Jacqueline Sagen, Ph.D., M.B.A.
Cell Transplantation and Gene Therapies for Alleviation of Chronic Pain
Chronic pain, such as that resulting from SCI or other injuries to the nervous system, is difficult to manage clinically and contributes to reduced quality of life and productivity. In addition, the presence of untreated pain can interfere with the ability to fully participate in rehabilitative strategies, thus limiting potential long-term gains in functional recovery. Pain due to injury to the nervous system is difficult to treat and pharmacological options for patients are marginally effective in the long term and fraught with unacceptable side effects and potential tolerance and addiction. Our laboratory continues to explore novel and more effective strategies in the therapeutic management of chronic pain and reduced reliance on opioids. Gene therapy, either via direct delivery to the nervous system or via cell transplantation, can provide a sustained and renewable source of pain-reducing agents at circumscribed nervous system sites, avoiding off-target side effects as well as potentially reversing underlying neuropathology. The overall goal of this research is to achieve improved and more permanent chronic pain alleviation by providing synergistic naturally-derived analgesic molecules to restore spinal inhibitory processes and reduce abnormal hyperexcitability using targeted gene therapies.
The focus of recent work in our lab include the NMDA antagonist peptide, serine-histogranin (SHG), CGRP antagonist peptide CGRP8-37, and cone snail derived peptides. We are designing and evaluating multimeric and combination constructs for gene therapies in models of neuropathic pain. In addition, the use of regulatable systems is being explored, particularly for potential regulation of analgesic transgene expression in response to endogenous inflammation associated with injury. A second ongoing project in our lab is to develop intensive locomotor training as an adjunct therapy that attenuates SCI pain symptoms and may provide complementary beneficial outcomes in combination with other treatments. A third key undertaking in our lab is the design and assessment of more clinically relevant behavioral models for chronic pain syndromes including SCI below-level neuropathic pain, phantom limb pain, and post-traumatic headache, that can provide better predictive validity for clinical translation.
Our current research initiatives and future challenges include: (1) Design of synergistic combination analgesic gene constructs for cell transplantation or viral vector-based delivery, (2) Discovery and characterization of novel mammalian and non-mammalian peptides (e.g. cannabinoid-acting conopeptides) that can be developed for long-term chronic pain management, (3) Addition of exercise training to enhance analgesic benefits and overall well-being, (4) Synthesis of regulatable gene constructs to produce engineered analgesic peptides in response to inflammation and pain, and (5) Exploration of emerging technologies such as gene editing to improve cell and tissue transplantability.