Bev Anderson knew something was wrong.

“All my life I've known my feet didn't have the strength and capability of most of the people I knew,” she recalled.

In high school, she began experiencing severe pain. Her family physician   diagnosed her as having “growing pains.”

They weren't.

It wasn't until after she'd retired from her 34-year career as an elementary school teacher in Concord that a neurologist correctly diagnosed her—and her brother--as having peripheral neuropathy, a disease that afflicts more than 30 million people in the United States alone. Specifically, she and her brother inherited Hereditary Sensory Autonomic Neuropathy or HSAN.

Anderson's journey to learn more about peripheral neuropathy and to help others led her to co-found the Western Neuropathy Association (WNA) in Auburn in 1998, and serve as its president for the last two decades.

Her 20-year journey of hope recently led to the University of California, Davis, where distinguished professor Bruce Hammock is researching an enzyme aimed at controlling acute and neuropathic pain.

Anderson and WNA treasurer Darrell O'Sullivan, a former lab manager at the UC Davis Medical Center, recently visited the Hammock lab to present a $5000 check from the association to EicOsis, the Davis company that Hammock founded to move inhibitors of the soluble epoxide hydrolase into human clinical trials.

“We raised the money through $2,500 from our budget, and from voluntary donations from members and friends,” she said. “One member donated $1000 and asked it to be matched.”

“It was heartwarming to receive a $5000 check from this dedicated, grass-roots group,” said Hammock, whose research on the compounds spans nearly 50 years. “We are touched.”

 

Anderson and O'Sullivan toured Hammock's lab in Briggs Hall, UC Davis Department of Entomology and Nematology, and discussed his research and the WNA mission and goals.

“There are medications that help the symptoms, but no cure yet,” Anderson said, adding that the Hammock discovery “may be close to a cure for some people who have pain and inflammation.”

 "On behalf of EicOsis I want to thank the Western Neuropathy Association, and particularly Bev Anderson and Darryl O'Sullivan, for championing this effort," Hammock said. "Everyone at EicOsis is touched by the confidence they have put in us to develop a treatment for chronic pain.  There are never guarantees in drug development, but certainly their support drives us to work hard to move this drug through FDA and on to clinical trials."

"We are, of course, working to raise support from federal agencies, venture funds and the pharmaceutical industry, but this support from Bev and her associates is heartfelt and inspiring.  It illustrates what a great need there is to develop treatments for pain," Hammock said.  "The fact that the support is coming from so many of the people who are suffering from pain is particularly inspiring."

"It is inspiring about how upbeat the individuals are in these organizations as they support each other and exchange approaches in dealing with pain," he pointed out. "But underlying these optimistic conversations is the reality that pain can be an overpowering factor compromising the leading a full and health life.  We must find a solution to the problems of pain and neuropathy."

The clinical trials, expected to begin next year, will target chronic or neuropathic pain with a non-opiate analgesic.  In parallel, Hammock and his UC Davis colleagues are developing a drug to treat a commonly fatal pain condition in horses called laminitis as well as arthritic pain in dogs and cats. 

Hammock traces the history of his work to 1969 to his graduate student days in the laboratory of UC Berkeley Professor John Casida.  Hammock was researching insect developmental biology and green insecticides when he and colleague Sarjeet Gill, now a distinguished professor at UC Riverside, discovered the target enzyme in mammals that regulates epoxy fatty acids.

“The work led to the discovery that many regulatory molecules are controlled as much by degradation and biosynthesis,” Hammock said. “The epoxy fatty acids control blood pressure, fibrosis, immunity, tissue growth, pain and inflammation to name a few processes.”

Peripheral neuropathy is a complex disease. It refers to “the many conditions that involve damage to the peripheral nervous system, the vast communication network that sends signals between the central nervous system (the brain and spinal cord) and all other parts of the body,” according to the National Institute of Neurological Disorders and Stroke. “Best known are the signals to the muscles that tell them to contract, which is how we move, but there are different types of signals that help control everything from our heart and blood vessels, digestion, urination, sexual function, to our bones and immune system. The peripheral nerves are like the cables that connect the different parts of a computer or connect the Internet. When they malfunction, complex functions can grind to a halt.”

