Andrés D. Klein’s Post

At Kapoose Creek Bio, we're continuing to share our science at major conferences. Last week, Dr. Timsy Bhando presented a poster at the 7th Annual Neuropsychiatric Drug Development Summit in Boston, highlighting research on our lead molecule KCB-100. KCB-100 shows neurotrophic, neuritogenic, and synaptogenic activities, working through the BDNF (brain-derived neurotrophic factor) signalling pathway. BDNF is critical for neuron survival, growth, and synaptic plasticity, and this molecule’s ability to activate these pathways presents exciting opportunities for treating neurodegenerative diseases and improving brain health. To top it off, KCB-100 also demonstrates blood-brain barrier (BBB) permeability in in-vivo models, bringing us one step closer to delivering effective CNS therapies. Kapoose Creek Bio is thrilled to leverage our AI technology to optimize the KCB-100 compound for human dosing, inching ever closer towards the clinical development of a Drug Candidate in the coming months. Exciting times! #Neuroscience #BDNF #DrugDiscovery #CNSResearch #BloodBrainBarrier #Neurotrophic #Neurodegeneration #PharmaInnovation

What do Major Depressive Disorder and the cerebral vasculature have to do with one another? Here are 5 things I recently learned: 1) Clinical and preclinical data suggest that brain blood vessels are more permeable in MDD patients and animal models of MDD. 2) Brain blood vessel permeability is especially pronounced in brain areas typically associated with pleasure and reward. 3) Molecules released from cells that make up brain blood vessels can regulate and prevent death of neurons, especially during stressful conditions. 4) Researchers think trophic factors (molecules responsible for cell reproduction and growth, e.g. BDNF) may explain the therapeutic activity of antidepressants. 5) Cells that make up brain blood vessels may be a source of trophic factors able to prevent neuron death during stressful conditions. What are your thoughts? Had you previously heard of the involvement of the cerebral vasculature in MDD? Could BBB targeted drugs prove beneficial toward developing new antidepressants? #Research #ScienceCommunication #Neuroscience #BloodBrainBarrier #MentalHealth #BBBResearch Sources: 1) Menard C, Pfau ML, Hodes GE, et al. Social stress induces neurovascular pathology promoting depression. Nat Neurosci. 2017;20(12):1752-1760. doi:10.1038/s41593-017-0010-3 2) Guo S, Som AT, Waeber C, Lo EH. Vascular neuroprotection via TrkB- and Akt-dependent cell survival signaling. In: Journal of Neurochemistry. Vol 123. J Neurochem; 2012:58-64. doi:10.1111/j.1471-4159.2012.07944.x 3) Casarotto PC, Girych M, Fred SM, et al. Antidepressant drugs act by directly binding to TRKB neurotrophin receptors. Cell. 2021;184(5):1299-1313.e19. doi:10.1016/j.cell.2021.01.034

Roche Strikes Again! "After a year of treatment, our BTK inhibitor fenebrutinib was able to suppress nearly all disease activity and disability progression in people with multiple sclerosis," said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer. This could be a major breakthrough in MS treatment, as 96% of patients in the OLE period were relapse-free, with a remarkable 0.04 annualized relapse rate (ARR). MRI results also showcased 99% reduction in active inflammation and a threefold decrease in chronic disease burden. With promising ongoing Phase III trials, fenebrutinib may soon reshape the future of MS care! Stay tuned for more in 2025. #MultipleSclerosis #Neuroscience #RocheInnovation #Fenebrutinib #ClinicalResearch #Pharma

Small-molecule-induced epigenetic reprograming of lipid metabolism inducing CNS myelin regeneration Published in Cell, this article describes that oligodendrocytes in MS lesions are present but epigenetically silenced, preventing myelin production. Researchers developed a molecule (ESI1) that reverses this silencing, promoting remyelination in animal models and improving cognitive function in aged mice. ESI1 reprograms lipid metabolism in oligodendrocytes to enhance myelin production and potentially offers a new approach to treating demyelinating diseases. https://lnkd.in/edKwZa_C #genetics #genomics #precisionmedicine #genomicmedicine #epigenetics #omics #smallmolecule #brain #neurology #neurodegeneration #neuroscience #ms #multiplesclerosis #biotechnology #therapeutics #aging #longevity #dementia #innovation #research #science #lipids #metabolism #sciencecommunication

🎊 New Review Alert 🌞 🌈 Title: Breaking the amyotrophic lateral sclerosis early diagnostic barrier: the promise of general markers 🧐 Authors: Yizhou Lu†, Lu He†, Huanyu Meng, Sheng Chen*, Qinming Zhou 📍 Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease that is associated with selective and progressive loss of motor neurons. As a consequence, the symptoms of ALS are muscle cramps and weakness, and it eventually leads to death. 🔗 Read Online: https://lnkd.in/gGuzUvr2 📄 PDF: https://lnkd.in/gmwekWp5 #AmyotrophicLateralSclerosis #Marker #Genes #Neurofilament #MagneticResonanceImaging #PositronEmissionTomography #Neurophysiology #Neuroultrasound

