Category: Neurodegenerative Diseases

Categories : Neurodegenerative Diseases New Compounds and TreatmentsTags :

Royalty-based Method Offers New Model for ALS Drug Development

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A team of researchers from the MIT Sloan School of Management, the Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital (MGH), Questrom School of Business at Boston University, and QLS Advisors have introduced a new approach to funding clinical trials for amyotrophic lateral sclerosis (ALS) therapies. The study, “Financing Drug Development via Adaptive Platform Trials,” published today in PLOS One, outlines a financing model that merges the efficiencies of adaptive platform trials — lower costs and shorter durations — with an innovative, royalty-based investment structure designed to accelerate therapeutic development for ALS and other serious diseases.

ALS — also often called Lou Gehrig’s disease — is a progressive, neurodegenerative disease with no cure. Despite its devastating impact, the pace of new therapy development has remained sluggish—largely due to the high cost, duration, and risks associated with traditional clinical trials. This bottleneck has often discouraged conventional investors, leaving promising research to languish.

To tackle this challenge, the authors propose an investment fund that finances half the cost of an adaptive platform trial in exchange for future royalties from successful drugs that emerge from the trial. Adaptive platform trials allow multiple drug candidates to be tested simultaneously under a single master protocol, and results are interpreted on a real-time basis to determine efficacy or futility. Drawing on data from the HEALEY ALS Platform Trial administered by the Healey & AMG Center for ALS at MGH, and realistic assumptions, their simulated fund generated an expected return of 28%, with a 22% probability of total loss, which may be attractive to more risk-tolerant and impact-driven investors such as hedge funds, sovereign wealth funds, family offices, and philanthropists. Their findings suggest that generating returns more palatable for mainstream investors could be achieved by funding multiple platform trials simultaneously and by employing financial tools such as securitization — a method that bundles future income from assets like loans or royalties into investment products.

“ALS clinical trials face significant hurdles — from high costs and long timelines to limited funding pools,” said Merit E. Cudkowicz, MD, MSC, Executive Director at Mass General Brigham Neuroscience Institute and Director of the Healey & AMG Center for ALS. “Our platform trial model has already shown that we can test more therapies more efficiently. What’s still missing is sustainable financing. This novel approach could be a game-changer, enabling us to launch trials faster, include more promising therapies, and bring us closer to our shared goal: delivering effective treatments to people with ALS as quickly as possible.”

While their study focused on ALS, the authors believe such a funding model could be applied to other disease areas as well, especially those with well-defined endpoints, where treatment success can be measured clearly and reliably.

Source: Mass General Brigham

Categories : Neurodegenerative DiseasesTags :

Mitochondrial Failure Contributes to Neuron Death in Multiple Sclerosis

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This is a pseudo-colored image of high-resolution gradient-echo MRI scan of a fixed cerebral hemisphere from a person with multiple sclerosis. Credit: Govind Bhagavatheeshwaran, Daniel Reich, National Institute of Neurological Disorders and Stroke, National Institutes of Health

Multiple sclerosis (MS) affects some 2.3 million people worldwide, with 80% experiencing inflammation in the cerebellum, a brain region crucial for movement and balance. This inflammation can lead to tremors, poor coordination, and motor control issues, which often worsen over time due to the loss of healthy brain tissue.

Researchers at the University of California, Riverside, have made a significant discovery about the underlying mechanisms of cerebellar degeneration in MS. Their study, published in PNAS, suggests that mitochondrial dysfunction may play a key role in the progressive loss of Purkinje cells and worsening motor impairments.

Purkinje cells are essential for coordinating smooth movements and balance. In MS, these cells can be damaged, leading to problems with coordination and movement, known as ataxia. The study found that Purkinje cells in MS patients had fewer branches, lost myelin, and experienced mitochondrial problems, resulting in a failing energy supply.

