In a recent study from Johns Hopkins Medicine, scientists found that a drug first developed to treat Alzheimer’s disease, schizophrenia and sickle cell disease could reduce obesity and fatty liver and improve heart function—without changes in food intake or daily activity.
Currently, there isn’t a pill that has been proven effective for treating severe obesity, yet such obesity is a global health problem that increases the risk of many other diseases.
This study follows work reported by the same team in 2015 that first showed the PDE9 enzyme is present in the heart and contributes to heart disease triggered by high blood pressure.
PDE9 is the enzyme cousin of another protein called PDE5, which also controls cyclic GMP and is blocked by drugs such as Viagra. Inhibitors of PDE9 are experimental, so there is no drug name yet.
In the study, researchers examined if PDE9 inhibition may improve common conditions including high blood pressure; high blood sugar, cholesterol and triglycerides; and excess body fat, particularly around the waist.
While PDE9 inhibitors remain experimental, they have been developed by several companies and tested in humans for diseases such as Alzheimer’s and sickle cell.
The current mouse study used a PDE9 inhibitor made by Pfizer Inc. (PF-04447943) that was first tested for Alzheimer’s disease, though eventually abandoned for this use.
Between the two reported clinical trials, over 100 people received this drug, and it was found to be well tolerated with no serious adverse side effects. A different PDE9 inhibitor is now being tested for human heart failure.
According to the U.S. Centers for Disease Control and Prevention, more than 40% of people living in the U.S. are obese; and 43% of American women over the age of 60—long past menopause—are considered obese.
If the findings in mice apply to people, someone weighing 250 pounds could lose about 50 pounds with an oral PDE9 inhibitor without changing eating or exercise habits.
If you care about dementia, please read studies about Vitamin B9 deficiency linked to higher dementia risk, and flavonoid-rich foods could help prevent dementia.
For more information about brain health, please see recent studies that cranberries could help boost memory, and these antioxidants could help reduce dementia risk.
The research was published in the Journal of Clinical Investigation and conducted by David Kass et al.
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