Posted on Alzheimer's, Multiple Sclerosis

How Brain Inflammation (in MS) Affects Behavior in Men and Women Differently

An Australian-first study has lifted the lid on how couples living with rheumatoid arthritis cope with the debilitating disease finding that those who cope with problems together had less psychological distress and better relationships.

For people with multiple sclerosis (MS), understanding how brain inflammation impacts behavior can provide insight into some of the common symptoms they experience. New research from the University of Technology Sydney (UTS) sheds light on how inflammation in the hippocampus—a part of the brain critical for memory and emotions—affects motivation and behavior, with clear differences between males and females.

What’s the Connection Between Brain Inflammation and Behavior?

The hippocampus is central to memory, learning, and emotional regulation, but it’s also affected by inflammation in diseases like MS, Alzheimer’s, and depression. This inflammation, called neuroinflammation, often results in symptoms like:

  • Apathy
  • Struggles with daily activities
  • Changes in food preferences

Interestingly, these symptoms tend to be more severe in women than in men.

“While inflammation in the hippocampus isn’t the sole reason for behavior changes, it likely sets off a chain reaction in the brain that influences how we think and act,” explained Dr. Laura Bradfield, Director of the Brain and Behaviour Lab at UTS.

What Did the Study Find?

Using mice, researchers at UTS simulated neuroinflammation by introducing a bacterial toxin called lipopolysaccharide into the hippocampus. This toxin triggers an immune response in the brain, mimicking the inflammation seen in diseases like MS.

The findings were fascinating:

  • In both male and female mice, activity and movement levels increased.
  • Females showed more significant changes in food-seeking behaviour, suggesting inflammation affects their motivation differently.

The research also highlighted the role of microglia and astrocytes, two types of brain cells that interact with neurons during inflammation, showing how complex these changes are at a cellular level.

Why Do Women Experience Stronger Effects?

The study suggests that hormones like estrogen might play a role in how neuroinflammation affects the brain. These sex-specific differences could explain why women with MS often experience more severe cognitive and behavioural symptoms.

What Does This Mean for MS Patients?

For those living with MS, this research offers hope for more personalized treatments. By targeting hippocampal neuroinflammation, future therapies might alleviate symptoms like memory issues, apathy, and difficulty with daily tasks—potentially improving brain health, especially for women.

“These findings open the door to developing treatments that consider how men and women respond differently to brain inflammation,” said Dr. Kiruthika Ganesan, the study’s lead author.

What’s Next?

The researchers are calling for more studies to understand:

  • How hormones influence these sex-specific effects.
  • The long-term impact of neuroinflammation on brain health.

For now, the study serves as a reminder of how critical it is to consider sex-specific differences in developing therapies for MS and other neurological conditions.

By tailoring treatments to these differences, there’s potential to not only reduce symptoms but also improve overall quality of life for people with MS.

4o

Posted on Multiple Sclerosis

How Do MS Drugs Affect Pregnancy?

New guidelines for pregnancy in multiple sclerosis
Pregnancy can be a complex journey for women with multiple sclerosis (MS), especially when considering the impact of disease-modifying therapies (DMTs). A groundbreaking study from Ruhr-University Bochum offers one of the largest datasets yet to understand the effects of these medications during pregnancy.
What the Study Looked At

The study analyzed 2,885 pregnancies from the German Multiple Sclerosis and Pregnancy Registry, spanning data collected between 2006 and 2023. It examined women exposed to a variety of DMTs, including:
Interferons
Glatiramer acetate
Dimethyl fumarate
Teriflunomide
S1P modulators (like fingolimod and ponesimod)
Alemtuzumab
Natalizumab
Anti-CD20 antibodies (rituximab, ocrelizumab, ofatumumab)
Cladribine
For comparison, the study also included 837 women with MS who didn’t take any MS medication during pregnancy.

