- Author: Kathy Keatley Garvey
The paper, which indicates that a brain enzyme could play a key role in curbing or preventing the progression of Parkinson's disease, is one of four singled out as exemplary on the NIEHS website.
“This could be a “revolutionary paper that could cure Parkinson's disease,” commented co-author Bruce Hammock, a UC Davis distinguished professor of entomology with a joint appointment with the UC Davis Comprehensive Cancer Center. He is the 30-year director of the UC Davis NIEHS Superfund Program, which helped fund the research. "A related compound to the drug used in the paper will enter human safety trials sponsored by NIH in early 2019."
The team of 14 scientists demonstrated that inhibiting the enzyme soluble epoxide hydrolase (sEH) compound in mice helped curb the inflammation associated with the development and progression of Parkinson's disease (PD), an age-related brain disorder that affects a million Americans, mostly 60 and over.
The researchers exposed mice to methyl-4-phenyl-1, 2, 3, 6 tetrahydropyridine (MPTP), a neurotoxicant that leads to symptoms of PD in animals. They found two approaches that protected against MPTP-induced neurotoxicity in the mouse brain--adding a potent sEH inhibitor, and genetically modifying mice to not produce sEH.
“Our research suggests that the sEH inhibitor may prevent the progression of Parkinson's disease (PD) as well as treat patients with dementia of Lewy bodies (DLB) if the sEH inhibitor is used in early phases of patients with these disorders,” said Hashimoto, whose career spans 30 years in the development of blood biomarkers and novel therapeutic drugs and includes more than 550 publications on the topic. “Both PD and DLB are chronic and progressive movement disorders. However, the precise causes of these diseases are largely unknown.” Lead author was Qian Ren of the Hashimoto lab.
Hammock and a colleague Sarjeet Gill (now of UC Riverside) discovered the sEH enzyme in a UC Berkeley lab while they were researching insect developmental biology and green insecticides. The work, begun in 1969, led to the discovery that many regulatory molecules are controlled as much by degradation as by biosynthesis, Hammock said. These epoxy fatty acid chemical mediators control blood pressure, fibrosis, immunity, tissue growth, and pain and inflammation.
The Hammock laboratory has published nearly 900 peer-reviewed papers on the sEH enzyme. To date, journals have published more than 17,000 peer-reviewed papers on the sEH enzyme and its inhibitors. Hammock credits the NIEHS with supporting his research in this area since the 1970s.
A Davis-based company, EicOsis, is developing inhibitors to sEH to treat unmet medical needs in humans and animals. The company recently received a multi-million dollar grant from the NIH/NINDS Blueprint Program to move sEH inhibitors through phase I human clinical trials. "We are developing a non-opiate analgesic to treat the chronic pain often associated with diabetes,” said William Schmidt, vice president of clinical development at EicOsis. “Once we have investigational new drug status from the Food and Drug Administration and have finished our phase I trial, physicians will be able initiate their own trials with the EicOsis compound on Parkinson's disease and other Lewy body disorders.”
Hammock said the soluble epoxide hydrolase inhibitors that inhibit the soluble epoxide hydrolase will soon enter human clinical trials supported by the NIH-NINDS Blueprint Program (NIH's Health's National Institute of Neurological Disorders and Stroke). “These drugs could provide relief for patients with a wide variety of inflammatory diseases,” said Hammock, who is a member of the National Academy of Sciences and the National Academy of Inventors.
- Author: Kathy Keatley Garvey
The ground-breaking study, published in the Proceedings of the National Academy of Sciences, was led by NIEHS-funded scientists Robert Tukey, director of the Superfund Research Program at UC San Diego and Bruce Hammock, director of the UC Davis Superfund Research Program.
In its January newsletter, NIEHS ranked the triclosan study No. 2 in grant-funded research published in 2015. Some 2514 NIEHS-funded research papers were published in 2015. The institute, part of the National Institutes of Health, also singled out 27 other papers for special recognition.
Triclosan is a widely used antibacterial chemical found in cosmetics, soaps, shampoos, toothpastes and many other household products, said Hammock, who holds a joint appointment with the UC Davis Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Center. “This study, using laboratory mice, raises concerns about the safety of triclosan in humans,” he said. These findings add to earlier reports triclosan can disrupt hormones and impair muscle contraction.
The paper, “The Commonly Used Antimicrobial Additive Triclosan is a Liver Tumor Promoter,” drew widespread attention from news media, scientists and consumers.
The team also chemically induced liver tumors in the mice and found that the mice exposed to triclosan showed a large increase in tumor multiplicity, size, and incidence compared to unexposed mice.
Hammock said the findings suggest that triclosan's negative effects on the liver may result from interference with the constitutive androstane receptor, which plays a role in clearing foreign chemicals from the body.
Other co-authors of the paper are Mei-Fei Yueh, Koji Taniguchi, Shujuan Chen, R. M. Evans and Michael Karin, all of UC San Diego; and Ronald M. Evans, Salk Institute for Biological Studies.
Hammock was featured in the January 2015 edition of Chemical Research in Toxicology, and in the Sept. 4, 2014 edition of Newsweek in a piece titled "Is Cancer Lurking in Your Toothpaste? (And Your Soap? And Your Lipstick? Hammock called triclosan “quite a good antimicrobial” that belongs in the hospital, not on the kitchen counter, and told reporter Alexander Nazaryan, “There's no reason for it to be there" (in hand and dish soaps).
The research was funded, in part, by U.S. Public Health Service grants ES010337, GM086713, GM100481, A1043477, ES002710 and ES004699.