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Perspectives on the Urological Care in Parkinson’s Disease Patients - Beyond the Abstract

Parkinson's disease (PD) is recognized as the most common neurodegenerative disorder after Alzheimer's disease. Lower urinary tract symptoms are common in patients with PD, either storage symptoms (overactive bladder symptoms or OAB) or voiding symptoms. Pharmacologic interventions especially anticholinergic medications are the first-line option for treating OAB in patients with PD. Intra-detrusor Botulinum toxin injections, and electrical stimulation were also used to treat OAB in those patients with variable efficacy. Mirabegron is a β3-agonist that can also be used for OAB with superior tolerability to anticholinergics. Desmopressin is effective for the management of nocturnal polyuria which has been reported to be common in PD. Deep brain stimulation surgery is effective in improving urinary functions in PD patients.1


Numerous preclinical and clinical studies have demonstrated that stem-cell (SCs) therapy was of great potential to treat neurogenic bladder dysfunction. The mechanism of bladder recovery is a restoration including cell differentiation, paracrine activity of SCs, and interaction with microenvironment signals.2 SCs may secrete many growth factors, including hepatic growth factor, nerve growth factor, brain-derived growth factor, glial-derived growth factor, insulin-like growth factor, vascular endothelial growth factor, and ciliary neurotrophic growth factor. They play an essential part in the reduction of fibrosis in injured organs.3

Huang et al investigate the usefulness of adipose tissue-derived stem cells  (ADSCs) in a hyperlipidemia-induced overactive bladder models. ADSCs treatment ameliorates functional outcomes and holds promise as a potential new therapy for overactive bladder.4 A systemic review done by Salehi-Pourmehr et al investigates the effect of SC therapy on bladder functional recovery after the onset of spinal cord injury (SCI), multiple sclerosis (MS), PD, and stroke in rodent models. From 1,189 relevant publications, 20 studies met our inclusion criteria of which 15 were conducted on SCI, 2 on PD, 2 on stroke, and 1 on MS in the rodent models. Partial bladder recovery has been evident after SC therapy in SCI models. Due to limitations in the number of studies on other neurological diseases, no conclusions have been drawn.5 In a PD model, cell therapy with human amniotic fluid stem cells and bone marrow-derived mesenchymal stem cells temporarily ameliorated bladder dysfunction.6

Moussa et al conducted the first human study to assess the safety of intradetrusor ADSC injections and their effect on PD-related OAB symptoms. Between January 2019 and December 2020, they performed a prospective trial that enrolled male and female PD patients with symptoms of OAB. A total of 12 patients were randomized into 1 of 2 groups: treatment group (received a single injection into the detrusor muscle of 10ml of ADSC solution), or placebo group (single injection into the detrusor muscle of 10ml of normal saline). The primary outcomes of our study were the change from baseline in OAB symptom score (OABSS) and the overactive bladder questionnaire short form (OAB-q SF) score. Significant improvements from baseline were seen in the OABSS total score in the treatment group compared to placebo at the end of the study (6 months). The mean OABSS total score decreased from 10.33 to 6.83 in the treatment group. In the placebo group, the OABSS remain almost the same between baseline and at 6 months. There were no serious adverse events reported in the treatment or placebo group.7

In conclusion, beyond the great enthusiasm for SCs therapy for OAB in PD patients, heavy investigational work should be done to validate its indication in those patients.

Written by: Mohamad Moussa,1 Mohamad Abou Chakra,2 Athanasios Papatsoris,3 Athanasios Dellis,4 Baraa Dabboucy,5 Michael Peyromaure,6 Nicolas Barry Delongchamps,6 Hugo Bailly,6 Igor Duquesne6

  1. Chairman of Urology Department, Faculty of Medicine, Lebanese University, Beirut, Lebanon.
  2. Department of Urology, Faculty of Medicine, Lebanese University, Beirut, Lebanon.
  3. 2nd Department of Urology, School of Medicine, Sismanoglio Hospital, National and Kapodistrian University of Athens, Athens, Greece
  4. Department of Urology/General Surgery, Areteion Hospital, Athens, Greece.
  5. Department of Neurosurgery, Faculty of Medical Sciences, Lebanese University, Beirut, Lebanon
  6. Department of Urology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, Paris Descartes University, Paris

References:
  1. Moussa M, Abou Chakra M, Papatsoris AG, Dellis A, Dabboucy B, Peyromaure M, et al. Perspectives on the urological care in Parkinson's disease patients. Arch Ital Urol Androl. 2022;94(1):107-117.
  2. Kim JH, Lee SR, Song YS, Lee HJ. Stem cell therapy in bladder dysfunction: where are we? And where do we have to go?. Biomed Res Int. 2013;2013:930713.
  3. Kim JH, Lee HJ, Song YS. Treatment of bladder dysfunction using stem cell or tissue engineering technique. Korean J Urol. 2014;55(4):228-38.
  4. Huang YC, Shindel AW, Ning H, Lin G, Harraz AM, Wang G, et al. Adipose derived stem cells ameliorate hyperlipidemia associated detrusor overactivity in a rat model. J Urol. 2010;183(3):1232-40.
  5. Salehi-Pourmehr H, Hajebrahimi S, Rahbarghazi R, Pashazadeh F, Mahmoudi J, Maasoumi N, et al. Stem Cell Therapy for Neurogenic Bladder Dysfunction in Rodent Models: A Systematic Review. Int Neurourol J. 2020 Sep;24(3):241-257.
  6. Soler R, Füllhase C, Hanson A, Campeau L, Santos C, Andersson KE. Stem cell therapy ameliorates bladder dysfunction in an animal model of Parkinson disease. J Urol. 2012;187(4):1491-7
  7. Moussa M, Abou Chakra M, Dabboucy B, Papatsoris A, Dellis A, Fares Y. Single Intradetrusor Injection Of Autologous Adipose-derived Stem Cells In Parkinson's Disease Patients With Overactive Bladder: A Pilot Study [abstract]. Paper presented at: the International Continence Society (ICS) 2021 Melbourne Online; 14-17 Ocotber. Abstract nr 59.

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Neurogenic Bladder Foundations