Incorporating Natural Products, Pharmaceutical Drugs, Self-Care and Digital/Mobile Health Technologies into Molecular-Behavioral Combination Therapies for Chronic Diseases
Abstract:Abstract:Merging pharmaceutical and digital (mobile health, mHealth) ingredients to create new therapies for chronic diseases offers unique opportunities for natural products such as omega-3 polyunsaturated fatty acids (n-3 PUFA), curcumin, resveratrol, theanine, or α-lipoic acid. These compounds, when combined with pharmaceutical drugs, show improved efficacy and safety in preclinical and clinical studies of epilepsy, neuropathic pain, osteoarthritis, depression, schizophrenia, diabetes and cancer. Their addi… Show more
“…Positive data from clinical studies of digital technologies for the treatment of pain suggest an emergence of "digital analgesics" (11,13,14). Using digital therapeutics to deliver non-pharmacological interventions such as music and/or physical exercise creates new opportunities for combining these modalities with pharmacotherapies and clinicallyvalidated natural products (4)(5)(6). While development of digital therapeutics does not require preclinical testing (in contrast to regulatory requirements for investigational new drug (IND) enabling studies), translational implications of our study include: (1) using EE as a preclinical surrogate for testing combinations of non-pharmacological modalities for the treatment of pain and other chronic diseases, and (2) preclinical testing and FIGURE 8 | Working model of mechanisms by which musical compositions can exert their analgesic and anticonvulsant activities.…”
Section: Translational Implications Of Studying Enriched Environmentmentioning
confidence: 99%
“…To innovate treatments for neurological disorders, we have been studying diverse strategies to integrate digital health technologies with CNS drugs (4)(5)(6). Digital health is a branch of healthcare that employs internet, digital, and mobile technologies for improving health and/or treating diseases.…”
Digital therapeutics (software as a medical device) and mobile health (mHealth) technologies offer a means to deliver behavioral, psychosocial, disease self-management and music-based interventions to improve therapy outcomes for chronic diseases, including pain and epilepsy. To explore new translational opportunities in developing digital therapeutics for neurological disorders, and their integration with pharmacotherapies, we examined analgesic and antiseizure effects of specific musical compositions in mouse models of pain and epilepsy. The music playlist was created based on the modular progression of Mozart compositions for which reduction of seizures and epileptiform discharges were previously reported in people with epilepsy. Our results indicated that music-treated mice exhibited significant analgesia and reduction of paw edema in the carrageenan model of inflammatory pain. Among analgesic drugs tested (ibuprofen, cannabidiol (CBD), levetiracetam, and the galanin analog NAX 5055), music intervention significantly decreased paw withdrawal latency difference in ibuprofen-treated mice and reduced paw edema in combination with CBD or NAX 5055. To the best of our knowledge, this is the first animal study on music-enhanced antinociceptive activity of analgesic drugs. In the plantar incision model of surgical pain, music-pretreated mice had significant reduction of mechanical allodynia. In the corneal kindling model of epilepsy, the cumulative seizure burden following kindling acquisition was lower in animals exposed to music. The music-treated group also exhibited significantly improved survival, warranting further research on music interventions for preventing Sudden Unexpected Death in Epilepsy (SUDEP). We propose a working Metcalf et al. Music-Enhanced Analgesic and Antiseizure Activities model of how musical elements such as rhythm, sequences, phrases and punctuation found in K.448 and K.545 may exert responses via parasympathetic nervous system and the hypothalamic-pituitary-adrenal (HPA) axis. Based on our findings, we discuss: (1) how enriched environment (EE) can serve as a preclinical surrogate for testing combinations of non-pharmacological modalities and drugs for the treatment of pain and other chronic diseases, and (2) a new paradigm for preclinical and clinical development of therapies leading to drug-device combination products for neurological disorders, depression and cancer. In summary, our present results encourage translational research on integrating non-pharmacological and pharmacological interventions for pain and epilepsy using digital therapeutics.