“Our study, conducted by my graduate student Kelley Atkinson, proposes that inflammation and demyelination in the cerebellum disrupt mitochondrial function, contributing to nerve damage and Purkinje cell loss,” said Seema Tiwari-Woodruff, a professor of biomedical sciences in the UC Riverside School of Medicine, who led the research team. “We observed a significant loss of the mitochondrial protein COXIV in demyelinated Purkinje cells, suggesting that mitochondrial impairment contributes directly to cell death and cerebellar damage.”

The research team used a mouse model of MS to investigate mitochondrial alterations during disease progression. They found that the mice lost Purkinje cells over time, similar to people with MS. The loss of energy seemed to be a key part of MS, with cells only dying later.

“Our research looked at brain tissue from MS patients and found major issues in these neurons: they had fewer branches, were losing myelin, and had mitochondrial problems – meaning their energy supply was failing,” Tiwari-Woodruff said. “Because Purkinje cells play such a central role in movement, their loss can cause serious mobility issues. Understanding why they’re damaged in MS could help us find better treatments to protect movement and balance in people with the disease.”

The study suggests that targeting mitochondrial health may be a promising strategy to slow or prevent neurological decline and improve quality of life for people living with MS.

The researchers plan to further investigate whether mitochondrial impairment affects other brain cells, such as oligodendrocytes and astrocytes. This research has the potential to open the door to finding ways to protect the brain early on, such as boosting energy in brain cells or aiding repair of the myelin sheaths.

Source: University of California, Riverside

Categories : Neurodegenerative Diseases VaccinesTags :

RSV Vaccine Reduces the Risk of Dementia, New Research Shows

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A new study by the University of Oxford, published in the journal npj Vaccines, shows that a vaccine against respiratory syncytial virus (RSV) is associated with a 29% reduction in dementia risk in the following 18 months. The findings suggest a novel explanation for how vaccines produce this effect.

Recent studies have shown convincingly that vaccines against shingles (Herpes zoster) reduce the risk of dementia. The shingles vaccine now in widespread use (Shingrix) has more of an effect than the previous one (Zostavax). A key difference between these vaccines is that Shingrix contains an ‘adjuvant’, an ingredient designed to enhance the vaccine’s effect. It is therefore possible that the adjuvant contributes to Shingrix’ greater effect than Zostavax on reducing dementia.

The new study, supported by the National Institute for Health and Care Research (NIHR) Oxford Health Biomedical Research Centre (OH BRC), supports this possibility. Researchers analysed the health records of over 430 000 people in the USA in the TriNetX network. They found that the Arexvy vaccine – which protects against respiratory syncytial virus (RSV), a common virus that causes cold-like symptoms – was also linked to a significantly lower risk of developing dementia. Arexvy, now offered to adults over 60, contains the same adjuvant as Shingrix. Both vaccines were similarly effective in reducing dementia risk compared to the flu vaccine (which does not contain the adjuvant); in the 18 months following receipt of Arexvy there was a 29% reduction in diagnoses of dementia. These findings held true across a range of additional analyses and were similar in men and women.

It is not clear how the adjuvant, called AS01, might help lower the risk of dementia. However, laboratory studies show that AS01 stimulates cells of the immune system that could help protect the brain from some of the harmful processes underlying dementia. These benefits of the adjuvant in reducing dementia risk could be in addition to the protection that comes from preventing infections like shingles and RSV themselves.

It is not yet known whether these vaccines prevent dementia or, more likely, delay its onset. Either way, the effect is significant, especially given that no other treatments are known that delay or prevent the condition.

The likely beneficial effect on dementia risk is in addition to the vaccines’ proven ability to prevent shingles and RSV, both of which are unpleasant and sometimes serious illnesses.

Lead author, Associate Professor Maxime Taquet, NIHR Academic Clinical Lecturer, Department of Psychiatry, University of Oxford, said: “Our findings show that vaccines against two separate viruses, shingles and RSV, both lead to reductions in dementia. This gives another reason to have the vaccines, in addition to their effectiveness at preventing these serious illnesses.’

