Xalud Therapeutics proposes to evaluate the applicability of its novel and potent anti-inflammatory therapy, XT-101, for the treatment of motor impairment, gait disorders, and neuropathic pain in degenerative and inflammatory autoimmune rodent models of multiple sclerosis (MS). XT-101 is a non-viral form of gene therapy that causes the meningeal cells surrounding the spinal cord to secrete the powerful, natural, anti- inflammatory interleukin-10 (IL-10). Based on extensive pre-clinical research, Xalud believes that the secreted IL-10 will reduce inflammation and normalize the pathological microglia and astrocyte activity that is seen in MS. Xalud proposes to study XT-101 in both inflammatory and neurodegenerative rodent models of MS and to conduct various cell and tissue analyses to better understand and elucidate the biological effects of XT-101. Xalud expects to demonstrate in these models that XT-101 reduces motor impairment, alleviates gait disorders and resolves neuropathic pain. Xalud also expects that XT-101 will have a positive effect on numerous elements of MS pathology including: immune cell infiltration, inflammation, reduced glutamate transport, demyelination, and neuronal apoptosis. Support of the proposed studies would greatly accelerate the development of XT-101 for clinical applications. Xalud is currently conducting IND-enabling toxicology studies for the use of XT-101 in neuropathic pain and expects to file an IND in late 2013. The additional efficacy data provided by the proposed studies would support the initiation of human trials of XT-101 in neuropathic pain, gait disorders and possibly other MS-related indications. Xalud believes that XT-101, if successfully developed, could have a tremendous impact on the clinical treatment of MS and greatly improve the quality of life MS patients. Neuropathic pain and gait disorders impact almost all MS patients and greatly reduce their ability to participate in society and enjoy life. Further, XT-101 may slow disease progression in the currently untreatable progressive forms of MS. Because the method of action of XT-101 is markedly different from all existing or imminent MS treatments, it has the potential to be an extremely useful addition and complement to current medical practice.
Public Health Relevance Statement: Public Health Relevance: Xalud Therapeutics, Inc. is seeking support to advance the development of XT-101 for the treatment of motor impairment, gait disorders and neuropathic pain associated with multiple sclerosis (MS). Currently, there are no treatments approved for MS-related neuropathic pain or for treating progressive forms of the disease and only one treatment approved for gait disorders. By addressing these areas of tremendous unmet clinical need, Xalud believes XT-101 can greatly improve the quality of life of MS patients.
Project Terms: Address; Advanced Development; Affect; Anti-inflammatory; Anti-Inflammatory Agents; Applications Grants; Area; Astrocytes; Autoimmune Process; base; Biological; Brain; cell type; Cells; Clinical; clinical application; Clinical Research; Clinical Treatment; Clinical Trials; Complement; cytokine; Data; Demyelinations; Development; Disease; Disease Progression; Elements; Employee Strikes; Experimental Autoimmune Encephalomyelitis; Female; Funding; Gait; Gait abnormality; gene therapy; Glutamate Transporter; Glutamates; Goals; Grant; Human; Immune; improved; Infiltration; Inflammation; Inflammatory; Interferons; Interleukin-10; Intrathecal Injections; Life; macrophage; male; Medical; Meningeal; Methods; Microglia; migration; Modeling; Molecular; monocyte; motor impairment; Multiple Sclerosis; Mus; Myelin; National Institute of Neurological Disorders and Stroke; Nerve Degeneration; nerve injury; neuron apoptosis; neuronal survival; Neurons; novel; Pain Disorder; painful neuropathy; Paralysed; Pathology; Patients; Phase; plasmid DNA; Plasmids; pre-clinical research; Production; public health relevance; Quality of life; Radiculopathy; Rattus; Relapse; Relapsing-Remitting Multiple Sclerosis; repaired; Research Design; Rodent Model; Running; Safety; Series; Societies; Spinal; Spinal Cord; Stem cells; Symptoms; T-Cell Activation; Testing; Therapeutic; Tissues; Toxicology