“…Positive data from clinical studies of digital technologies for the treatment of pain suggest an emergence of "digital analgesics" (11,13,14). Using digital therapeutics to deliver non-pharmacological interventions such as music and/or physical exercise creates new opportunities for combining these modalities with pharmacotherapies and clinicallyvalidated natural products (4)(5)(6). While development of digital therapeutics does not require preclinical testing (in contrast to regulatory requirements for investigational new drug (IND) enabling studies), translational implications of our study include: (1) using EE as a preclinical surrogate for testing combinations of non-pharmacological modalities for the treatment of pain and other chronic diseases, and (2) preclinical testing and FIGURE 8 | Working model of mechanisms by which musical compositions can exert their analgesic and anticonvulsant activities.…”
Section: Translational Implications Of Studying Enriched Environmentmentioning
confidence: 99%
“…To innovate treatments for neurological disorders, we have been studying diverse strategies to integrate digital health technologies with CNS drugs (4)(5)(6). Digital health is a branch of healthcare that employs internet, digital, and mobile technologies for improving health and/or treating diseases.…”
Digital therapeutics (software as a medical device) and mobile health (mHealth) technologies offer a means to deliver behavioral, psychosocial, disease self-management and music-based interventions to improve therapy outcomes for chronic diseases, including pain and epilepsy. To explore new translational opportunities in developing digital therapeutics for neurological disorders, and their integration with pharmacotherapies, we examined analgesic and antiseizure effects of specific musical compositions in mouse models of pain and epilepsy. The music playlist was created based on the modular progression of Mozart compositions for which reduction of seizures and epileptiform discharges were previously reported in people with epilepsy. Our results indicated that music-treated mice exhibited significant analgesia and reduction of paw edema in the carrageenan model of inflammatory pain. Among analgesic drugs tested (ibuprofen, cannabidiol (CBD), levetiracetam, and the galanin analog NAX 5055), music intervention significantly decreased paw withdrawal latency difference in ibuprofen-treated mice and reduced paw edema in combination with CBD or NAX 5055. To the best of our knowledge, this is the first animal study on music-enhanced antinociceptive activity of analgesic drugs. In the plantar incision model of surgical pain, music-pretreated mice had significant reduction of mechanical allodynia. In the corneal kindling model of epilepsy, the cumulative seizure burden following kindling acquisition was lower in animals exposed to music. The music-treated group also exhibited significantly improved survival, warranting further research on music interventions for preventing Sudden Unexpected Death in Epilepsy (SUDEP). We propose a working Metcalf et al. Music-Enhanced Analgesic and Antiseizure Activities model of how musical elements such as rhythm, sequences, phrases and punctuation found in K.448 and K.545 may exert responses via parasympathetic nervous system and the hypothalamic-pituitary-adrenal (HPA) axis. Based on our findings, we discuss: (1) how enriched environment (EE) can serve as a preclinical surrogate for testing combinations of non-pharmacological modalities and drugs for the treatment of pain and other chronic diseases, and (2) a new paradigm for preclinical and clinical development of therapies leading to drug-device combination products for neurological disorders, depression and cancer. In summary, our present results encourage translational research on integrating non-pharmacological and pharmacological interventions for pain and epilepsy using digital therapeutics.
“…Microbial secondary metabolites with widely divergent chemical structures have been regarded not only as prolific drug candidates, but also an inspiration for the starting point of drug design [1]. For half a century, antibiotics derived from microorganisms have become the leading drugs in different clinical fields due to their distinct structures and excellent activities [2,3]. However, the emerging of drug-resistant bacteria and drug-resistant tumors has prompted people to search for new drugs and novel mechanisms of action [4,5].…”
Section: Introductionmentioning
confidence: 99%
“…shell-016 from the Binzhou shell dike island was studied. Four new polyketides, named shellmycin A-D (1)(2)(3)(4), containing the tetrahydroanthra-γ-pyrone skeleton, were isolated ( Figure 1). The structures and relative configurations of the compounds were elucidated by NMR and high-resolution mass spectrometry (HR-MS).…”
Four novel bioactive tetrahydroanthra-γ-pyrone compounds, shellmycin A–D (1–4), were isolated from the marine Streptomyces sp. shell-016 derived from a shell sediment sample collected from Binzhou Shell Dike Island and Wetland National Nature Reserve, China. The structures of these four compounds were established by interpretation of 1D and 2D NMR and HR-MS data, in which the absolute configuration of 1 was confirmed by single crystal X-ray diffraction, and compound 3 and 4 are a pair of stereoisomers. Compound 1–4 exhibited cytotoxic activity against five cancer cell lines with the IC50 value from 0.69 μM to 26.3 μM. Based on their structure–activity relationship, the putative biosynthetic pathways of these four compounds were also discussed.
“…Multiple studies correlate treatment with different antioxidants with inhibition of pro-inflammatory gene expression and increased expression of antiinflammatory genes (11). Concerning resveratrol, a natural non-flavonoid polyphenolic compound, its being related to healthy habits (12). Moreover, emerging evidence on its implication in a number of pathophysiological processes like cancer (13), cardiovascular diseases (14), or inflammatory diseases (15) are arising.…”
SummaryBackground. Atopic Dermatitis (AD) is a common, chronic skin disorder caused by complex genetic, immunological, and environmental interactions. The current standard treatments for AD are improvable with a low efficiency, particularly in severe cases. Using well characterized molecules the "Ignacio Umbert Dermatology Institute" (IUDI) has developed topical treatments differentiated from the standards (European patent number EP2311454). Objective. Evaluate the therapeutic efficacy of EP2311454 treatment in AD patients and its antiinflammatory effect in vitro. Materials and methods. Using a cellular model for human macrophages (THP-1 cell line) the principal components of EP2311454 treatment was evaluated. Expression of proinflammatory cytokines was measured through RNA quantification and ELISA technique. Therapeutically EP231154 treatment was tested in forty three AD patients and SCORing Atopic Dermatitis (SCORAD) and Dermatology Quality of Life Index (DLQI) was evaluated before and after the treatment. Results. The effect was significantly anti-inflammatory towards IL6 and COX2. The therapeutic efficacy was demonstrated by obtaining a reduction of initial SCORAD levels in the 97,7% of patients besides EP2311454 treatment reduces DLQI significantly.
Conclusions.Clinically, EP2311454 treatment is effective, especially in severe cases, getting a reduction of 80% initial levels at the end of the evaluation period. Moreover, the effect was detected from the first week.
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