Senior author, Professor Paul Harrison, Department of Psychiatry, University of Oxford and Co-Lead for the Molecular Targets theme in OH BRC, said: ‘The findings are striking. We need studies to confirm whether the adjuvant present in some vaccines contributes to the reduced dementia risk, and to understand how it does so.’

Source: Oxford University

Categories : Cancer Neurodegenerative DiseasesTags :

Breast Cancer Treatment Linked to a Reduction in Alzheimer’s Disease Risk

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A Korean population-based cohort study investigated the risk of Alzheimer’s disease (AD) among breast cancer survivors compared to age-matched controls without cancer. The study, published in JAMA Network Open, found that breast cancer survivors had an 8% lower risk of AD than controls, with a significant association in survivors over 65 years old – though the effect did not persist past five years. Radiotherapy was associated with a lower risk of AD among breast cancer survivors – but not other treatments.

Breast cancer survivors may experience long-term health consequences, including cognitive function and risk of dementia. The risk of AD among breast cancer survivors is still unclear and may vary depending on age at diagnosis, treatment received, and time since treatment.

Previous studies reported mixed results on the risk of AD among breast cancer survivors, with some finding no increase in risk and others finding a 35% increased risk for those diagnosed at age 65 or older. These studies have been hampered by a number of methodological issues, including not accounting for risk factors.

Cytotoxic chemotherapy can cause cognitive decline termed ‘chemobrain’. Other chemotherapy drugs such as anthracycline may reduced AD risk by reducing the formation of amyloid deposits. Endocrine therapy may increase the risk of dementia by lowering oestrogen, but studies suggest that the use of tamoxifen and aromatase inhibitors is associated with a lower risk of AD. An increase in dementia is seen in radiotherapy for head and neck cancers.

To investigate the risk of AD among breast cancer survivors, researchers used the Korean National Health Insurance Service (K-NHIS) database, exploring whether there is an association with cancer treatment and various confounding factors.

Among 70 701 breast cancer survivors (mean age, 53.1 years), 1229 cases of AD were detected, with an incidence rate of 2.45 per 1000 person-years. Survivors exhibited a slightly lower risk of AD compared with cancer-free controls, especially among individuals 65 years or older (SHR, 0.92; 95% CI, 0.85-0.99). But landmark analyses found that this lower risk did not persist beyond five years of survival. Radiotherapy was associated with reduced risk of AD among survivors, while chemotherapy and endocrine therapy had no significant impact. Anthracycline use, however, did show a non-significant decrease in risk.

Differences in doses and timing of radiotherapy may influence the effects. The incident exposure to the brain is estimated to be 0.2Gy from a breast cancer radiotherapy dose of 50Gy. A pilot study found that patients with AD who received low-dose whole-brain radiotherapy at 3Gy showed a temporary improvement in cognitive function. This improvement is believed to be due to a neuroprotective effect on microglia. Other studies have noted a transient risk reduction for AD in breast cancer radiotherapy; however, patients receiving radiotherapy usually do so in conjunction with breast-conserving surgery – those opting for this procedure are younger, with fewer comorbidities and smaller tumours.

The study suggests that cancer treatment may have benefits against AD development, but the risk of AD may differ depending on the duration of survival.

The findings indicate that breast cancer treatment may not directly lead to AD, and that managing modifiable risk factors for AD, such as smoking and diabetes, is a feasible option to lower AD risk among breast cancer survivors.

Categories : Genetics Neurodegenerative DiseasesTags :

Iron Plays a Major Role in Down Syndrome-Associated Alzheimer’s Disease

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New USC research indicates how iron-related oxidative damage and cell death may hasten the development of Alzheimer’s disease in people with Down syndrome

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Scientists at the University of Southern Carolina have discovered a key connection between high levels of iron in the brain and increased cell damage in people who have both Down syndrome and Alzheimer’s disease.