Key Findings
No Major Increase in Pregnancy Risks
Most DMTs did not significantly increase the risk of complications like spontaneous abortions, premature births, or major birth defects.
However, the data for medications like cladribine, teriflunomide, and alemtuzumab was limited, making it harder to draw firm conclusions about rare complications, such as severe infections or birth defects.
Low Birth Weight Was a Concern
Babies born to mothers with MS—whether or not they took DMTs—were more likely to have a lower-than-average birth weight.
18.8% of babies in the study had low birth weight compared to 10% nationally in Germany.
The risk was highest with S1P modulators (27.4%) and anti-CD20 antibodies (24.1%).
Low birth weight is a concern because it can lead to complications, including neonatal death and long-term health risks like type 2 diabetes and cardiovascular disease.
Infections Were Rare but Monitored
Serious infections were infrequent, but:
Fumarate (2.8%) and alemtuzumab (9.1%) were linked to more infections during pregnancy.
Severe infections were slightly higher in cases treated with natalizumab in late pregnancy (3%) or S1P modulators (3%).
Anti-CD20 therapies, surprisingly, were associated with a lower rate of severe infections (0.6%) than expected.
Women exposed to natalizumab or anti-CD20 antibodies were more likely to need antibiotics during pregnancy.
What Does This Mean for Pregnant Women with MS?
While the findings are reassuring overall, they underscore the importance of an individual risk-benefit assessment when deciding whether to continue MS medications during pregnancy.
Monitoring is Key: Pregnant women with MS should work closely with their healthcare providers to ensure their treatment plan balances managing their MS symptoms with minimizing potential risks to the baby.
More Research Needed: The registry will continue tracking outcomes to see if babies with low birth weight eventually catch up in growth.
Conclusion
The study offers valuable insights into how MS medications interact with pregnancy. While most DMTs don’t pose a significant risk, some may influence birth weight or infection risk, emphasizing the need for personalized care and close medical supervision.


4o



Posted on Diabetes

Metformin’s “Secret Sauce” Revealed: How This Wonder Drug Works

Pipetting liquified metformin

First study author Colleen Reczek pipettes liquified metformin. Credit Northwestern University

Metformin, a diabetes drug taken by millions, has long been hailed as a “wonder drug.” Not only does it lower blood sugar for people with Type 2 diabetes, but it’s also been shown to slow cancer growth, reduce inflammation, and even improve COVID-19 outcomes. Despite its widespread use for over 60 years, scientists have never fully understood how metformin works — until now.

In a groundbreaking study published in Science Advances, researchers at Northwestern University have finally cracked the code. They’ve discovered that metformin targets the mitochondria, the energy powerhouses of our cells, to lower blood sugar.

The Mitochondria Connection

Metformin specifically interferes with mitochondrial complex I, a key component of the cell’s energy-making machinery. By doing so, it temporarily disrupts the cell’s energy supply in a way that lowers glucose levels. Importantly, this disruption primarily affects cells in the gut, liver, and kidneys — areas where metformin’s effects are most needed — while leaving healthy cells largely untouched.

“This research gives us a clearer understanding of how metformin works,” said Navdeep Chandel, senior author of the study and a professor at Northwestern University Feinberg School of Medicine. “It’s a mystery we’ve been trying to solve for decades.”

Testing the Theory in Mice

To confirm their findings, the research team created genetically engineered mice with a yeast enzyme (NDI1) that mimics mitochondrial complex I but is resistant to metformin’s effects. When treated with metformin, the blood sugar levels in normal mice dropped, but those in the NDI1-engineered mice didn’t budge. This experiment proved that mitochondrial complex I is a key target of metformin in lowering glucose levels.

While the study showed that metformin primarily works through mitochondrial complex I, researchers noted it might also act on other pathways to a more minor degree, leaving room for future exploration.

Beyond Diabetes: Metformin’s Many Superpowers

Metformin’s effects aren’t limited to diabetes. Previous research from Chandel’s team revealed that the drug’s anti-cancer properties are also linked to its ability to inhibit mitochondrial complex I. Another study by co-author Dr. Scott Budinger found that metformin reduces inflammation caused by pollution exposure.

“We think that metformin’s diverse benefits — from lowering blood sugar to reducing inflammation and possibly fighting cancer — all tie back to its inhibition of mitochondrial complex I,” Chandel explained.

A Glimpse Into the Future

Metformin’s discovery as a mitochondrial disruptor could pave the way for new treatments targeting mitochondrial complex I. It might even explain how metformin improves healthspan (the length of time people live in good health).

While this research brings us closer to understanding metformin’s “secret sauce,” Chandel emphasizes that more studies are needed to confirm and expand on these findings.

This humble drug, derived from the French lilac plant, continues to cement its status as a medical marvel, offering hope not just for diabetes patients but for a broader range of health challenges.

As science digs deeper into metformin’s mechanisms, one thing is clear: this 60-year-old drug still has plenty of surprises.

Posted on Autism

New Genetic Discovery Sheds Light on Autism

DNA and autism
DNA and autism

Researchers have uncovered a new genetic link to autism, offering fresh insights into why the condition is more common in males. The breakthrough, detailed in The American Journal of Human Genetics, identifies variants in the DDX53 gene, located on the X chromosome, as key contributors to autism. This finding provides a deeper understanding of the biological mechanisms behind autism and could improve diagnosis and treatment.

A Genetic Clue to Male Prevalence

Autism affects more males than females, and this new study helps explain why. Researchers at The Hospital for Sick Children (SickKids) in Canada, in collaboration with the Istituto Giannina Gaslini in Italy, analyzed families with autistic members. They discovered that specific variants in the DDX53 gene were maternally inherited in individuals with autism—most of whom were male.

