Big data, bench science suggests drugs may slow Parkinson's progress in people

A drug used to treat enlarged prostate may also be able to slow the progression of Parkinson's disease.

The surprising finding, published Sept. 16 online in the Journal of Clinical Investigationis the result of an international collaboration involving researchers in China and at the University of Iowa that combines basic molecular biology with big data.

"Current medicines can partially alleviate some of the symptoms of Parkinson's disease." But this is a change in the history of this neurodegenerative disease. Dr. Michael Welsh, MD, UI Professor of Internal Medicine, Howard Hughes Medical Institute Investigator, and Director of the Pappajohn Biomedical Institute at the UI. "I'm really excited about this finding because I think it has the potential to change the lives of people with Parkinson's disease (and possibly other types of neurodegenerative disease.)"

Lei Liu, Ph.D., Ph.D., at Capital Medical University in Beijing, China, said that terazosin, a prostatic hyperplasia drug, could also block cell death. Liu's team discovered that the cell-protective activity was caused to terazosin's ability to activate an enzyme called PGK1, which is critical for cellular energy production.

That discovery brought Parkinson 's disease (PD) into the picture. Reduced cellular energy production is a hallmark of PD, and energy production declines with aging, which is a primary risk factor for PD. In addition, several inherited forms of PD are caused by genetic defects in cellular energy pathways, and PD in neurons.

The convergence of these lines of research suggests that terazosin's ability to boost energy production in cells might help alleviate cell death in PD. To test the idea, the various experimental models of PD with terazosin. They found that terazosin could prevent neurodegeneration if it was given before the onset of cell death. Moreover, the drug could slow or stop neurodegeneration, even if treatment was delayed until after neurodegeneration had started to develop.

"When we tested the drug in various different models of PD, they all got better," says Liu, a professor at the Beijing Institute for Disease Control. Brain Disorders, who received his doctoral degree in 2002 from the UI working with Welsh.

However, encouraging results in animals do not necessarily predict similar outcomes in people. So, Welsh turned to Nandakumar Narayanan, MD, Ph.D., has a neurologist who cares for patients with PD and studies the disease in people. The search for a patient is more likely to occur in the future than in the past.

Narayanan and Jordan Schultz, PharmD, UI Assistant Professor of Psychiatry, reviewed the Parkinson's Progress Markers Initiative (PPMI) database, which is sponsored by The Michael J. Fox Foundation for Parkinson's Research. The data showed that they were less likely to have a higher risk compared to those of Tamsulosin, for enlarged prostate. Tamsulosin serves as a good control because it is also used to treat benign prostatic hyperplasia, but unlike terazosin, it does not have any effect on the PGK1 enzyme.

The result is promising, but the PPMI is a small database. Only 13 men were identified who were more likely to have PGK1 enzyme, compared to 293 men with PD who were either taking tamsulosin or any of these drugs. While the differences in motor statistics between the two groups were statistically significant, the team looked at the IBM Watson / Truven Health Analytics MarketScan Database, which includes de-identified records of more than 250 million people.

In collaboration with Jacob Simmering, Ph.D., UI Assistant Professor of Internal Medicine, and Philip Polgreen, MD, UI Professor of Internal Medicine and Epidemiology, who had access to the MarketScan Database, the team identified 2880 Parkinson's patients taking one of the group of 15,409 PD patients taking tamsulosin. Using ICD-9 / ICD-10 medical codes to track PD-related diagnoses and hospital or clinic visits for all patients, the data suggests that under real world conditions, terazosin and related drugs reduce the signs, symptoms, and complications of Parkinson's disease .

"What is particularly exciting is that it is a repurposed drug." So, we have a lot of prostate cancer, "Narayanan says. "We are here in the planning phase that we are recruiting patients in Iowa.This is the beginning of what we hope is a sustained and rigorous effort to test this molecule prospectively in order to really determine whether this.

"Narayanan, who is a member of the Pappajohn Biomedical Institute (PBI) and the Iowa Neuroscience," I do not know how to do this. Institute at the UI. "These results grew out of the unique collaborative environment at the University of Iowa and specifically in the PBI, and were really facilitated by our ability and willingness to interact across disciplines."