In the study, researchers found that the brains of people diagnosed with Down syndrome and Alzheimer’s disease (DSAD) had twice as much iron and more signs of oxidative damage in cell membranes compared to the brains of individuals with Alzheimer’s disease alone or those with neither diagnosis. The results, published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, point to a specific cellular death process that is mediated by iron, and the findings may help explain why Alzheimer’s symptoms often appear earlier and more severely in individuals with Down syndrome.

“This is a major clue that helps explain the unique and early changes we see in the brains of people with Down syndrome who develop Alzheimer’s,” said Max Thorwald, lead author of the study and a postdoctoral fellow in the laboratory of University Professor Emeritus Caleb Finch at the USC Leonard Davis School. “We’ve known for a long time that people with Down syndrome are more likely to develop Alzheimer’s disease, but now we’re beginning to understand how increased iron in the brain might be making things worse.”

Down syndrome and Alzheimer’s

Down syndrome is caused by having an extra third copy, or trisomy, of chromosome 21. This chromosome includes the gene for amyloid precursor protein, or APP, which is involved in the production of amyloid-beta (Aβ), the sticky protein that forms telltale plaques in the brains of people with Alzheimer’s disease.

Because people with Down syndrome have three copies of the APP gene instead of two, they tend to produce more of this protein. By the age of 60, about half of all people with Down syndrome show signs of Alzheimer’s disease, which is approximately 20 years earlier than in the general population.

“This makes understanding the biology of Down syndrome incredibly important for Alzheimer’s research,” said Finch, the study’s senior author.

Key findings point to ferroptosis

The research team studied donated brain tissue from individuals with Alzheimer’s, DSAD, and those without either diagnosis. They focused on the prefrontal cortex — an area of the brain involved in thinking, planning, and memory — and made several important discoveries:

  • Iron levels much higher in DSAD brains: Compared to the other groups, DSAD brains had twice the amount of iron in the prefrontal cortex. Scientists believe this buildup comes from tiny brain blood vessel leaks called microbleeds, which occur more frequently in DSAD than in Alzheimer’s and are correlated with higher amounts of APP.
  • More damage to lipid-rich cell membranes: Cell membranes are made of fatty compounds called lipids and can be easily damaged by chemical stress. In DSAD brains, the team found more byproducts of this type of damage, known as lipid peroxidation, compared to amounts in Alzheimer’s-only or control brains.
  • Weakened antioxidant defense systems: The team found that the activity of several key enzymes that protect the brain from oxidative damage and repair cell membranes was lower in DSAD brains, especially in areas of the cell membrane called lipid rafts.

Together, these findings indicate increased ferroptosis, a type of cell death characterised by iron-dependent lipid peroxidation, Thorwald explained: “Essentially, iron builds up, drives the oxidation that damages cell membranes, and overwhelms the cell’s ability to protect itself.”

Lipid rafts: a hotspot for brain changes

The researchers paid close attention to lipid rafts — tiny parts of the brain cell membrane that play crucial roles in cell signalling and regulate how proteins like APP are processed. They found that in DSAD brains, lipid rafts had much more oxidative damage and fewer protective enzymes compared to Alzheimer’s or healthy brains.

Notably, these lipid rafts also showed increased activity of the enzyme β-secretase, which interacts with APP to produce Aβ proteins. The combination of more damage and more Aβ production may promote the growth of amyloid plaques, thus speeding up Alzheimer’s progression in people with Down syndrome, Finch explained.

Rare Down syndrome variants offer insight

The researchers also studied rare cases of individuals with “mosaic” or “partial” Down syndrome, in which the third copy of chromosome 21 is only present in a smaller subset of the body’s cells. These individuals had lower levels of APP and iron in their brains and tended to live longer. In contrast, people with full trisomy 21 and DSAD had shorter lifespans and higher levels of brain damage.

“These cases really support the idea that the amount of APP — and the iron that comes with it — matters a lot in how the disease progresses,” Finch said.