"Damage to the optic nerve can lead to irreversible blindness. A newly investigated regeneration factor could change that, UConn researchers report in the May 2024 issue of Experimental Neurology. Blindness and vision impairment due to optic nerve damage affect more than 3 million people in the U.S. alone, according to the Centers for Disease Control (CDC). The most common reason for that damage is glaucoma, a family of eye diseases that affect the flow of liquid in the eye, eventually damaging the long bundle of cells that connect the retina to the brain. That bundle of cells is the optic nerve. They don't grow back after being damaged, leading to permanent vision loss. Now, a team of researchers in the lab of UConn School of Medicine neuroscientist Ephraim Trakhtenberg have shown that a protein previously thought unimportant can stimulate regrowth of nerve cells. The protein is called nuclear factor erythroid 3 (Nfe3), and it is unique to nerves originating in the retina. Normally it is not produced by adult neurons." #nerveregeneration #blindness #vision

🎊 New Review Alert 🌞 🌈 Title: Breaking the amyotrophic lateral sclerosis early diagnostic barrier: the promise of general markers 🧐 Authors: Yizhou Lu†, Lu He†, Huanyu Meng, Sheng Chen*, Qinming Zhou 📍 Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease that is associated with selective and progressive loss of motor neurons. As a consequence, the symptoms of ALS are muscle cramps and weakness, and it eventually leads to death. 🔗 Read Online: https://lnkd.in/gGuzUvr2 📄 PDF: https://lnkd.in/gmwekWp5 #AmyotrophicLateralSclerosis #Marker #Genes #Neurofilament #MagneticResonanceImaging #PositronEmissionTomography #Neurophysiology #Neuroultrasound

🧠 Good summary by Melvin R. Hayden on the role of blood-brain barrier disruption and dementia progression. The cerebral microbleeds (CMBs) are the known markers of cerebral small vessel disease, reveal a higher risk for strokes and dementia. Utilizing MRI imaging and transmission electron microscopy, several researchers have traced the progression of CMBs, linking them to brain endothelial cell dysfunction and blood-brain barrier disruptions. 🔬 Study Design: The methodology involves detailed MRI imaging to detect CMBs and transmission electron microscopy to observe the ultrastructural changes in brain endothelial cells. 💡 Key findings: 🕐 MRI findings correlated strongly with increased risks of both hemorrhagic and ischemic strokes, emphasizing the importance of CMBs as risk markers. Specific imaging techniques like T2*-weighted gradient recall echo were crucial in identifying the characteristic hypointense (black) lesions of CMBs, enhancing our understanding of their distribution and impact. 🕑 Transmission electron microscopy provided insights into the cellular level changes, showing endothelial cell activation/dysfunction and subsequent blood-brain barrier disruption. These findings help explain the leakage of blood components into brain tissues, potentially leading to further neurological damage. 🕒 The study also highlights the relationship between cerebral microbleeds and systemic factors like hypertension and aging, illustrating how these conditions contribute to the pathophysiology of cerebral small vessel disease. For more details: https://lnkd.in/exukGZiX #Neuroscience #BloodBrainBarrier #Dementia #MRI #

Researchers from UCLA have identified DDL-920, a brain-permeable small molecule that shows promise in increasing γ-oscillations, thus improving cognition and memory in a mouse model of Alzheimer’s disease (AD). This innovative approach targets the γ-aminobutyric acid type A receptors, specifically focusing on the α1β2δ subunits to modulate the activity of PV+INs involved in generating γ-oscillations. Administered orally, DDL-920 successfully restored cognitive impairments in AD model mice, offering hope for future therapeutics aimed at enhancing cognitive performance and working memory through the brain's natural rhythms. #Neuroscience #BrainHealth #AlzheimersResearch #DDL-920

🧠 A new study shows (yet again) the significant role of increased blood-brain barrier (BBB) permeability in the pathogenesis of Alzheimer’s Disease (AD). The research demonstrates how chronic extravasation of bloodborne amyloid-beta (Aβ)42 peptide and brain-reactive autoantibodies, facilitated by a permeable BBB, contribute to cognitive impairments and AD-related pathological changes in a mouse model. 💡 Key findings: 1.   Mice subjected to chronic BBB permeability showed marked deficits in long-term memory retention and heightened susceptibility to cognitive interference, spotlighting the intricate interplay between BBB integrity and cognitive health. 2.   Immunohistochemical analyses revealed an increased influx of Aβ42 and IgG into the brain, with selective binding to neurons. This suggests a crucial pathway through which bloodborne factors contribute to neuronal dysfunction. 3.   The study underscores the potential synergistic effects of BBB compromise and the entry of Aβ42 into the brain in initiating the neuropathological and cognitive changes associated with AD. Check out for more: https://lnkd.in/dKGq6zNr #AlzheimersResearch, #BloodBrainBarrier, #Neuroscience, #CognitiveHealth, #AmyloidBeta, #BrainHealth, #Neurodegeneration