The Journal of Clinical Investigation

How can we improve kidney repair while reducing kidney fibrosis? Xunrong Luo & team discover deletion of Allograft Inflammatory Factor-1 (Aif1) uniquely uncouples macrophage pro-reparative from pro-fibrotic functions, thereby promoting kidney repair while mitigating kidney fibrosis after ischemia-reperfusion injury: https://lnkd.in/eEAw7ENc The figure shows TUNEL staining of kidney sections in WT or Aif1-deletion mice

What is the disease mechanism in drug-resistant epilepsy? Jiadong Chen & team analyzed nearly 200 neurons from postsurgical brain tissue and discovered markers of neuronal senescence: https://lnkd.in/dcxwXpXT The figure shows an aberrant dendritic architecture of a pathological neuron, which was intracellularly loaded with biocytin and stained by streptavidin.

A blood test for asthma? Reynold A. Panettieri, Jr. & team show serum cAMP levels are increased in patients with asthma: https://lnkd.in/euMhZvka

Does autoimmunity underlie minimal change disease? Tobias B. Huber, Nicola M. Tomas & team report a direct pathogenic role of anti-nephrin autoantibodies in the development of podocytopathy with a minimal change disease phenotype: https://lnkd.in/em6nCi4B The electron microscopy image shows moderate podocyte foot process effacement (without electron-dense deposits) in the anti-nephrin rabbit.

Get a whiff of this! Yang-Xin Fu & team show the intranasal vaccine booster after intramuscular prime enhances mucosal immunity against SARS-CoV-2: https://lnkd.in/d4jD6PsC

Personalized or one-size-fits-all: The phage therapy field's favorite binary — or is it? We decided to look at how phage therapy is actually being implemented, & let the similarities & differences emerge. Excited to share our new review in The Journal of Clinical Investigation! A mega team effort spanning Stanford University, Yale University, Mayo Clinic, KU Leuven, & Queen Astrid Military Hospital, driven by my incredible colleague Kevin Minyoung Kim! Here's what we cover: ?? Pharma isn't touching phage therapy right now, but patients need it. In response, we're seeing phage therapy centers sprouting globally (QAMH, Center for Innovative Phage Applications and Therapeutics (IPATH), Baylor College of Medicine's TAILOR Labs, Phage Australia, & more). ?? Each 'phage therapy center' has a different approach (& does different things in-house), but considered together, a cohesive process emerges. From phage banking to susceptibility testing, manufacturing, quality control, & therapeutic monitoring, there are common needs & choices made at each step. ?? The spectrum of approaches is fascinating – people are getting creative, depending on what constraints & resources they have! We see fully patient-specific preparations, fixed broad-coverage cocktails, & hybrid models across many dimensions (eg. matching phages to a patient, but still combining them into a cocktail (or not), and/or using it again on the next patient; some groups outsource manufacturing, others give cocktails but personalize the monitoring). ?? Of course, scaling up often means making phage therapy into a drug. So we also took a look at the phage therapy process through a drug development lens, & laid out the gaps we see (cocktail design optimization / formulation challenges / pharmacokinetic modeling / clinical trial design). ?? Overall, despite impressive clinical outcomes when patients are treated with phages (clinical improvement of >70% across 1000+ published cases; and this is for patients where nothing else worked!), significant barriers remain for phage therapy implementation, no matter which way you do it. ?? Unfortunately, even if we fill ALL the technical gaps and make phages look like drugs, that doesn't fix the issue that almost NO ONE is funding antimicrobials. This is one of those things that will likely require dedicated public funding. It's like climate change — no one's problem today, everyone's problem tomorrow. ?? However, with the right support, we could lay the infrastructure so patients CAN get their multi-drug resistant infections treated. We hope this review helps lay out HOW phage therapy is currently getting the fantastic results it's been getting in the clinic, & inspires anyone who wants to set up their own pipeline / help push this boulder up the hill. Thanks so much to my mentor Paul Bollyky for encouraging us to tackle this topic, & handing me the reins as my first project here at Stanford! Here's the paper: https://lnkd.in/gufRRxD7

?? Partnership Opportunity Spotlight. Just published in The Journal of Clinical Investigation,?New York University researchers have identified novel therapeutic targets for treating chronic pain and developed inhibitory peptides that show efficacy in mouse models of pain as well as?on?human nociceptors (specialized sensory neurons that transmit pain signals to the brain). The peptides represent promising starting points for further optimization into therapeutic lead candidates for non-opioid treatment of multiple forms of Nerve Growth Factor (NGF)-mediated chronic pain, including arthritis and cancer pain. ?? Read more about this promising innovation here, DOI: https://lnkd.in/etpJWUUU ??We are looking for a strategic partner to help #commercialize these promising therapeutic candidates! To learn more about the innovation and how to partner with us,?visit??https://lnkd.in/ejXZXE9k or contact business development manager Douglas Brawley, PhD or licensing associate Keaton Crosse, PhD #pain #nonopioid #chronicpain #arthritispain #nervegrowthfactor #NGF #paintreatment #therapeutic New York University - College of Dentistry

A blood test for spinal injury? Chetan Bettegowda and team detected spinal cord-derived cfDNA and changes in plasma proteins from patients with acute spinal cord injury: https://lnkd.in/eyFdFDjR

Bridging the gap: Insights into sensory-motor deficits in NMDA receptor antibody encephalitis: https://lnkd.in/ehUCp8Am Puneet Opal and Geoffrey T. Swanson comment on Zhou et al. (https://lnkd.in/eD3KwBp5)

Imatinib on target in stroke recovery: https://lnkd.in/e5zt5Y4U Hae Ryong Kwon and Lorin E. Olson comment on Protzmann et al. (https://lnkd.in/dDMEdt5K)