Looking ahead

The team says their findings could help guide future treatments, especially for people with Down syndrome who are at high risk of Alzheimer’s. Early research in mice suggests that iron-chelating treatments, in which medicine binds to the metal ions and allows them to leave the body, may reduce indicators of Alzheimer’s pathology, Thorwald noted.

“Medications that remove iron from the brain or help strengthen antioxidant systems might offer new hope,” Thorwald said. “We’re now seeing how important it is to treat not just the amyloid plaques themselves but also the factors that may be hastening the development of those plaques.”

Source: University of Southern California

Categories : Exercise Neurodegenerative DiseasesTags :

Exercise Activates Cells that Protect Against Alzheimer’s

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Using advanced single-nuclei RNA sequencing (snRNA-seq) and a widely used preclinical model for Alzheimer’s disease, researchers from Mass General Brigham and collaborators at SUNY Upstate Medical University have identified specific brain cell types that responded most to exercise. These findings, which were validated in samples from humans, shed light on the connection between exercise and brain health and point to future drug targets. Results are published in Nature Neuroscience.

“While we’ve long known that exercise helps protect the brain, we didn’t fully understand which cells were responsible or how it worked at a molecular level,” said senior author Christiane Wrann, DVM, PhD, a neuroscientist at Massachusetts General Hospital. “Now, we have a detailed map of how exercise impacts each major cell type in the memory centre of the brain in Alzheimer’s disease.”

Brain support cells—astrocytes enriched in the protein cadherin-4 (CDH4)
Scientists identified a distinct subtype of brain support cells—astrocytes enriched in the protein cadherin-4 (CDH4), shown in magenta, that seem to protect nerve cells against cell death. In Alzheimer’s disease, these cells become less abundant, but exercise seems to strengthen them. (Image credit: Luis Moreira)

The study focused on a part of the hippocampus – a critical region for memory and learning that is damaged early in Alzheimer’s disease. The research team leveraged single-nuclei RNA sequencing, a relatively new technologies that allow researchers to look at activity at the molecular level in single cells for an in-depth understanding of diseases like Alzheimer’s.

The researchers exercised a common mouse model for Alzheimer’s disease using running wheels, which improved their memory compared to the sedentary counterparts. They then analysed gene activity across thousands of individual brain cells, finding that exercise changed activity both in microglia, a disease-associated population of brain cells, and in a specific type of neurovascular-associated astrocyte (NVA), newly discovered by the team, which are cells associated with blood vessels in the brain. Furthermore, the scientist identified the metabolic gene Atpif1 as an important regulator to create new neurons in the brain. “That we were able to modulate newborn neurons using our new target genes set underscores the promise our study,” said lead author Joana Da Rocha, PhD, a postdoctoral fellow working in Dr Wrann’s lab.

To ensure the findings were relevant to humans, the team validated their discoveries in a large dataset of human Alzheimer’s brain tissue, finding striking similarities.

“This work not only sheds light on how exercise benefits the brain but also uncovers potential cell-specific targets for future Alzheimer’s therapies,” said Nathan Tucker, a biostatistician at SUNY Upstate Medical University and co-senior of the study. “Our study offers a valuable resource for the scientific community investigating Alzheimer’s prevention and treatment.”

Source: Mass General Brigham

Categories : Implants and Prostheses Neurodegenerative DiseasesTags :

First-of-its-kind Technology Helps Man with ALS ‘Speak’ in Real Time

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An investigational brain-computer interface (BCI) allows the study participant to communicate through a computer. Credit: UC Davis

Researchers at the University of California, Davis, have developed an investigational brain-computer interface that holds promise for restoring the ability to hold real-time conversations to people who have lost the ability to speak due to neurological conditions.

In a new study published in the scientific journal Nature, the researchers demonstrate how this new technology can instantaneously translate brain activity into voice as a person tries to speak – effectively creating a digital vocal tract with no detectable delay.

The system allowed the study participant, who has amyotrophic lateral sclerosis (ALS), to “speak” through a computer with his family in real time, change his intonation and “sing” simple melodies.

