Patients with neurological disorders such as multiple sclerosis, Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis develop a wide range of lower urinary tract symptoms (LUTS) including urinary urgency, frequency, incontinence, nocturia. Neurogenic bladder dysfunctions observed in patients with neurological disorders usually result from damage to the peripheral and/or central nervous systems. The lack of understanding of pathophysiology and mechanisms underlying LUT dysfunctions in neurological disorders hampers the development of therapeutic strategies and treatment options for these patients. In response to the RFA-DK-12-003, we propose to form the Philadelphia Interdisciplinary Research Center on Neurogenic Bladder Dysfunctions. The primary focus of the Center will be on understanding the systemic and cellular mechanisms of neurogenic bladder dysfunctions resulting from degeneration in the CNS in order to clarify functional interplay between the urologic and nervous systems. The Philadelphia Center will: a) provide the intellectual infrastructure to tackle on projects that will become comprehensive programs determining the underlying etiology of LUTS in neurological disorders;b) establish a well-integrated interdisciplinary research team of clinical and basic science researchers in the Greater Philadelphia area which will focus the research efforts on LUTS using animal models of neurogenic bladder dysfunctions;c) extend the phenotyping of LUTS from animal models to patients diagnosed with neurological disorders and complaining of LUTS, and d) generate preliminary data necessary to submit a program project (POI) after completion of this study. The research team will include established investigators with diverse expertise in neurourology, neurophysiology, pharmacology, microbiology, neurodegeneration, and clinical neurology. The Philadelphia IR-BU Center W consist of: 1) the laboratories of key investigators and their collaborators that combine expertise in neurology, neurourology, neurophysiology, cellular biology, microbiology, neuroscience, pharmacology, and pathology;2) an Administrative Core to provide administrative and fiscal oversight, quality control for the research, coordination of interactions among key investigators in the Center and organization of monthly meetings;3) an Animal tissue core to provide tissues from mice with different levels of neurodegeneration and demyelination for basic research projects;4) an Educational Enrichment Program to attract young investigators to the field of urology and support their research in the laboratories of key investigators.
Patients with neurological disorders such as multiple sclerosis, Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis develop a wide range of LUTS. The Philadelphia IR-BU Center will take an integrative translational approach to study neurogenic bladder dysfunctions resulted from neurological disorders. Understanding of pathophysiology and mechanisms underlying lower urinary tract dysfunctions in neurological disorders will help develop new therapeutic strategies and treatment options for these patients.
|Weissbart, Steven J; Pechersky, Dasha; Malykhina, Anna et al. (2017) The impact of pontine disease on lower urinary tract symptoms in patients with multiple sclerosis. Neurourol Urodyn 36:453-456|
|Weissbart, Steven J; Lewis, Rusell; Smith, Ariana L et al. (2016) Impact of Dry Mouth on Fluid Intake and Overactive Bladder Symptoms in Women taking Fesoterodine. J Urol 195:1517-22|
|McMillan, Matthew T; Pan, Xiao-Qing; Smith, Ariana L et al. (2014) Coronavirus-induced demyelination of neural pathways triggers neurogenic bladder overactivity in a mouse model of multiple sclerosis. Am J Physiol Renal Physiol 307:F612-22|
|Moore, Kate H; Malykhina, Anna P (2014) What is the role of covert infection in detrusor overactivity, and other LUTD? ICI-RS 2013. Neurourol Urodyn 33:606-10|
|Lamarre, Neil S; Braverman, Alan S; Malykhina, Anna P et al. (2014) Alterations in nerve-evoked bladder contractions in a coronavirus-induced mouse model of multiple sclerosis. PLoS One 9:e109314|