STAT+: Oruka’s long-acting psoriasis therapy posts strong results in mid-stage study

A long-acting injectable treatment for plaque psoriasis helped 63% of patients achieve complete skin clearance in a mid-stage clinical trial, its maker, Oruka Therapeutics, reported Monday. 

Separately, Oruka said an updated analysis of blood exposure levels supported the potential for the drug, ORKA-001, to be injected just once per year. 

Oruka still needs to conduct late-stage clinical trials, but Monday’s results bolster ORKA-001’s potential to become a new treatment for the autoimmune skin disease with remission rates equal to or greater than current commercial blockbusters Skyrizi and Bimzelx, while requiring fewer injections.

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STAT+: Zap in a cap: How one neurotech startup is using a hat to treat depression

Wake up. Brush your teeth. Wash your face. 

And put on your lifesaving baseball hat.

That’s right. If you have treatment-resistant depression, this could be the regular morning routine in your future. The hat would activate a blueberry-sized device implanted in your skull that sends a pulse of electricity into your brain.

This is Jacob Robinson’s vision — and it got closer to reality on Friday after the Food and Drug Administration approved a request from Robinson’s startup, Motif Neurotech, to start an initial feasibility trial to test the efficacy of their device in treating depression that hasn’t responded to other treatments. Scientists have been zapping brains to alleviate depression for decades through a method called transcranial magnetic stimulation, or TMS. Motif wants to do the same thing, but with a twist.

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Abdominal Contractions May Drive Brain Fluid Flow, Aiding in Neural Waste Clearance

Data from a new study in Nature Neuroscience shows that the brain may be more mechanically connected to the body than previously appreciated. Using mice and computational simulations of fluid motion, the team identified a possible biological mechanism that helps explain why exercise benefits brain health. Specifically, they found that abdominal contractions compress blood vessels that are connected to the spinal cord and brain, which helps the organ move gently within the skull. This movement facilitates the flow of cerebrospinal fluid over the brain, potentially washing away neural waste and preventing the development of neurodegenerative disorders. 

The work, which is described in a paper titled “Brain motion is driven by mechanical coupling with the abdomen,” builds on past studies exploring how sleep and neuron loss influence how and when cerebrospinal fluid flushes the brain, according to Patrick Drew, PhD, a professor of engineering science and mechanics, neurosurgery, biology, and biomedical engineering at Penn State University. Drew is the corresponding author on the study. 

“Our research explains how just moving around might serve as an important physiological mechanism promoting brain health,” said Drew. The contraction of abdominal muscles to push blood from the abdomen into the spinal cord acts “just like in a hydraulic system” that puts pressure on the vertebral venous plexus, a network of veins that connect the abdominal cavity to the spinal cavity which causes the brain to move. Computational simulations show “that this gentle brain movement will drive fluid flow in and around the brain” removing harmful waste. 

To view this mechanism in moving mice, the scientists used two-photon microscopy, which allows for high-definition imaging of living tissue, and microcomputed tomography, which supports high-resolution three-dimensional examination of whole organs. They observed the brains shifting in the moments before the mouse moved and right after their abdominal muscles tightened, anticipating further movement. 

To ensure that the abdominal contractions were the reason for the observed shift rather than other movements, the scientists applied gentle and controlled pressure to the abdomens of anesthetized mice. They observed that the mice’s brains moved in response. “Importantly, the brain began moving back to its baseline position immediately upon relief of the abdominal pressure,” Drew said, suggesting “that abdominal pressure can rapidly and significantly alter the position of the brain within the skull.” 

The next step was digging deeper into the fluid’s movement in the brain as well as assessing if the brain’s movement could induce fluid flow. For this task, members of the team developed various techniques to capture this information including conducting imaging experiments of living mice and generating computational simulations of fluid motion. 

“Modeling fluid flow in and around the brain offers unique challenges because there are simultaneous, independent movements, as well as time-dependent, coupled movements,” explained Francesco Costanzo, PhD, a professor of engineering science and mechanics, biomedical engineering, mechanical engineering, and mathematics, who led the computational modeling aspects of the project. “Accounting for all of them requires accounting for the special physics that happens every time a fluid particle crosses one of the many membranes in the brain. So, we simplified it” using the analogy of a sponge for the brain. By simplifying it in this way, Costanzo explained, the team could model how fluid flows through a structure with varied spaces.  

Sticking with the analogy, “we also thought of it as a dirty sponge—how do you clean a dirty sponge?” Costanzo continued. “You run it under a tap and squeeze it out. In our simulations, we were able to get a sense of how the brain moving from an abdominal contraction can help induce fluid flow over the brain to help clear waste products.”  

Further studies are necessary to understand how this mechanism works in human bodies particularly how it cycle cerebrospinal fluid around the brain, and helps to protect against neurodegenerative disease. “This kind of motion is so small. It’s what’s generated when you walk or just contract your abdominal muscles, which you do when you engage in any physical behavior. It could make such a difference for your brain health,” Drew said.  Overall, “our research shows that a little bit of motion is good, and it could be another reason why exercise is good for our brain health.”  

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NIH-funded research lags in reporting sex differences, new study finds

Fewer than half of papers published by NIH-funded researchers analyze or report their data by sex, which could make it harder to know what the results mean for men and women, a new study found.

Over a decade ago, the National Institutes of Health set out to promote sex-inclusivity in study design by introducing the expectation that research it funded consider sex as a biological variable (SABV). The guidelines are broad, asking researchers to consider SABV in their design, analysis, and reporting, without mandating that sex differences be examined in the results. 

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Genetic risk for neurodevelopmental disorders as a potential factor affecting antipsychotic responsiveness in schizophrenia: a postmortem brain study

IntroductionSchizophrenia (SCZ) is a highly heritable neuropsychiatric disorder. Its genomic architecture reportedly overlaps with that of neurodevelopmental disorders, such as attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). However, the effect of genomic risk for ADHD and ASD on SCZ symptoms remains unclear.MethodWe obtained genome-wide association study (GWAS) data from the postmortem brains of 24 patients with SCZ and 48 controls and calculated the polygenic risk scores (PRSs) for ADHD (ADHD-PRS) and ASD (ASD-PRS) using publicly available GWAS data. For 19 patients with SCZ whose antemortem clinical information was available, we conducted correlation analyses between PRSs, severity of SCZ symptoms, and the antipsychotic responsiveness score (ARS). Additionally, we divided the patients into two subgroups based on ADHD-PRS (high and low ADHD-PRS groups) and performed exploratory gene expression analyses and subsequent pathway analysis in the prefrontal cortex.ResultsThe ARS of positive symptoms (ARS-PS) demonstrated a suggestive negative correlation with ADHD-PRS and a positive correlation with ASD-PRS although these associations did not survive multiple testing correction. No correlation was observed between the ARS of general psychopathology or the ARS of negative symptoms and either ADHD-PRS or ASD-PRS. Gene expression analysis identified 1,773 DEGs, including neuropsychiatric disorder-related genes including CHRNB2. These DEGs were enriched in pathways associated with the neuronal system and mitochondrial function.DiscussionOur findings suggest that the genomic risk for neurodevelopmental disorders may affect the antipsychotic responsiveness of patients with schizophrenia and implicate translational alterations in potential marker molecules in this phenotype. Due to the limited sample size in the current study, further investigation on the large cohort is required to verify our exploratory findings.