System and apparatus for genetic regulation by electromagnetic stimulation fields
Inventors
Goodwin, Thomas J. • Shackelford, Linda C.
Assignees
National Aeronautics and Space Administration NASA
Publication Number
US-10724030-B2
Publication Date
2020-07-28
Expiration Date
2030-10-07
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Abstract
The present invention provides a system for delivering a time-varying stimulation field to a subject. In the system, a power source, a control component and a transmission component operate as a stimulation field generator to provide a predetermined time-varying stimulation field to up-regulate or down-regulate an expression level of human genes. The present invention also provides a wearable apparatus for delivering the time-varying magnetic field to mammalian cells associated with bone formation in a subject. The wearable apparatus contains the stimulation field generator in a housing. The resulted modification on gene regulation of these genes and mammalian cells promotes the retention, repair of and reduction of compromised mammalian cartilage, bone, and associated tissue.
Core Innovation
The present invention provides a system and method for modifying the genetic regulation of mammalian chondrocytes, osteoblasts, osteocytes, osteoclasts, nucleus pulposus, and associated tissue by delivering a tuned time-varying stimulation field of predetermined profile. This tuning includes controlling performance characteristics such as B-Field magnitude, frequency, wavelength, rise and fall times, slew rates, duty cycle, and exposure times to preferentially stimulate gene activation responsible for the regeneration, repair, maintenance, and modification of bone and cartilage tissues.
The invention is embodied in an apparatus comprising a power source, a control component, and a transmission component to generate and deliver the electromagnetic stimulation field in a wearable form factor to a targeted region of interest. The field profile can be empirically tuned using bioreactor systems with human chondrocytes and osteoblast cells to optimize anabolic or catabolic genetic responses as required for various therapeutic goals.
The problem solved relates to the limitations of current therapies for cartilage and bone diseases such as osteoarthritis and osteoporosis, which are often invasive or nonspecific electrical or magnetic stimulation methods. Existing therapies inadequately address gene-specific regulation and tissue restoration without invasive procedures. Additionally, prior art focuses mainly on magnetic field magnitude, leading to insufficient control of the biological effects. The invention overcomes these by providing specific stimulation field profiles to control gene expression non-invasively and selectively.
Claims Coverage
The patent claims are centered on a wearable apparatus for delivering a tuned time-varying magnetic field to bone formation cells in humans, incorporating multiple inventive features related to the stimulation field and apparatus components.
Wearable apparatus comprising a stimulation field generator
The apparatus includes a power source, control component, and transmission component within a housing configured to deliver a tunable time-varying magnetic field to cells associated with bone formation.
Delivery of time-varying magnetic field with predetermined performance characteristics
The stimulation field generator provides a magnetic field in the form of a substantially square, biphasic waveform with specific parameters such as B-Field magnitude (0.05 G to 12 G), rising slew rate (2.0 kG/s to 4.5 kG/s), rise/fall times (125 μs to 1 ms), falling slew rate (2.0 kG/s to 500.0 kG/s), frequency (1 Hz to 20 Hz), wavelength, and duty cycle (65% to 80%) targeted for gene activation.
Control component configured for adjustment of stimulation field profiles
The control component is configured to adjust at least one predetermined profile of the magnetic field, including parameters such as B-Field magnitude, rising and falling slew rates, rise and fall times, frequency, wavelength, and duty cycle for tuning gene activation effects.
Activation of specific genes in human chondrocyte cells
The stimulation field activates a range of genes in human chondrocytes including Wnt signaling, forkhead box, sex determining region Y Sry, parathyroid hormone, transforming growth factor beta super family, integrin, interleukin, thrombospondin, laminin, proteoglycan, collagen, insulin, disintegrin and metalloproteinase, actin, catenin, and cadherin super genes.
Activation of specific genes in human osteoblast cells
The stimulation field activates specific genes in human osteoblasts including forkhead box, parathyroid hormone, integrin, interleukin, thrombospondin, laminin, proteoglycan, osteoglycin, collagen, insulin, disintegrin and metalloproteinase with thrombospondin motifs, matrix metallopeptidase, actin, catenin, cadherin super genes, B-cell lymphoma, calmodulin calcium-modulated, calumenin, cathepsin, clusterin, cytochrome P450 super gene, endoglin, fibrillin, fibroblast growth factor, leptin, mitogen-activated protein kinases, muscle segment homeobox, neurogenic locus notch homolog, peroxisome proliferator-activated receptors, platelet derived growth factor, reticulocalbin, runt related transcription factors, signal transducer activator of transcription, similar to mothers against decapentaplegic, stanniocalcin, superoxide dismutase, syndecan, tumor necrosis factor super gene, AKT/protein kinase B signaling, and importin genes.
The claims collectively define a wearable apparatus producing a specifically tunable time-varying magnetic field with precise electrical and magnetic parameters to selectively activate genes involved in bone and cartilage formation in human cells by employing a system comprised of a power source, control unit, and transmission component within a housing.
Stated Advantages
Provides a completely non-invasive method to modulate gene expression in cartilage, bone, and associated tissues for therapeutic purposes.
Enables tuning of multiple stimulation field parameters beyond just magnetic field magnitude, allowing selective up-regulation or down-regulation of specific genes.
Facilitates customized therapeutic applications by combining stimulation fields to promote anabolic and catabolic effects in a controlled sequence.
Uses wearable apparatus allowing targeted delivery of stimulation fields to a region of interest, improving patient compliance and treatment specificity.
Optimizes genetic anabolic and catabolic responses by linking physical field parameters with sub-cellular molecular changes in the target cells.
Documented Applications
Treatment of cartilage and bone diseases including osteoarthritis, osteoporosis, and osteopenia.
Promotion of retention, repair, regeneration, and reduction of compromised cartilage, bone, and associated tissue in mammalian systems.
Use as a therapeutic device for tissue regeneration in human subjects by activating specific gene families related to tissue growth.
Neuromuscular stimulation for reducing muscle atrophy as a countermeasure to body unloading effects in environments such as hospitals or human spaceflight.
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