Agents in early development for treatment of bladder dysfunction – promise of drugs acting at TRP channels?

Andersson, Karl Erik

doi:10.1080/13543784.2019.1654994

Cited by 23 publications

(15 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[ 272,273 ] A number of treatments, ranging from medications to surgical interventions, have been developed with the hope of treating this condition. [ 274–278 ] However, due to the fact that neurogenic bladder dysfunction can arise from a number of conditions, including Parkinson's Disease, stroke, brain injury, and multiple sclerosis, developing a universal treatment for this condition remains a challenge. [ 279 ] Neurogenic bladder dysfunction has differing results which can range from an overactive bladder, to difficulty passing urine.…”

Section: Neural Engineeringmentioning

confidence: 99%

Triboelectric Nanogenerators for Therapeutic Electrical Stimulation

et al. 2021

View full text Add to dashboard Cite

Current solutions developed for the purpose of in and on body (IOB) electrical stimulation (ES) lack autonomous qualities necessary for comfortable, practical, and self‐dependent use. Consequently, recent focus has been placed on developing self‐powered IOB therapeutic devices capable of generating therapeutic ES for human use. With the recent invention of the triboelectric nanogenerator (TENG), harnessing passive human biomechanical energy to develop self‐powered systems has allowed for the introduction of novel therapeutic ES solutions. TENGs are especially effective at providing ES for IOB therapeutic systems given their bioconformability, low cost, simple manufacturability, and self‐powering capabilities. Due to the key role of naturally induced electrical signals in many physiological functions, TENG‐induced ES holds promise to provide a novel paradigm in therapeutic interventions. The aim here is to detail research on IOB TENG devices applied for ES‐based therapy in the fields of regenerative medicine, neurology, rehabilitation, and pharmaceutical engineering. Furthermore, considering TENG‐produced ES can be measured for sensing applications, this technology is paving the way to provide a fully autonomous personalized healthcare system, capable of IOB energy generation, sensing, and therapeutic intervention. Considering these grounds, it seems highly relevant to review TENG‐ES research and applications, as they could constitute the foundation and future of personalized healthcare.

show abstract

Section: Neural Engineeringmentioning

confidence: 99%

Triboelectric Nanogenerators for Therapeutic Electrical Stimulation

et al. 2021

View full text Add to dashboard Cite

show abstract

“…In contrast, phosphodiesterase type 5 inhibitors, and the substance P and calcitonin gene‐related peptide release inhibitor, cizolirtine, were found to be effective and safe in phase II clinical studies, but not pursued further; a specific response subset of patients has not been identified for any of them. Thus, reawakening an interest of major pharmaceutical companies in OAB might only occur when academic research identifies not only potential therapeutic targets, but also biomarkers to identify patient populations in which responsiveness to addressing these targets is markedly enriched, and translational animals models for such pathophysiology‐defined subsets (Table ) . An example of this could be nerve growth factor, but the evidence for this or other urinary markers at present is insufficiently robust to identify patient populations in which novel treatments might have greater efficacy than existing treatments …”

Section: Future Research Needsmentioning

confidence: 99%

“…Thus, reawakening an interest of major pharmaceutical companies in OAB might only occur when academic research identifies not only potential therapeutic targets, but also biomarkers to identify patient populations in which responsiveness to addressing these targets is markedly enriched, and translational animals models for such pathophysiology-defined subsets ( Table 3). [39][40][41] An example of this could be nerve growth factor, 53 but the evidence for this or other urinary markers at present is insufficiently robust to identify patient populations in which novel treatments might have greater efficacy than existing treatments. 54…”

Section: Future Research Needsmentioning

confidence: 99%

“…These include modulators of various types of K + channels, rho kinase, neurokinin receptors and nitric oxide synthase/guanylyl cyclase . More recently proposed targets include P2X3 receptors, various members of the transient receptor potential family including TRPV1, TRPV4, TRPA1, TRPM4 and TRPM8, and components of the endocannabinoid system, such as fatty acid amide hydrolase . Furthermore, accumulating evidence from animal and patient studies points to a role of atherosclerosis as a predisposing or even causative factor in the development of OAB .…”

Section: Hurdles To Drug Development In Oabmentioning

confidence: 99%

See 1 more Smart Citation

Where will the next generation of medical treatments for overactive bladder syndrome come from?

