Kenneth Madsen's Colleagues at DolorestBio
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DolorestBio
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Development of new drugs to treat chronic pain.At DolorestBio, we aim to provide better treatment for patients suffering from Chronic Pain conditions thereby addressing a vast unmet medical need.We are developing innovative peptide and gene therapeutic-based solutions to selectively target the neural adaptations underlying chronic pain thereby circumventing dose-limiting side-effects.The ProblemNeuropathic pain affects 7–10% of the world population with higher prevalence in women and elderly. Current medication, including anti‐epileptics, antidepressants, and opioids, provides only partial pain relief and comes with considerable side effects. Consequently, there is an urgent need for better treatment.The causes for development of neuropathic pain include diabetes mellitus, treatment with chemotherapeutics, and herpes zoster, which all cause damage to the peripheral nervous system leading to increased central pain perception. This central sensitization involves insertion of excess glutamate receptors in the dorsal horn synapse, and direct modulation of the glutamatergic transmission by glutamate receptor antagonist to obtain better efficacy has been pursued, but clinical development has been discontinued due to adverse side effects.Our SolutionWe have refined the effort to modulate this synaptic transmission in the spinal cord by specifically targeting the scaffold protein PICK1, which is responsible for insertion of excess glutamate receptors in the hyper‐sensitized condition rather than blocking the receptors themselves.We have developed a synthetic bivalent peptides that inhibits PICK1 with high specificity and selectivity. Moreover, we have developed a gene therapeutic approach enabling neuron-specific expression of the bivalent peptide. The mechanism of action is supported by demonstration of reduced insertion of calcium permeable AMPA receptors in spinal cord tissue and by electrophysiological in vivo measurement in injured animals