“There are over 150, some say over 200, known causes of neuropathy,” said Anderson, a resident of Colfax.  “Diabetes is considered a chief cause. but chemotherapy and likely hereditary neuropathies are gaining on it.”

Although the peripheral neuropathy she has is HSAN, “there are10 or more hereditary types,” she said. “HSAN is unique in its early onset as I could have been diagnosed by kindergarten if medical science had been up to it then.” The neurologist who correctly diagnosed her told her she had “The neuropathy walk.” 

“One aspect is that toes naturally go outward for better balance,” Anderson explained. “I call them my ‘outrigger toes.'  With neuropathy, it usually starts with tingling like the foot is asleep and waking up and progresses into numbness.  Pain of various types and intensities may follow.  It boggles the mind to have feet so numb that surgery could be done on them without anesthesia but they still have pain.  It depends on the amount of nerve damage.”

“There is a long list of other symptoms:  sensory ones like feelings of hot or cold when the feet or hands are not hot or cold to the touch, deep itching, feeling like you are wearing a stocking or glove when you aren't, etc., motor ones like balance, and movement concerns, and autonomic ones that are internal as all internal organs are operated by peripheral nervous system.  Blood pressure, kidney function, urinary tract, digestive system, sexual feelings, etc. are affected by the health of the nerves.”

Anderson noted that neuropathy “usually starts in the longest nerve which is the one that goes to the toes.  When the progress gets up to the knees, it may start in the fingers and hands as that is now about the same length.  However, it may also start in the hands if the injury that causes the neuropathy is in the cervical spine area initially. “

The mission of WNA, comprised of 500 members and many other attendees in California, Oregon and Nevada, is “to provide support, information and referral to people with neuropathy and to those who care about them, to inform and connect with the health care community and to support research,” Anderson said. The all-volunteer organization seeks to establish and develop support groups in as many cities as possible.

Highly honored for his work, Hammock is a member of the National Academy of Sciences and the National Academy of Inventors. He received an outstanding achievement award from the international Eicosanoid Research Foundation at its 2017 meeting in Puerto Vallarta, Mexico, where he delivered a plenary lecture on “Control of Acute and Neuropathic Pain by Inhibiting the Hydrolysis of Epoxy Fatty Acid Chemical Mediators: Path to the Clinic.”

Hammock's career took him from UC Berkeley to the U.S. Army Academy of Health Science in San Antonio, Texas; to a Rockefeller Foundation Fellowship at Northwestern University, Evanston, Ill., and to UC Riverside, where he served as an assistant and associate professor before he joined the UC Davis faculty in 1980. He holds a joint appointment with the UC Davis Department of Entomology and Nematology and the UC Davis Comprehensive Center for Cancer Research.

Hammock collaborates with scientists worldwide in unprecedented research with a multidisciplinary, integrated approach to research focused on insect biology, mammalian enzymology, and analytical chemistry. He has authored more than 1000 publications on a wide range of topics in entomology, biochemistry, analytical and environmental chemistry in high quality journals. In the epoxide hydrolase field, the Hammock laboratory has published almost 900 peer-reviewed papers.

“For many years Sarjeet and I were alone in studying this enzyme and pathway but now its importance is well recognized in mammalian biology with over 17,000 peer reviewed papers in the area,” Hammock said. “The importance of this pathway is now clear.”

The Hammock laboratory is the home of the UC Davis/National Institute of Environmental Health Sciences Superfund Program.   The laboratory has generated more than 80 patents, 300 postdoctoral fellows, and more than 65 graduates, who now hold positions of distinction in academia, industry and government.

“It is always important to realize that the most significant translational science we do in the university is fundamental science,” said Hammock. “The extreme and poorly treated pain that I observed as a medical officer in a burn clinic in the Army, is a major driver for me to translate this knowledge to help patients with severe pain.  Hopefully, we can start human clinical trials next year.” 

Bev Anderson and fellow members of WNA hope so, too. It's been a long journey, from misdiagnosis to rays of hope to bursts of optimism.