diabetes and heart disease, two of the world’s leading causes of death.

“Sugar-sweetened beverages are heavily marketed and sold in low- and middle-income nations. Not only are these communities consuming harmful products, but they are also often less well equipped to deal with the long-term health consequences,” says Dariush Mozaffarian, senior author on the paper and director of the Food is Medicine Institute at the Friedman School.

As countries develop and incomes rise, sugary drinks become more accessible and desirable, the authors say. Men are more likely than women to suffer the consequences of sugary drink consumption, as are younger adults compared to their older counterparts, the researchers say.

“We need urgent, evidence-based interventions to curb consumption of sugar-sweetened beverages globally, before even more lives are shortened by their effects on diabetes and heart disease,” says Laura Lara-Castor, NG24, first author on the paper who earned her PhD at the Friedman School and is now at the University of Washington.

The study’s authors call for a multi-pronged approach, including public health campaigns, regulation of sugary drink advertising, and taxes on sugar-sweetened beverages.  Some countries have already taken steps in this direction. Mexico, which has one of the highest per capita rates of sugary drink consumption in the world, introduced a tax on the beverages in 2014. Early evidence suggests that the tax has been effective in reducing consumption, particularly among lower-income individuals. 

“Much more needs to be done, especially in countries in Latin America and Africa where consumption is high and the health consequence severe,” says Mozaffarian. “As a species, we need to address sugar-sweetened beverage consumption.”

Source: Tufts University

Categories : New Compounds and TreatmentsTags : Leave a comment

New Drug Shows Promise against Duchenne Muscular Dystrophy

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Photo by Jon Tyson on Unsplash

A novel drug holds promise for treating Duchenne muscular dystrophy (DMD), a rare genetic disorder that causes severe muscle degeneration.

McGill University researchers have discovered that an experimental compound called K884 can boost the natural repair abilities of muscle stem cells. Current treatments can slow muscle damage, but don’t address the root problem.

DMD affects about one in 5000 boys worldwide, often leading to wheelchair dependence by the teenage years and life-threatening complications in early adulthood.

“By strengthening muscle repair rather than just slowing degeneration, therapies that stimulate muscle stem cell function have the potential to improve quality of life for DMD patients. It may help restore muscle function and, ultimately, offer greater independence,” said senior author Natasha Chang, Assistant Professor in McGill’s Department of Biochemistry.

Building stronger muscles from stem cells

Biotechnology company Kanyr Pharma originally developed the drug for cancer and metabolic diseases, but it has not yet been approved for any specific use. This preclinical study marks the first time the drug has been tested in DMD cells.

The researchers put DMD-affected muscle stem cells from humans and mice under the microscope to see how they responded to the drug. They observed that experimental drug blocks specific enzymes, allowing muscle stem cells to develop into functional muscle tissue.

“What makes K884 particularly promising is its precision. It targets DMD-affected cells without affecting healthy muscle stem cells,” said Chang.

Unlike gene therapy, which targets specific genetic mutations and isn’t suitable for all patients, K884 works at the cellular level, restoring muscle repair regardless of the mutation causing the disease. This makes it a potential treatment option for all DMD patients, she added.

A new understanding of DMD

The findings, published in Life Science Alliance, add to a growing body of evidence that challenges previous assumptions about DMD’s root cause.

“This disease has historically been seen as a muscle problem caused by a missing protein called dystrophin,” said Chang. “But new research, including our own, shows that restoring stem cell function is just as critical for repairing muscle.”

The team plans to keep testing the drug, focusing on its safety and long-term effects, while also exploring other related compounds, some of which are already involved in early human trials.

Source: McGill University