pregnenolone / Duke University Health System - LARVOL DELTA

PREG-AUD-RO1: Pregnenolone Treatment for Alcohol Use Disorder and Major Depressive Disorder (clinicaltrials.gov) - P2 | N=100 | Not yet recruiting | Sponsor: Sherwood Brown, MD, PhD

New P2 trial • Addiction (Opioid and Alcohol) • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Integrative plasma metabolomic profiling identifies distinct vascular and inflammatory signatures in hospital emergency department patients. (PubMed, Clin Chim Acta) - "Novel and distinct metabolomic signatures significantly associated with clinical outcomes were identified in patients with vascular and inflammatory conditions. The proposed biomarkers in this study may be viable tools for future development of strategies that may aid clinicians with timely treatment, monitoring and risk stratification of ED patients using a precision medicine-based approach."

Journal • Critical care

Suboptimal suppression of serum androgen levels among men treated with apalutamide and abiraterone acetate plus prednisone compared with abiraterone acetate plus prednisone alone. (ASCO 2025) - "Funded by Janssen Scientific Affairs, LLC Background: Phase III studies of dual therapy with an androgen receptor (AR) antagonist, apalutamide (Apa) or enzalutamide (Enza) with abiraterone acetate (AA) plus (+) prednisone (P) in metastatic castration resistant prostate cancer (mCRPC) have not shown a survival benefit vs single agent therapy...Despite the decrease in AA levels, steroids upstream of CYP17A in PANTHER were markedly elevated vs treatment with AA + P alone: pregnenolone (4.1 vs 0.79ng/ml, p=<0.0001), consistent with a suboptimal prednisone-mediated suppression of ACTH Serum AA levels at week 4 are substantially lower, and androgen levels substantially higher, among men with mCRPC treated with Apa and AA + P vs AA + P. Our data suggest that Apa decreased P levels to the point that circulating ACTH remained sufficient to mediate ongoing basal adrenal androgen synthesis... Serum AA levels at week 4 are substantially lower, and androgen levels substantially..."

Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CYP17A1 • CYP3A4

Molecular basis of neurosteroid and anticonvulsant regulation of TRPM3. (PubMed, Nat Struct Mol Biol) - "Transient receptor potential channel subfamily M member 3 (TRPM3) is a Ca2+-permeable cation channel activated by the neurosteroid pregnenolone sulfate (PregS) or heat, serving as a nociceptor in the peripheral sensory system. Here we present cryogenic electron microscopy structures of the mouse TRPM3 in complex with cholesteryl hemisuccinate, primidone and PregS with the synthetic agonist CIM 0216. Our studies identify the binding sites for the neurosteroid, synthetic agonist and inhibitor and offer insights into their effects and disease mutations on TRPM3 gating, aiding future drug development."

Journal • CNS Disorders • Developmental Disorders • Psychiatry • TRPM3

Neuroactive Steroids, Toll-like Receptors, and Neuroimmune Regulation: Insights into Their Impact on Neuropsychiatric Disorders. (PubMed, Life (Basel)) - "Pregnane neuroactive steroids, notably allopregnanolone and pregnenolone, exhibit efficacy in mitigating inflammatory signals triggered by toll-like receptor (TLR) activation, thus attenuating the production of inflammatory factors. Clinical studies highlight their therapeutic potential, particularly in conditions like postpartum depression (PPD), where the FDA-approved compound brexanolone, an intravenous formulation of allopregnanolone, effectively suppresses TLR-mediated inflammatory pathways, predicting symptom improvement...This review emphasizes the significant therapeutic potential of neuroactive steroids in modulating TLR signaling pathways, particularly in addressing inflammatory processes associated with neuropsychiatric disorders. It advances our understanding of the complex interplay between neuroactive steroids and immune responses, paving the way for personalized treatment strategies tailored to individual needs and providing insights for future research..."

IO biomarker • Journal • Review • CNS Disorders • Depression • Inflammation • Mental Retardation • Postpartum Depression • Psychiatry

White Matter Microstructure is Associated with Serum Neuroactive Steroids and Psychological Functioning. (PubMed, J Neurotrauma) - "This study provides novel insight into a potential common pathophysiological mechanism of neurosteroid dysregulation underlying the high risk for mental health issues in military service members. Further, comorbidity of PTSD and mTBI may bring the compensatory effects of the brain's stress response to their limit. Future research is needed to investigate whether neurosteroid regulation may be a promising tool for restoring brain health and improving psychological functioning."

