A mitochondrial protein indirectly supports antidepressant BDNF signaling in the brain.
Category: biotech/medical – Page 58
New Alzheimer’s Treatment Strategy Reverses Cognitive Decline in Mice
Researchers have developed a novel compound that could transform the way we treat Alzheimer’s disease, offering not just a new weapon but potentially a new strategy for battling the most common form of dementia worldwide.
While current drugs for Alzheimer’s mostly focus on removing amyloid-beta plaques associated with the disease, the new compound takes a fundamentally different approach, instead targeting a specific enzyme to therapeutically reprogram the epigenome of neurons – a series of molecular marks that can be added to or removed from DNA, to change the way genes work.
Monoclonal antibody drugs such as lecanemab and donanemab, which target amyloid-beta proteins, help somewhat to slow the progression of the disease when treatment is started early, but there is still no proven way to reverse cognitive decline from Alzheimer’s in humans.
Ganglion Cell Layer Compared With Inner Plexiform Layer Atrophy After Optic Neuritis Associated With NMOSD, MOGAD, and MS
In a phase 3 randomized clinical trial of adults with ParkinsonDisease experiencing motor fluctuations despite stable levodopa therapy, adjunctive tavapadon—a once-daily, selective D1/D5 dopamine agonist—significantly increased daily on-time without troublesome dyskinesia and reduced off-time compared with placebo over 27 weeks.
Most adverse events, including nausea, dyskinesia, and dizziness, were mild to moderate. Tavapadon showed a favorable safety profile and provided clinically meaningful motor improvements as adjunctive therapy.
Question Can adjunctive tavapadon—an oral, once-daily, selective dopamine (D) D1/D5 agonist—improve motor control for people with Parkinson disease (PD) experiencing motor fluctuations while minimizing risk of adverse events?
Findings In this phase 3, double-blind, placebo-controlled, 27-week randomized clinical trial of 507 participants with PD, tavapadon significantly increased daily on-time without troublesome dyskinesia (good-on-time) vs placebo. Most adverse events were mild to moderate in severity with nausea, dyskinesia, and dizziness most common with tavapadon.
Meaning Results show that tavapadon adjunctive to levodopa provided clinically meaningful motor improvements and an acceptable safety profile in adults with PD experiencing motor fluctuations while receiving oral levodopa.
New genetic risk score better predicts diabetes, obesity and downstream complications
Type 2 diabetes (T2D) and obesity are metabolic conditions with many causes, including overlapping and distinct genetic features. A polygenic risk score (PRS) can capture multiple genetic risk factors to provide an estimate for whether a person may develop a complex medical condition and how they might fare long-term.
Building stronger genetic risk scores By integrating genetic findings from several of the world’s largest biobanks, investigators from Mass General Brigham built metabolic PRSs for predicting obesity and T2D, which outperformed existing disease-prediction models and predicted downstream morbidity and clinical interventions. Findings are published in Cell Metabolism.
“Our intention was to not only capture the risk of being diagnosed with obesity or diabetes, but also to better predict health consequences across the life course by integrating many aspects of metabolic function,” said co-first author Min Seo Kim, MD, MSc.
Aging Can be Slowed Down
Scientists are studying a protein called HMGB1 that’s released by damaged or stressed cells and can trigger inflammation in nearby healthy cells, accelerating the aging process. If this research holds up, it could completely change how we think about aging and disease.
Designed to remember
In a new Science study, researchers report that specific regions dense in cytosine and guanosine dinucleotides are epigenetically modified during inflammation to enable gene expression and that these changes persist during the animal’s lifetime.
The finding has implications for understanding how the genome determines the longevity of memory, which affects tissue fitness.
Learn more in a new Science Perspective.
Specific DNA sequence features encode the persistence of epigenetic memory of inflammation.
Guillaume Blot and Przemyslaw Sapieha Authors Info & Affiliations
Science
How stimulating the vagus nerve could protect the brain from Alzheimer’s disease
Developing tau tangles doesn’t mean a person has Alzheimer’s disease – in fact, it happens to nearly everyone to varying degrees. But because these changes start in the locus coeruleus, some brain researchers – myself included – see this area as a canary in the coal mine for developing Alzheimer’s disease.
We are exploring whether stopping or slowing down tau tangles in this brain region, or otherwise maintaining its health, may be a way to interrupt how the disease ultimately unfolds and to prevent other aspects of cognitive aging.
Emerging research from my lab and others is investigating the idea that a therapy called vagus nerve stimulation, which is already widely used for other health conditions, could be one way of keeping the locus coeruleus functioning properly.
Longevity Isn’t Equal: Why Life-Extending Treatments May Be a “Biological Lottery”
Extending life is only part of the goal in aging research. Scientists also want more people to reach old age in good health, with fewer differences in when individuals die. This ideal outcome is often described as “squaring the survival curve,” where most deaths are pushed into a narrow window late in life rather than spread out across many years.
To test how close current science comes to that goal, University of Sydney researchers revisited a large meta-analysis of studies in vertebrates. They focused on three widely studied interventions: dietary restriction, rapamycin, and metformin. While all are linked to longevity, they work in different ways.
Dietary restriction involves reducing calorie intake without causing malnutrition. It has been known for more than a century to extend lifespan in animals and is thought to act in part by dialing down a key cellular growth pathway called mTORC1, which helps regulate metabolism and aging. Because strict diets are difficult to maintain, scientists have searched for drugs that mimic these effects. Rapamycin directly blocks mTORC1 activity, while metformin, a common diabetes medication, influences the same pathway indirectly by altering how cells sense energy levels.
Mesothelioma: a systemic therapy clinical trials snapshot
Systemic therapy targets in mesothelioma.
Recent changes to clinical practice have made modest improvements in 1– 2-year survival, but longer-term survival remains unchanged, and durable benefit is very rare.
Combining immunotherapy with chemotherapy, particularly with novel bispecific agents, may result in more therapeutic modalities being administered together in the first-line setting. The current evidence for second-line treatments is sparse.
New targeted-therapy strategies are promising. Early-phase clinical trials are showing signals of efficacy in mesotheliomas harboring MTAP loss or inactivation of the Hippo pathway.
Further studies will be needed to robustly confirm clinical benefit. sciencenewshighlights ScienceMission https://sciencemission.com/Mesothelioma
Mesothelioma is a rare cancer that has seen few incremental improvements in survival over the past two decades. However, a significantly improved understanding of the underlying biology has led to new therapeutic advances with the potential to improve clinical outcomes. In this review, we take a snapshot of the current systemic therapy research landscape, with our goal to forecast the trajectory of drug development for mesothelioma over the next half-decade. In our current census, we identify 106 active trials including systemic therapies: 20 (19%) are molecularly targeted, 26 (25%) include immunomodulation, and 12 (11%) combining immunotherapy with antiangiogenic therapies. Collectively, the landscape of therapeutic innovation for mesothelioma is expanding, bringing hope that improvements in life expectancy may follow.