“Translating neural activity into text, which is how our previous speech brain-computer interface works, is akin to text messaging. It’s a big improvement compared to standard assistive technologies, but it still leads to delayed conversation. By comparison, this new real-time voice synthesis is more like a voice call,” said Sergey Stavisky, senior author of the paper and an assistant professor in the UC Davis Department of Neurological Surgery. Stavisky co-directs the UC Davis Neuroprosthetics Lab.

“With instantaneous voice synthesis, neuroprosthesis users will be able to be more included in a conversation. For example, they can interrupt, and people are less likely to interrupt them accidentally,” Stavisky said.

Decoding brain signals at heart of new technology

The man is enrolled in the BrainGate2 clinical trial at UC Davis Health. His ability to communicate through a computer has been made possible with an investigational brain-computer interface (BCI). It consists of four microelectrode arrays surgically implanted into the region of the brain responsible for producing speech.

These devices record the activity of neurons in the brain and send it to computers that interpret the signals to reconstruct voice.

“The main barrier to synthesising voice in real-time was not knowing exactly when and how the person with speech loss is trying to speak,” said Maitreyee Wairagkar, first author of the study and project scientist in the Neuroprosthetics Lab at UC Davis. “Our algorithms map neural activity to intended sounds at each moment of time. This makes it possible to synthesise nuances in speech and give the participant control over the cadence of his BCI-voice.”

Instantaneous, expressive speech with BCI shows promise

The brain-computer interface was able to translate the study participant’s neural signals into audible speech played through a speaker very quickly – one-fortieth of a second. This short delay is similar to the delay a person experiences when they speak and hear the sound of their own voice.

The technology also allowed the participant to say new words (words not already known to the system) and to make interjections. He was able to modulate the intonation of his generated computer voice to ask a question or emphasize specific words in a sentence.

The participant also took steps toward varying pitch by singing simple, short melodies.

His BCI-synthesized voice was often intelligible: Listeners could understand almost 60% of the synthesized words correctly (as opposed to 4% when he was not using the BCI).

Real-time speech helped by algorithms

The process of instantaneously translating brain activity into synthesized speech is helped by advanced artificial intelligence algorithms.

The algorithms for the new system were trained with data collected while the participant was asked to try to speak sentences shown to him on a computer screen. This gave the researchers information about what he was trying to say.

The electrodes measured the firing patterns of hundreds of neurons. The researchers aligned those patterns with the speech sounds the participant was trying to produce at that moment in time. This helped the algorithm learn to accurately reconstruct the participant’s voice from just his neural signals.

Clinical trial offers hope

“Our voice is part of what makes us who we are. Losing the ability to speak is devastating for people living with neurological conditions,” said David Brandman, co-director of the UC Davis Neuroprosthetics Lab and the neurosurgeon who performed the participant’s implant.

“The results of this research provide hope for people who want to talk but can’t. We showed how a paralyzed man was empowered to speak with a synthesized version of his voice. This kind of technology could be transformative for people living with paralysis.”

Brandman is an assistant professor in the Department of Neurological Surgery and is the site-responsible principal investigator of the BrainGate2 clinical trial.

Limitations

The researchers note that although the findings are promising, brain-to-voice neuroprostheses remain in an early phase. A key limitation is that the research was performed with a single participant with ALS. It will be crucial to replicate these results with more participants, including those who have speech loss from other causes, such as stroke.

Categories : Neurodegenerative DiseasesTags :

New Immune Solution Suggests Taking the STING out of Alzheimer’s

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A new way of thinking about Alzheimer’s disease has yielded a discovery that could be the key to stopping the cognitive decline seen in Alzheimer’s and other neurodegenerative diseases.

University of Virginia School of Medicine scientists have been investigating the possibility that Alzheimer’s is caused, at least in part, by the immune system’s wayward attempts to fix DNA damage in the brain. Their research reveals that an immune molecule called STING drives the formation of the harmful plaques and protein tangles thought responsible for Alzheimer’s. Blocking the molecule protected lab mice from mental decline, the researchers say.

