Walden Bjørn-Yoshimoto
Assistant Professor, University of Copenhagen
Every year, more than 30 million Americans are prescribed medications for pain relief, reflecting the extensive pain management needs across the country and indeed the world. Among these prescriptions, opioids account for more than half, despite their well-documented downsides. In addition to acute pain conditions, opioids are frequently dispensed for persistent pain, including conditions like neuropathic pain, where their efficacy is inconsistent at best. This widespread use, despite the substantial risks of addiction and adverse effects including respiratory depression, constipation, confusion, and emesis, underscores the desperate need for alternatives.
We recently discovered that some fish-hunting cone snails (marine mollusks) produce peptide toxins, called ‘consomatins’, that were recruited and evolved from their endogenous somatostatin-like signaling system. From in silico and in vitro screenings, we identified consomatin Fj1 as a potent and selective agonist at the somatostatin receptor 4 (SSTR4). This receptor has recently emerged as a promising target for treating various peripheral pain conditions by blocking the conveyance of nociceptive information from the periphery to the central nervous system (CNS). Selective activation of the SSTR4 is expected to circumvent the known endocrine side effects associated with broader SSTR activation. Studies in rodent models indicate that SSTR4 activation is effective at treating a range of pain indications, and a phase 2 trial for diabetic peripheral neuropathic pain has recently provided clinical target validation. Here, we report on Fj1's efficacy in alleviating pain in rodent models of postoperative and peripheral neuropathic pain. We further show that Fj1 does not penetrate the CNS, and finally that Fj1 is amenable to modifications that significantly enhance the potency, highlighting its potential as a novel analgesic peptide therapeutic.
Walden Bjørn-Yoshimoto did his BSc and MSc in biochemistry at the University of Copenhagen (Denmark), where his thesis work focused on intracellular trafficking of the dopamine transporter in the lab of Prof. Ulrik Gether. He obtained his PhD in pharmaceutical sciences, where he studied the molecular pharmacology of excitatory amino acid transporters (EAATs) in the lab of Assoc. Prof. Anders A. Jensen, where he identified and developed the most EAAT3-selective tool compound to date. He did a short post-doc in the same lab, investigating molecular determinants of binding selectivity of G protein coupled (GPCR) serotonin receptor ligands. Subsequently, he moved to the lab of Assoc. Prof. Helena Safavi at the department of Biomedical Sciences to study cone snail peptides (conopeptides, conotoxins); in particular, conopeptides with activity at human GPCRs as novel drug leads. With a broad background in biochemistry, molecular pharmacology, and toxinology, his independent research focuses on novel discovery pipelines for GPCR-modulating peptide toxins as drug leads, as well as development of a lead for the treatment of peripheral neuropathy and postoperative pain.