Translational Neuro-Urology

 

Previous research results:

Our group aims at uncovering the fine mechanism of micturition control in health and in several disease states and at offering better and safer treatments to patients with lower urinary tracts symptoms, like urinary incontinence or bladder pain.

At an experimental level we make use of animal models that mimic diseases as spinal cord lesions, overactive bladder or bladder obstruction due to prostate enlargement. We have studied the importance of neurotrophins and TRP receptors and its endogenous agonists in these processes and in terms of therapeutic possibilities we are making progresses in finding effective TRPV1 and TRPV4 antagonists and clarifying how Botulinum toxin works once injected in the bladder or in the prostate gland.

At a clinical level we were involved in a large multicentre clinical trial that demonstrated for the first time the efficacy and safety of Botulinum Toxin type A in the treatment of urinary incontinence due to neurological disorders and defined the ideal dose of this toxin. We also contributed decisively to introduce this toxin in the treatment of chronic bladder pain states. We made substantial progresses in the definition of urinary biomarkers in overactive bladder. We are currently investigating the possibilities of the pharmacological manipulation of the bladder adrenoreceptors for the treatment of this syndrome. Finally we investigated new surgical options for treatment of urinary incontinence in women.

 

IMAGE: Co-expression of cleaved SNAP-25 (red) with VAChT (green) in a pasympathetic ganglion of the guinea pig bladder following Botulinum toxin injection. The end product of the neurotoxin is localized in cholinergic terminals (yellow). Coelho A, Cruz CD, Cruz F, Avelino A. Journal of Urology, in press

 

Future research goals:

The future research of the translational neuro-urology group will be directed into two main new areas. One is the prevention of bladder overactivity and the other is the identification of urine and blood biomarkers to aid the diagnosis and treatment of bladder overactivity.

Prevention of bladder overactivity will start to be investigated in animals model of spinal cord injury, which most closely reproduce the equivalent human condition (spinal cord lesion). Fast administration of TRP antagonist and sequestration of neurotrophins appear as ideal pharmacological intervention to prevent the appearance of bladder overactivity. In addition we hope to investigate the effect of electrosacral neuromodulation in this process, in collaboration with the Tubingen Group of Neurourology (Germeny). As collateral to this research we expect to gain relevant information about the role of neurotrophins and TRP receptors in micturition control.

Biomarkers are measurable characteristics that reflect physiological, pharmacological, or disease processes.  Bladder overactivity lacks objective diagnostic tests. Therefore, identification of objective parameters will be extremely relevant to aid diagnosis, in addition to clinical examination, and monitor treatment. Although our recent studies indicate that neurotrophins are the most obvious candidates, we intent to perform proteomic analysis of urine and blood of these patients in order to detect additional biomarkes candidates.

 

Selected publications:

Cruz F, Herschorn S, Aliotta P, Brin M, Thompson C, Lam W, Daniell G, Heesakkers J, Haag-Molkenteller C.. Efficacy and Safety of OnabotulinumtoxinA in Patients with Urinary Incontinence Due to Neurogenic Detrusor Overactivity: A Randomised, Double-Blind, Placebo-Controlled Trial. Eur Urol. 2011 Oct;60(4):742-50. Epub 2011 Jul 13

Intraprostatic Silva J, Pinto R, Carvalho T, Botelho F, Silva P, Silva C, Cruz F, Dinis P. botulinum toxin type A administration: evaluation of the effects on sexual function. BJU Int. 2011 Jun;107(12):1950-4

Antunes-Lopes T, Carvalho-Barros S, Cruz CD, Cruz F, Martins-Silva C (2011). Biomarkers in overactive bladder: a new objective and noninvasive tool? Adv Urol. 2011;2011:382431. Epub 2011 May 29.

Cruz CD, Cruz F (2011). Spinal cord injury and bladder dysfunction: new ideas about an old problem. ScientificWorldJournal. 11:214-34.

Charrua A, Avelino A, Cruz F (2011). Modulation of urinary bladder innervation: TRPV1 and botulinum toxin A. Handb Exp Pharmacol. 202):345-74

Oliveira R, Botelho F, Silva P, Resende A, Silva C, Dinis P, Cruz F. Exploratory Study Assessing Efficacy and Complications of TVT-O, TVT-Secur, and Mini-Arc: Results at 12-Month Follow-Up.Eur Urol. 2011 Jan 21. [Epub ahead of print]
 

 

 

 

 

Group Leader
200.jpeg
francisco.cruz@ibmc.up.pt
People
Researchers

Alturas da Silva, João
joao.alturas.silva@ibmc.up.pt

Charrua, Ana
ana.charrua@ibmc.up.pt

Cruz, Célia
celia.cruz@ibmc.up.pt

Pinto, Rui
rui.pinto@ibmc.up.pt

Silva, António Avelino
antonio.silva@ibmc.up.pt

Silva, Carlos
carlos.silva@ibmc.up.pt

PosDocs

Coelho, Ana
ana.coelho@ibmc.up.pt

Phd Students

Lopes, Tiago
tiago.lopes@ibmc.up.pt

Oliveira, Raquel Leal
raquellmmoliveira@gmail.com


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