An important player in the brain’s immune system, STING also may be a key contributor to Parkinson’s disease, amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease), dementia and other memory-robbing conditions. That means that developing treatments to control its activity could have far-reaching benefits for many patients facing now-devastating diagnoses.

“Our findings demonstrate that the DNA damage that naturally accumulates during aging triggers STING-mediated brain inflammation and neuronal damage in Alzheimer’s disease,” said researcher John Lukens, PhD, director of UVA’s Harrison Family Translational Research Center in Alzheimer’s and Neurodegenerative Diseases. “These results help to explain why aging is associated with increased Alzheimer’s risk and uncover a novel pathway to target in the treatment of neurodegenerative diseases.”

Alarming Trends in Alzheimer’s

Alzheimer’s is a growing problem, with researchers working frantically to find ways to better understand and treat the condition.

The causes of Alzheimer’s remain murky, but scientists are increasingly coming to appreciate the role of the immune system in the disease’s development. STING is part of that immune response; the molecule helps direct the clearance of viruses and stressed cells harboring DNA damage.

While STING is an important defender of the brain, it can also become hyperactive and cause harmful inflammation and tissue damage. That had Lukens and his team eager to determine what part it could be playing in Alzheimer’s. Blocking the molecule’s activity in lab mice, they found, helped prevent Alzheimer’s plaque formation, altered the activity of immune cells called microglia and redirected the workings of important genes, among other effects.

“We found that removing STING dampened microglial activation around amyloid plaques, protected nearby neurons from damage and improved memory function in Alzheimer’s model mice,” said researcher Jessica Thanos, part of UVA’s Department of Neuroscience and Center for Brain Immunology and Glia (BIG Center). “Together, these findings suggest that STING drives detrimental immune responses in the brain that exacerbate neuronal damage and contribute to cognitive decline in Alzheimer’s disease.”

Promising Treatment Target

While scientists have been investigating other molecules thought to be important in Alzheimer’s, STING makes for a particularly attractive target for developing new treatments, the UVA Health researchers say. That’s because blocking STING appears to slow both the buildup of amyloid plaques and the development of tau tangles, the two leading candidates for the cause of Alzheimer’s. Other molecules lack that robust involvement, and, further, could be targeted only at very specific – and very limited – stages in the disease’s progression.

“We are only beginning to understand the complex role of innate immune activation in the brain, and this is especially true in both normal and pathological aging,” Thanos said. “If we can pinpoint which cells and signals sustain that activation, we will be in a much better position to intervene effectively in disease.”

While Lukens’ pioneering research has opened new doors in the fight against Alzheimer’s, much more work will need to be done to translate the findings into treatments. For example, scientists will need to better understand STING’s roles in the body – such as in the immune system’s response to cancer – to ensure any new treatment doesn’t cause unwanted side effects.

But those are the types of big questions that Lukens and his collaborators at the Harrison Family Translational Research Center are eager to tackle as part of their efforts to fast-track new treatments and, eventually, they hope, cures.

“Our hope is that this work moves us close to finding safer and more effective ways to protect the aging brain, as there is an urgent need for treatments that can slow or prevent neuronal damage in Alzheimer’s,” Lukens said. “Shedding light on how STING contributes to that damage may help us target similar molecules and ultimately develop effective disease-modifying treatments.”

Source: University of Virginia Health System

Categories : Genetics Neurodegenerative DiseasesTags :

Common Gene Variant Doubles Dementia Risk for Men

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New research has found that men who carry a common genetic variant are twice as likely to develop dementia in their lifetime compared to women. The research, published in Neurology, used data from the ASPirin in Reducing Events in the Elderly (ASPREE) trial to investigate whether people who had variants in the haemochromatosis (HFE) gene, which is critical for regulating iron levels in the body, might be at increased risk of dementia.

