Neurodegeneration and chronic pain are significant medical problems that ensue from activation of the innate immune system chemokine receptors. Our latest advances deliver oral peptides (RAPs) that safely block chemokine receptors such as CCR5, to block and reverse neurodegeneration. CPB’s platform consists an array of small molecule receptor-active peptides that are oral and safe. These peptides are being targeted to treat chronic pain, Alzheimer’s, and Parkinson’s diseases. These same chemokine receptor pathways are being shown to control reward pathways and animal drug-seeking behaviors. Blocking them is opening a new frontier for treating opioid and other substance abuse disorders.
Chronic inflammation in the human body is the cause for a wide variety of seemingly unrelated conditions ranging from degeneration of neurons and loss of synapses in the brain during cognitive decline in aging, traumatic brain injuries, and nerve damage resulting in chronic pain as occurs in diabetic peripheral neuropathy, to metabolic diseases like NASH, and skin conditions including psoriasis. In the CNS a persistent innate immune response activates microglia which cause synapse loss leading to cognitive decline in diseases including Alzheimer’s and Parkinson’s, or loss of function in brain injury and stroke, as well as nerve damage in chronic pain conditions like diabetic peripheral neuropathy. We are developing receptor-active peptides (“RAPs”) that block specific chemokine receptors (CCR2/CCR5/CCR8/CXCR4) of the innate immune system to normalize the excessive microglial, chemokine and cytokine responses that underlie disparate conditions that share a common neurodegenerative inflammatory pathogenesis. Blocking CCR5 promotes synaptogenesis to reverse nerve damage in neuropathic pain, improve cognition in neuro-AIDS, and promotes motor recovery in Parkinson’s Disease, brain injury and stroke.
Antagonists of the innate immune chemokine receptor CCR5, first shown with the octapeptide Peptide T, have improved cognition ( Heseltine 1998; D’Antoni, 2018) and functional PET imaging (Villemagne, 1996) in neuro-AIDS. CCR5 has recently been shown to be a therapeutic target in brain injury and stroke (Joy, 2019), actions also shared by Peptide T (Li, 2016) and to improve motor function in Parkinson’s Disease (Mondal, 2019).
Creative Bio-Peptides is developing synapse protecting and restoring treatments for the 5.8M Americans (2019) who are living with Alzheimer’s (AD), Parkinson’s (PD) and other dementias, their caregivers, and families. Our safe and rapidly brain entering new oral peptides block activation of select chemokine receptors of the innate immune system that lead to early synapse loss, the principal cause of memory and cognitive decline in various dementias and normal aging. We seek to deliver a safe and effective intervention to protect and restore synapses in order to prevent, potentially even reverse, cognitive declines in dementias.
Our focus is the next generation oral analogs of the clinically successful non-oral Peptide T (aka “DAPTA”) with better brain entry and greatly enhanced stability, suitable for a 1x/day oral pill formulation. Our receptor-active peptides (“RAPs”) balance the dysregulated innate immune chemokine and cytokine responses that underlie many neurodegenerative diseases to promote disease modifying neuro-regeneration and synapse reconstitution . Our lead candidate is R103 (aka RAP-103), in development to treat neuropathic pain and dementias.