Journal • CNS Disorders • Post-traumatic Stress Disorder • Vascular Neurology

"Adding to the literature on cabozantinib-nivolumab, synergy in combo controlling #kidneycancer refractory to either alone. Great persistence from @ChesterKao1 @IMResidencyDuke pushing this out! #dukefamily @DukeGUCancer @dukemedicine" (,@TiansterZhang)

Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

"A renaissance of cabozantinib in prostate cancer? @MRHarrisonMD leading the SPARC IST @DukeGUCancer. Excited for this and CONTACT-02 to show how cabozantinib might be useful for prostate cancer. @montypal @neerajaiims" (,@TiansterZhang)

Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

".@Jeanna_BlitzMD @JenDominguezMD @EbonyJHilton_MD @dremilym @womenMDinanesth @WomenInCTAnes @mswami001 @SashaShillcutt @RUBraveEnough @EMARIANOMD @KarenSibertMD @APSForg @ASALifeline @DukeAnesRes @Duke_Anesthesia" (,@ebmalinzakMD)

Clinical

"@Roche @SustainBrandsJP @PhilharmonieLux @PwC_Luxembourg @fastinformfi duchess 👑⚜️Gabriella Archduke C hristophe #Lorraine #habsbourg Austria🇦🇹⚜️ duke Prince👑⚜️luxmbourg🇱🇺⚜️ DC🗽 #bridal👰 duchess 👑kathleenne ceremony" (,@CoRouis)

"Thanks @DrCJohns ! Some others: @CharlenePringl1 @DrSYIrving @LifeWithoutDiet @dukeacpnp @Skuttle0066M" (,@brownam130)

"$DUK Duke Energy Implements Trellis Platform to Improve Natural Gas Forecasting and Purchasing for Large Industrial Customers https://t.co/wVFz7HxFcB" (,@stock_titan)

"Not too late to sign up! #jacchf @JACCJournals @DukeHFDoc @coconnormd" (,@mfiuzat)

"Nice work being led by Anthony Sung, MD @DukeHMCT & @Paul_Wischmeyer" (,@DukeHMCT)

"Congrats! Welcome to @DukeU !" (,@mswami001)

"@MKIttleson @DukeHFdoc @AmDiabetesAssn @JavedButler1 @Ethanjweiss #Diabetes #Glucose #Endocrinology" (,@CardioVisualApp)

Diabetes • Metabolic Disorders

"@DukeCancerNETWK @DukeCancer @NCIMedia @NCIResearchCtr @theNCI @ASCO @ASCOPost @CCITdk @CancerDotNet @DukeHealth @bmsnews @DrChoueiri @Endocrine_News @EndoMedia" (,@CheckpointNowMD)

Oncology

"Congrats new #ACCFITs !! @DukeCardFellows @emory_heart @UTSWCardfellow @UMassCardio @uclaCVfellows @BrownCardiology @BeaumontCards @BrighamFellows @CCFcards @OHSUCardFellow @TempleCards @UCCardsFellows @MSMCardsFellows @UCSF_CVfellows @cardionerds @global_wic" (,@gina_lundberg)

Clinical • Cardiovascular

"Carry V’s story of M’s experience from our first @DukeForge convo in my ❤️" (,@azaleakim)

"How reduced CO and/or reduced EF (and current definitions of #HF) explain paroxysmal nocturnal dyspnea and nocturia in HF? @NMHheartdoc @gcfmd @HFpEF @dmljmd, @robmentz @PeterEckmanMD @mvaduganathan @JacobNiall @DukeHFDoc @ShelleyZieroth @JonathanDavisHF @rcstarling @LiviuKlein" (,@tigranmd)

"Indeed, no better companions in the trenches than the @DukeCardFellows A true fellowship in all respects." (,@ZainabASamad)

"@mayocvonc @arjunkg @husam247 @NakhterMD @CarolCardioOnc @drbrowncares @BrentonBauerMD @CardioOnc_MR_CT @sdent_duke @Dr_RoohiKhan @DrRohitMoudgil @vgzmd @Vijayrao7474 @KerrySkurka @DanielSierraMD8 @DrTochiOkwuosa @franckthuny @daniele_andres" (,@datsunian)

"Thanks @leejanhau for the tag! 1) #pedsICU RT, ECMO specialist & researcher @DukeHealth 2) Mechanical ventilation, asthma, burnout, airway management - collaborative networks 3) Huge Star Wars fan - #TheMandalorian @pendelluft @BrianKWalsh @dukeacpnp @afeldtx @edithmd251" (,@AGMRRT)

Asthma • Immunology • Respiratory Diseases

"Congratulations!!! Lucky Duke! Well deserved!!!" (,@Filippatos)

"Thanks @DukeHFDoc !" (,@KSharmaMD)