Co-author Professor John Olynyk, from the Curtin Medical School, said one in three people carry one copy of the variant, known as H63D, while one in 36 carry two copies.

“Having just one copy of this gene variant does not impact someone’s health or increase their risk of dementia. However, having two copies of the variant more than doubled the risk of dementia in men, but not women,” Professor Olynyk said.

“While the genetic variant itself cannot be changed, the brain pathways which it affects – leading to the damage that causes dementia – could potentially be treated if we understood more about it.”

Professor Olynyk said further research was needed to investigate why this genetic variant increased the risk of dementia for males but not females.

“The HFE gene is routinely tested for in most Western countries including Australia when assessing people for haemochromatosis – a disorder that causes the body to absorb too much iron. Our findings suggest that perhaps this testing could be offered to men more broadly,” Professor Olynyk said.

“While the HFE gene is critical for controlling iron levels in the body, we found no direct link between iron levels in the blood and increased dementia risk in affected men.

“This points to other mechanisms at play, possibly involving the increased risk of brain injury from inflammation and cell damage in the body.”

The ASPREE trial was a double-blind, randomised, placebo-controlled trial of daily low-aspirin in 19 114 healthy older people in Australia and the USA. Primarily undertaken to evaluate the risks versus benefits of daily low-dose aspirin in this cohort, it created a treasure trove of healthy ageing data that has underpinned a wealth of research studies.

Source: Curtin University

Categories : Neurodegenerative Diseases NeurologyTags :

Autism Linked to Elevated Risk of Parkinson’s Disease

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People with an autism diagnosis are at a higher risk of developing Parkinson’s disease early in life, according to a large-scale study from Karolinska Institutet. The researchers believe that the two conditions can share underlying biological mechanisms.

The study, published in JAMA Neurology, is based on registry data from over two million people born in Sweden between 1974 and 1999 who were followed from the age of 20 up to the end of 2022.

The researchers interrogated a possible connection between the neuropsychiatric diagnosis Autism Spectrum Disorder (ASD), which affects an individual’s thought processes, behaviour and interpersonal communication, and early-onset Parkinson’s disease, a condition that affects locomotion and movement.

Possible dopamine involvment

The results show that people with an autism diagnosis were four times more likely to develop Parkinson’s disease than people without such a diagnosis, a correlation that remained when controlling for socioeconomic status, a genetic predisposition for mental illness or Parkinson’s disease and other such factors.

“This indicates that there can be shared biological drivers behind ASD and Parkinson’s disease,” says first author Weiyao Yin at the Department of Medical Epidemiology and Biostatistics. “One hypothesis is that the brain’s dopamine system is affected in both cases, since the neurotransmitter dopamine plays an important part in social behaviour and motion control.”

It is well-known that dopamine-producing neurons are degraded in Parkinson’s disease. Previous studies have also shown that dopamine is possibly implicated in autism, but more research needs to be done to confirm this.

“We hope that our results will eventually help to bring greater clarity to the underlying causes of both ASD and Parkinson’s disease,” says Dr Yin.

Medical checkups are vital

Depression and the use of antidepressants are common in people with autism, as are antipsychotic drugs, which are known for being able to cause Parkinson’s-like symptoms. When the researchers adjusted for these factors, the correlation between ASD and the later development of Parkinson’s disease was less salient, but the risk was still double.

The researchers point out that they only analysed early-onset Parkinson’s disease before the age of 50 and that the average age of participants by the end of the study was 34. The incidence of Parkinson’s disease was therefore very low. Future studies will need to examine if the elevated risk persists into older age. 

“The healthcare services need to keep people with ASD – a vulnerable group with high co-morbidity and a high use of psychotropics – under long-term observation,” says last author Sven Sandin, statistician and epidemiologist at the Department of Medical Epidemiology and Biostatistics. “At the same time, it’s important to remember that a Parkinson’s diagnosis before the age of 50 is very rare, including for people with autism.”

Source: Karolinska Institutet