Gene therapy for lower urinary tract dysfunction

Abstract

Abbreviations & Acronyms AAV1 = adeno-associated virus type 1 BOO = bladder outlet obstruction DRG = dorsal root ganglion GABA = g-aminobutyric acid GAD = glutamic acid decarboxylase HGF = hepatocyte growth factor HSV = herpes simplex virus IC/BPS = interstitial cystitis/bladder pain syndrome IL = interleukin LUT = lower urinary tract LUTS = lower urinary tract symptoms MnSOD = manganese superoxide dismutase NGF = nerve growth factor POMC = pro-opiomelanocortin SERCA = sarco/endoplasmic reticulum calcium ATPase SR = sarco/endoplasmic reticulum SUI = stress urinary incontinence TNFa = tumor necrosis factor a TNFasR = tumor necrosis factor a soluble receptor Abstract: Lower urinary tract dysfunction is caused by functional and pathophysiological alterations of the peripheral organs, including the urothelium and detrusor smooth muscle, as well as peripheral and central nervous systems. Recent research in this field has increased our understanding of the mechanisms of lower urinary tract dysfunction, and new drugs have been developed, leading to increased treatment options and changing medical care for lower urinary tract symptoms. Nevertheless, clinicians still often experience refractory and treatment-resistant cases against conventional therapeutic modalities. For such cases, gene therapy targeting for the lower urinary tract and its afferent pathway is anticipated to offer a new therapeutic approach. Therefore, in this article, we review the possibility and current status of gene therapy for lower urinary tract dysfunction.

Constipation is reduced by beta-blockers and increased by dopaminergic medications in Parkinson's disease

“…Constipation has been previously associated with urinary dysfunction and symptoms of detrusor hyperactivity, such as urgency and nocturia, in PD patients [26]. Abnormal noradrenergic activity may explain bladder hyperactivity [27], which is exacerbated by both levodopa and dopamine agonists [28], similar to what has been observed in our study for constipation. The association between constipation and OH, another symptom of sympathetic nervous system impairment [29], was also previously reported in PD patients and may be exacerbated by levodopa [18].…”

Intravesical Resiniferatoxin for the Treatment of Storage Lower Urinary Tract Symptoms in Patients with Either Interstitial Cystitis or Detrusor Overactivity: A Meta-Analysis

“…Although treatments have been developed for a long time, urologists still often experience refractory and treatment-resistant patients on whom current therapies have very limited effects [2], [3], [36]. In recent years, several novel approaches with potential benefit for patients, including psychosocial, behavioral, physical and oral treatments, intravesical treatment, electric neuromodulation, reconstructive surgery, and gene therapy, have been clinically used [3], [15], [36]. Systematic review should be performed to fully evaluate the effect of each of these approaches and to provide important evidence for best-practice decisions in these patients.…”

Pelvic Autonomic Neuromonitoring

“…However, brain stem, hypothalamic, and forebrain sites actuating genital engorgement, sexual positioning/posturing, copulatory activity, and ejaculation/orgasm (or its delay) seem more to participate in an evolving and inevitable cascade of events once higher centers have imagined, initiated, consented, and committed to the behavior (Fitzgerald and Mueller, 2004;Yang and Jiang, 2009;Yoshimura and Chancellor, 2003). Distinctive and opposed medial ("M") and lateral ("L") pontine reticular formation sites have been identified for bladder storage/continence and micturition, respectively.…”