Michel

2020

Int J of Urology

View full text Add to dashboard Cite

This review article discusses the medical need for improved medical treatments of overactive bladder syndrome, and the hurdles and research required to address that need. Currently, few overactive bladder syndrome patients stay on long‐term treatment, largely because efficacy expectations are not met, and tolerability is considered insufficient for the chronic treatment of a non‐life‐threatening condition. Therefore, a medical need exists for improved tolerability and, even more importantly, improved efficacy. It is unlikely that major improvements of efficacy and tolerability can be achieved within the currently approved drug classes. Work in experimental animals suggests that many causes of overactive bladder syndrome exist – each with a distinct pathophysiology. This makes it unlikely that a single medication can address the pathophysiology and treatment needs of all overactive bladder syndrome patients; accordingly, any medication will appear to have only moderate efficacy in the overall group of overactive bladder syndrome patients, even if it fully eliminates symptoms within a subset of patients. It is proposed that only identification of subsets of patients with a defined pathophysiology (and biomarkers thereof) will allow the development and use of targeted treatment that can be highly effective in such subsets.

show abstract

“…Особливу увагу приділяють каналам транзієнтного рецепторного потенціалу (TRP), що експресуються в епітеліальних, нервових і гладеньком'язових клітинах (ГМК). У багатьох наукових роботах показано їх участь у регуляції судинного тонусу, моторики кишечника, скоротливості сечового міхура та матки, проте механізми активації цих каналів вивчені недостатньо [3]. Відсутність такої ключової інформації відкриває перспективу подальшої роботи в цьому напрямі, спрямовуючи її у фокус актуальних клінічних проблем.…”

unclassified

Ion channels in a context of the development of new molecular targets for regulation of uterine contractions

et al. 2020

View full text Add to dashboard Cite

Many women now have complications in childbirth due to poor labor, which often threatens both mother and fetus. Also,the problem of prevention and treatment of premature uterine contractions is unresolved. Therefore, in this work we investigated the influence of ion channels as the end stage effectors of the regulatory cascades in the contractility of myometrium. To better understand the participation of TRPC4, TRPV4 and BKCa ion channels in myometrial contractility, we conducted experiments, keeping in mind the fact that changes in ionic conductivity of the plasma membrane regulate spontaneous and agonist-induced contractions. On the myometrial preparations of pregnant rats usingisolated tissue tensiometry, the amplitude of contractile force was recorded under the activation of these ion channels by their selective agonists. Obtained results allow us to consider (-) – englerin A as a way to stimulate uterine contractions in case of insufficient response to oxytocin, because at a concentration of 1 nM a significant increase in contraction force was developed and did not differ statistically from the response to oxytocin or carbacholin. The use of an agonist at concentrations of 30-100 nM causes some suppression of contractility. Based on the results describing the role of TRPV4 channels, namely the reduction of uterine smooth muscle contractions in response to their selective agonist GSK1016790A administration, we suggest that the main effect of activation of these channels depends on the expression and activity of adjacent calcium-dependent potassium channels. Our experiments found that the use of the liposomal form of quercetin to activate BKCa channels inhibits the excitability of myometrial cells more effectively than that dissolved in DMSO, which is promising for the correction of premature or excessive uterine activity.

show abstract

Agents in early development for treatment of bladder dysfunction – promise of drugs acting at TRP channels?

Cited by 23 publications

References 67 publications

Triboelectric Nanogenerators for Therapeutic Electrical Stimulation

Triboelectric Nanogenerators for Therapeutic Electrical Stimulation

Where will the next generation of medical treatments for overactive bladder syndrome come from?

Ion channels in a context of the development of new molecular targets for regulation of uterine contractions

Contact Info

Product

Resources

About