- 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 grant, “Development of an Oral Analgesic for Neuropathic Pain," is funded by the Blueprint for Neuroscience Research. National Institutes of Health (NIH).
The clinical trials, scheduled to begin in 2017, will target diabetic neuropathic pain, occurring in an estimated half of the world's 347 million diabetics, and 29 million Americans.
The compound “is an inhibitor of the soluble epoxide hydrolase (sEH) enzyme,” said Hammock, whose fundamental research on the developmental biology of insects led to the discovery. “It is a key regulatory enzyme involved in the metabolism of fatty acids and treats pain by stabilizing natural analgesic and anti-inflammatory mediators.”
“We are really honored to have been the first company to enter directly into the clinical development phase of the NIH Blueprint Neurotherapeutics Network award program,” said William Schmidt, EicOsis vice president of clinical development. “Since this was a highly competitive grant, this demonstrates the enthusiasm that the NIH has for developing non-opioid therapeutic options for treating severe pain. With the support and direct collaboration of outside experts in the NIH network, we look forward to advancing this novel type of analgesic drug into human clinical trials.”
Current therapies for diabetic neuropathy pain are ineffective in more than three of four patients. “The EicOsis technology may solve a great need in pain treatment in providing a powerful analgesic which avoids the side effects of opioids (narcotics) and nonsteroidal anti-inflammatory drugs (NSAIDs),” said physician Scott Fishman, professor and chief of the Division of Pain Medicine, UC Davis Health System, who is not affiliated with the company. “The EicOsis compound holds great promise for controlling neuropathic pain in general and particularly for this difficult and common medical problem.”
Hammock said EC5026 and close analogs have already shown to be effective “against naturally-occurring moderate-to-severe pain in dogs, cats, and horses.”
The $4 million grant will provide both financial support and shared resources for advancing the EicOsis compound through early clinical trials. The Blueprint for Neuroscience Research is a cooperative effort among the 15 NIH Institutes, centers and offices that support neuroscience research and accelerates discoveries through pooled resources and expertise.
"The Blueprint has funded early drug development efforts in the past, but EicOsis is the first group in the nation to be funded in their advanced development phase," said EicOsis project manager Cindy McReynolds, program manager of the Hammock lab in the UC Davis Department of Entomology and Nematology.
EicOsis (pronounced eye-cosis), is described on its website, http://www.eicosis.com/, as a privately held Davis-based company developing a first-in-class therapy of a once daily, oral treatment for neuropathic and inflammatory pain in humans and companion animals. Hammock developed the technology for the lead compound. UC Davis licensed the compound exclusively to EicOsis. The company maintains a strong patent position with both method-of-use and composition-of-matter patents.
Research was supported by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under Award Number UH2NS094258.
Much of the research was supported through the UC Davis Department of Entomology by the NIH, National Institute of Environmental Health Sciences (NIEHS), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the American Asthma Society.
Hammock is a fellow of the National Academy of Inventors, which honors academic invention and encourages translations of inventions to benefit society. He is a member of the U.S. National Academy of Sciences, a fellow of the Entomological Society of America, and the recipient of the Bernard B. Brodie Award in Drug Metabolism, sponsored by the America Society for Pharmacology and Experimental Therapeutics. He directs the campuswide Superfund Research Program, National Institutes of Health Biotechnology Training Program, and the National Institute of Environmental Health Sciences (NIEHS) Combined Analytical Laboratory.
A member of the UC Davis faculty since 1980, Hammock received his bachelor of science degree magna cum laude from Louisiana State University in entomology and chemistry, and his doctorate from UC Berkeley in entomology and toxicology, working in xenobiotic metabolism. (For biographies on the other EicOsis officers, see website on EicOsis personnel.)
For more information, access the website at http://www.eicosis.com or contact project managere Cindy McReynolds at firstname.lastname@example.org or 530-341-4194.
Key mechanism that causes neuropathic pain found (July 7, 2015)
A biological process called endoplasmic reticulum stress appears to play a key role in causing neuropathic pain, according to a new study. The discovery could eventually lead to new therapeutics for controlling chronic pain associated with trauma, diabetes, shingles, multiple sclerosis or other conditions that cause nerve damage.
UC Davis to test experimental drug for laminitis in horses (VIDEO) (Nov. 14, 2012)
Veterinarians at the UC Davis School of Veterinary Medicine have announced plans to conduct the first clinical trial of an experimental drug that has shown promise in treating horses stricken with laminitis, an excruciatingly painful and often life-threatening foot-related disease.
Discovery could help combat chronic pain in diabetics (June 26, 2015)
Researchers at UC Davis have discovered a class of natural compounds found within the body that may someday lead to pain relief for millions of diabetics and others suffering from chronic pain.
Pest Control Research Leads To Pain Control Discovery (Sept. 1, 2006)
A newly discovered enzyme inhibitor, identified by researchers originally looking for biological pest controls, may lead to pain relief for sufferers of arthritis and other inflammatory diseases, say UC Davis researchers. The finding, hailed by a noted inflammatory disease expert "as the most important discovery in inflammation in more than a decade," may also reduce side effects associated with the painkiller, Vioxx.