Urology, Uro-oncology and Sexology Update

28 UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE The current drugs registered for treating Alzheimer's disease (AD); donepezil, galantamine and rivastigmine provide only a moderate improvement in cognition, activities of daily living, behaviour and overall global function for the treatment of mild and moderate AD. With a rapidly growing elderly population in most developed countries, a breakthrough treatment for AD would be a relief for both patients and clinicians. Surprisingly, that breakthrough treatment might come in the form of sildenal, which is registered for treating erectile dysfunction and pulmonary hypertension. A new Cleveland Clinicled study has identied sildenal as a promising drug candidate to help prevent and treat Alzheimer's disease. The research team utilized a large database of claims data of more than 7 million people living in the U.S which is expected to have over 13.8 million people living with AD by 2050. The research examined the relationship between sildenal and Alzheimer's disease outcomes by comparing sildenal users to non-users. They found that sildenal users were 69% less likely to develop Alzheimer's disease than non-sildenal users after 6 years of follow-up. “Notably, we found that sildenal use reduced the likelihood of Alzheimer's in individuals with coronary artery disease, hypertension and type 2 diabetes, all of which are comorbidities signicantly associated with risk of the disease, as well as in those without,” commented Dr. Cheng. The researchers developed an Alzheimer's patientderived brain cell model using stem cells, in order to try and establish the underlying biological reason for the reduced incidence of AD in sildenal users. In the model, they found that sildenal increased brain cell growth and decreased hyperphosphorylation of tau proteins (a hallmark which leads to neurobrillary tangles). “Because our ndings only establish an association between sildenal use and reduced incidence of Alzheimer's disease, we are now planning a mechanistic trial and a phase II randomized clinical trial to test causality and conrm sildenal's clinical benets for Alzheimer's patients,” said Dr. Cheng. “We also foresee our approach being applied to other neurodegenerative diseases, including Parkinson's disease and amyotrophic lateral sclerosis, to accelerate the drug discovery process.” Interestingly, sildenal citrate was never created for treating erectile dysfunction. It was originally identied as a possible treatment for angina but went on to become the rst oral treatment to be registered for erectile dysfunction when male trial volunteers reported improved erections as one of the side effects. Reference: Fang j, Zhang P, Zhou Y, et al. Endophenotype-based in silico network medicine discovery combined with insurance record data mining identies sildenal as a candidate drug for Alzheimer's disease. Nature Aging, 2021; DOI: 10.1038/s43587-021-00138-z. Will sildenafil be the next breakthrough for treatment Alzheimer's disease?

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