“By pinpointing DDX53 as a key player, particularly in males, we can better understand the biological mechanisms at play and improve diagnostic accuracy for individuals and their families,” says Dr. Stephen Scherer, Senior Scientist at SickKids and a lead researcher in the study.

The DDX53 gene is involved in brain development and function but had not previously been linked to autism. Another gene nearby, PTCHD1-AS, also showed potential involvement. For example, one boy and his mother, both autistic with minimal support needs, had a genetic deletion that included parts of DDX53 and PTCHD1-AS.

International Collaboration Strengthens Findings

This discovery resulted from a global effort involving institutions in Canada, Italy, and the United States. Using databases like Autism Speaks’ MSSNG and the Simons Foundation Autism Research Initiative, researchers identified 26 more individuals with similar DDX53 variants, strengthening the evidence for its role in autism.

Lead author Dr. Marcello Scala, from the Istituto Giannina Gaslini, highlighted the importance of this discovery:
“This gene has long eluded us. Linking DDX53 to autism not only advances clinical genetic testing but also opens up new areas of research into the behavioural traits associated with autism.”

The Bigger Picture: The Role of the X Chromosome

In a related study published alongside this one, Scherer and his team identified 59 genetic variants on the X chromosome-linked to autism. These included DMD, HDAC8, and FGF13, among others. Importantly, some of these genes, like FGF13, show sex-specific differences, further emphasizing the role of the X chromosome in autism’s male predominance.

“These findings provide new insights into the biology of the X chromosome in autism,” says Scherer. “They suggest that certain genes, such as DDX53 and FGF13, should be explored further.”

Rethinking Autism Research

Interestingly, the study points out a challenge in current research models: DDX53 does not have an equivalent gene in commonly used lab animals like mice. This means researchers must rethink how they study autism in the lab.

“Insights from this study could significantly influence the design and interpretation of autism research, particularly in developing new models,” Scherer adds.

Hope for Families

These findings could pave the way for more precise diagnostic tools and treatments for autism, bringing hope to millions of families worldwide. Scherer emphasizes the importance of these discoveries:
“Both studies provide even more evidence that complex neurobehavioral conditions like autism can sometimes have simple biological underpinnings.”

By identifying key genetic factors like DDX53, researchers are not only unraveling the mysteries of autism but also laying the groundwork for more effective support for autistic individuals and their families.

Posted on Autism

Autism: A Global Health Challenge Affecting Millions

Vast under-treatment of diabetes seen in global study

A recent global study has shed light on the significant impact of autism, revealing that an estimated 61.8 million people worldwide were autistic in 2021. This equates to 1 in every 127 individuals. Conducted as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021, the analysis highlights autism as one of the top ten contributors to non-fatal health burdens among youth under 20.

Key Findings: Disparities in Prevalence

The study highlights essential disparities in autism prevalence based on sex and region:

  • Sex Differences: Autism is nearly twice as prevalent in males, with 1,065 cases per 100,000 males globally, compared to 508 per 100,000 females.
  • Regional Variations: High-income Asia Pacific countries, such as Japan, have the highest prevalence at 1,560 cases per 100,000 people. In contrast, Tropical Latin America and Bangladesh report the lowest prevalence rates.

Despite these differences, autism is a universal condition affecting people across all age groups and regions. Rising rates of disability-adjusted life years (DALYs) associated with autism are closely linked to global population growth.

Urgent Need for Action

The findings underscore the importance of early detection and sustained support for autistic individuals and their caregivers. Key areas for improvement include:

  • Early Detection and Diagnosis: Enhanced diagnostic tools are vital, especially for adults and individuals in low- and middle-income countries where access to care is often limited.
  • Lifelong Support Services: Autism requires tailored interventions that adapt to the needs of individuals throughout their lives, encompassing education, employment, and independent living.
  • Caregiver Support: Families and caregivers often face significant challenges; resources and programs to alleviate their burden are essential.
  • Addressing Comorbidities: Targeted efforts to mitigate risks such as suicide and other health complications can improve overall outcomes.

Policy Implications

This research provides a strong foundation for shaping global policies to improve the quality of life for autistic individuals. Expanding geographic data coverage will help refine interventions while prioritizing funding for autism-focused initiatives can bridge gaps in care and access. By addressing these challenges, governments, healthcare systems, and communities can better support the millions of autistic people worldwide.

In conclusion, autism remains a pressing global health challenge, demanding coordinated action to ensure that all individuals can achieve their fullest potential. Early detection, inclusive services, and compassionate support are key to transforming outcomes and improving lives.