Promising research on treating kidney stones, combating Alzheimer's and Parkinson's
January 1, 2022 | View PDF
New handheld technology is ushering a new approach to treating kidney stones
Physicians may be able to maneuver small kidney stones to the ureter so they can be expelled naturally. Patients dealing with small kidney stones that persist after surgery may soon have options to “push” the stones from their body, rather than face another invasive procedure.
A clinical trial at the Kidney Stone Center at the UW Medical Center in Seattle is testing the ability of ultrasound waves to dislodge and move small fragments left behind after surgery so they can naturally be expelled. So far, the results have been good, according to Dr. Mathew Sorensen, a UW Medicine urologist.
“All the surgeries that we do to treat stones have the potential to leave fragments behind,” Dr. Sorensen noted. “Some of those fragments, especially if they’re small, usually clear pretty quickly. But the ones that stay and hang out, especially if they stay in the bottom of the kidney, they have the potential to grow and lead to another event such as surgery or an unpleasant emergency room visit down the road.”
The ultrasound procedure being tested does not require anesthesia, just one or two clinic visits of about 30 minutes each. NASA is particularly interested in this technology. For astronauts on long missions in a weightless environment, kidney stones are a real concern because no surgical option exists to treat the condition in flight.
More than 30 astronauts have reported kidney stones within two years of space flight, so NASA assumes a similar situation could develop during a trip to Mars or the moon. Kidney tissue samples from UW Medicine were recently flown to the International Space Station to observe kidneys’ function in space. Dr. Sorensen’s group also is exploring using ultrasound to break larger stones into small pieces, and then use this handheld device to push and expel the fragments to help resolve a painful event. This may allow treatment of stones without anesthesia and pose an attractive option for at-risk patients, such as those with spinal cord injuries.
Sildenafil may help combat Alzheimer’s disease
A new study by researchers at the Cleveland Clinic is suggesting that sildenafil (Viagra) may be a promising drug candidate to help prevent and treat Alzheimer’s disease. The research team used computational methodology to screen and validate FDA-approved drugs as potential therapies for Alzheimer’s disease. Through a large-scale analysis of a database of more than 7 million patients, they determined that sildenafil is associated with 69% reduced incidence of Alzheimer’s disease, indicating the need for follow-up clinical trial testing of the drug’s efficacy in patients with the disease.
Without the development of effective new treatments, Alzheimer’s disease is set to impact 13.8 million Americans by 2050, underscoring the need for rapid development of prevention and treatment strategies. Drug repurposing (use of an existing drug for new therapeutic purposes) offers a practical alternative to the costly and time-consuming traditional drug discovery process.
“This paper is an example of a growing area of research in precision medicine where big data is key to connecting the dots between existing drugs and a complex disease like Alzheimer’s,” said Dr. Jean Yuan, program director of Translational Bioinformatics and Drug Development at the National Institute on Aging (NIA) in Bethesda, Maryland, part of the National Institutes of Health (NIH), which funded this research. “This is one of many efforts we are supporting to find existing drugs or available safe compounds for other conditions that would be good candidates for Alzheimer’s disease clinical trials.”
The research team has found that understanding subtypes of neurodegenerative diseases such as Alzheimer’s disease may help to reveal common underlying mechanisms and lead to the discovery of actionable targets for drug repurposing.
The buildup of beta amyloid and tau proteins in the brain leads to amyloid plaques and tau neurofibrillary tangles are hallmarks of Alzheimer’s-related brain changes. However, no FDA-approved, anti-amyloid or anti-tau small molecule Alzheimer’s treatments currently exist. Tragically, the clinical trials for such treatments have failed in the past decade. Recent studies show that the interplay between amyloid and tau is a greater contributor to Alzheimer’s than either by itself, according to the researchers.
Using a large gene-mapping network, researchers integrated genetic and other biologic data to determine which of over 1,600 FDA-approved drugs could be an effective treatment for Alzheimer’s disease. They pinpointed drugs that target both amyloid and tau as having higher scores compared to drugs that target just one or the other. The current study showed sildenafil, which has been shown to significantly improve cognition and memory in preclinical models, according to the investigators.
Combating Parkinson’s disease in a new way
A new agent is showing promise for minimizing erratic movements in Parkinson’s patients. A study from Texas Biomedical Research Institute (Texas Biomed) and collaborators has identified a promising drug candidate to minimize uncontrolled, erratic muscle movements (dyskinesia) associated with Parkinson’s disease.
The small molecule, called PD13R, reduced dyskinesia by more than 85% in an animal model of Parkinson’s disease. The animals experienced much better sleep taking this compound compared to another drug often prescribed for dyskinesia. The results, which were published in the journal Experimental Neurology, showed this agent could be highly valuable to individuals with Parkinson’s disease.
Dyskinesia is a common side effect in patients with Parkinson’s disease. It is not a symptom of the disease itself, but typically emerges about five years into taking levodopa, the leading medication used to restore balance, reduce shaking, and manage other motor control issues patients experience.
“Levodopa is amazing. It works like magic, but it has side effects. If we can eliminate these side effects, it could change the life of patients with Parkinson’s,” said lead study author Marcel Daadi, an associate professor at Texas Biomed in San Antonio, Texas.
Designing drugs for Parkinson’s and its side effects is notoriously difficult. This is in part due to the progressive nature of the disease as neurons deteriorate, and because it involves the neurotransmitter dopamine. There are five types of dopamine receptors, all with different functions, yet very similar structures. Finding a compound that only interacts with the desired receptor is a major challenge.
John Schieszer is an award-winning national journalist and radio and podcast broadcaster of The Medical Minute. He can be reached at email@example.com.