A groundbreaking trial of an interactive game that trains people to alter their brain waves has shown promise as a treatment for nerve pain – offering hope for a new generation of drug-free treatments.

The PainWaive technology, developed by UNSW Sydney researchers, teaches users how to regulate abnormal brain activity linked to chronic nerve pain, providing a potential in-home, non-invasive alternative to opioids.

A recent trial led by Professor Sylvia Gustin and Dr Negin Hesam-Shariati from UNSW Sydney’s NeuroRecovery Research Hub has delivered promising results, published in the Journal of Pain. The study compared hundreds of measures across participants’ pain and related issues like pain interference before, during, and after four weeks of interactive game play.

Their brain activity was tracked via EEG (electroencephalogram) headsets, with the app responding in real time to shifts in brainwave patterns. Three out of the four participants showed significant reductions in pain, particularly nearing the end of the treatment. Overall, the pain relief achieved by the three was comparable to or greater than that offered by opioids.

“Restrictions in the study’s size, design, and duration limit our ability to generalise the findings or rule out placebo effects,” Dr Hesam-Shariati says. “But the results we’ve seen are exciting and give us confidence to move to the next stage and our larger trial.”

The PainWaive project builds on UNSW Professor Sylvia Gustin’s seminal research into changes in the brain’s thalamus – a central relay hub in the brain – associated with nerve (neuropathic) pain. “The brainwaves of people with neuropathic pain show a distinct pattern: more slow theta waves, fewer alpha waves, and more fast, high beta waves,” Prof. Gustin says.

“We believe these changes interfere with how the thalamus talks to other parts of the brain, especially the sensory motor cortex, which registers pain.” I wondered, can we develop a treatment that directly targets and normalises these abnormal waves?” The challenge was taken up by an interdisciplinary team at UNSW Science and Neuroscience Research Australia (NeuRA), led by Prof. Gustin and Dr Hesam-Shariati, and resulted in PainWaive.

The four participants in its first trial received a kit with a headset and a tablet preloaded with the game app, which includes directions for its use. They were also given tips for different mental strategies, like relaxing or focusing on happy memories, to help bring their brain activity into a more “normal” state. The user data was uploaded to the research team for remote monitoring.

“After just a couple of Zoom sessions, participants were able to run the treatment entirely on their own,” says Dr Hesam-Shariati. “Participants felt empowered to manage their pain in their own environment. That’s a huge part of what makes this special.”

Initially, Dr Hesam-Shariati says, the team planned to use existing commercial EEG systems but were either too expensive or didn’t meet the quality needed to deliver the project. Instead, they developed their own. “Everything except the open-source EEG board was built in-house,” says Dr Hesam-Shariati.

“And soon, even that will be replaced by a custom-designed board.” Thanks to 3D printing, Prof. Gustin says, the team has cut the cost of each headset to around $300 – a fraction of the $1,000 to $20,000 price tags of existing systems.

The headset uses a saline-based wet electrode system to improve signal quality and targets the sensorimotor cortex. “We’ve worked closely with patients to ensure the headset is lightweight, comfortable, and user-friendly,” says Prof. Gustin.

The researchers are now calling for participants to register their interest in two upcoming trials of the neuromodulation technology: the Spinal Pain Trial, investigating its potential to reduce chronic spinal pain, and the StoPain Trial, exploring its use in treating chronic neuropathic pain in people with a spinal cord injury.

Breaking New Ground: Immune System Discovery Offers Potential Solution to Alzheimer’s

A groundbreaking study has shed new light on the relationship between the immune system and Alzheimer’s disease. Researchers at the University of Virginia School of Medicine have discovered that an immune molecule called STING plays a crucial role in driving the formation of amyloid plaques and tau tangles, hallmarks of Alzheimer’s.

The study found that blocking STING activity in lab mice protected them from mental decline, suggesting a promising new target for developing treatments. This breakthrough has far-reaching implications for understanding and treating not only Alzheimer’s but also other neurodegenerative diseases like Parkinson’s disease, amyotrophic lateral sclerosis (ALS), and dementia.

“The 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. “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.”

The study, published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, involved a team of researchers from UVA’s Department of Neuroscience and Center for Brain Immunology and Glia (BIG Center). They found that removing STING dampened microglial activation around amyloid plaques, protected nearby neurons from damage, and improved memory function in Alzheimer’s model mice.

The discovery of STING as a key player in the development of neurodegenerative diseases opens new doors for research into potential treatments. While much more work is needed to translate these findings into effective therapies, this breakthrough has sparked hope among researchers and patients alike.

“Our hope is that this work moves us close to finding safer and more effective ways to protect the aging brain,” said Lukens. “Shedding light on how STING contributes to that damage may help us target similar molecules and ultimately develop effective disease-modifying treatments.”

The APOE gene is a major genetic risk factor for Alzheimer’s disease, with three different versions: APOE2, APOE3, and APOE4. While APOE4 increases the risk of developing Alzheimer’s, APOE2 is associated with a lower risk. However, how these isoforms lead to strikingly different risk profiles is poorly understood.

A recent study published in Nature Communications offers clues into how APOE isoforms differentially affect human microglia function in Alzheimer’s disease. The study, led by Dr. Sarah Marzi and Dr. Kitty Murphy at the UK Dementia Research Institute at King’s College London and the Department of Basic and Clinical Neuroscience, underscores the need for new targeted interventions based on APOE genotypes.

The researchers developed a human “xenotransplantation model,” where human microglia were grown from stem cells, manipulated to express different APOE versions, then transplanted into the brains of mice that had developed a buildup of amyloid plaques. The microglia were then isolated and analyzed for their gene expression (using transcriptomics) and chromatin accessibility.

The study uncovered widespread changes to the transcriptomic and chromatin landscape of microglia, dependent on the APOE isoform expressed. The largest differences were observed when comparing the APOE2 and APOE4 microglia.

In APOE4 microglia, researchers saw an increase in the production of cytokines, signaling molecules involved in immune regulation. They also observed diminished capacity for the microglia to migrate and shift into protective states. Furthermore, the microglia became less effective in phagocytosis, a process by which they digest and clear up particles such as debris and pathogens.

Conversely, APOE2 microglia showed increased expression of various genes that increase microglia proliferation and migration, and a decreased inflammatory immune response. Additionally, APOE2 microglia showed increased DNA-binding of the vitamin D receptor. Low levels of vitamin D have been associated with a higher incidence of Alzheimer’s.

The study highlights that microglia responses to amyloid pathology differ significantly across APOE versions. This finding underscores that considering the interplay between genetic risk factors and microglial states is critical in disease progression. The study also highlights the potential role of the vitamin D receptor, providing new avenues for therapeutic exploration.

Dr. Sarah Marzi, Senior Lecturer in Neuroscience at King’s College London and lead author of the study, said: “Our findings emphasize that there is a complex interplay between genetic, epigenetic, and environmental factors that influence microglial responses in Alzheimer’s disease. We found remarkable differences when comparing microglia expressing different isoforms of the same gene. Our research suggests that microglia expressing the risk-increasing APOE4 variant are not as effective at mounting protective microglial functions, including cell migration, phagocytosis and anti-inflammatory signaling. This underscores the need for targeted interventions based on APOE genotype.”