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AT THE BENCH

Lucy M. Hinder, PhD

On Unearthing a New Cause and Treatment of Peripheral Neuropathy

Talan, Jamie

doi: 10.1097/01.NT.0000472963.03178.a2
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ARTICLE IN BRIEF

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Dr. Lucy M. Hinder, whose research is being presented at this year's American Neurological Association annual meeting, discusses the people and events that influenced her research in diabetic neuropathy.

In late September, Lucy M. Hinder, PhD, a postdoctoral fellow in the University of Michigan's Program for Neurology Research and Discovery, was awarded the 2015 Wolfe Neuropathy Research prize at the American Neurological Association annual meeting. The award is named for a Tennessee businessman, Winston Wolfe, who made his fortune selling safety eyewear and started a foundation to support research on peripheral neuropathy. Dr. Hinder is the first woman and the first scientist without a medical degree to be given this award. In an interview before the meeting, she discussed the events and mentors that helped shape her career.

Lucy Hinder spent her early childhood in transit — moving from the UK to Texas, then from the Netherlands to Scotland, where she remained until 2009. (Her father was in the oil industry, and every promotion at work meant packing up the family to a new home, school, and neighborhood.)

Being on the move made Hinder adaptable and comfortable with meeting and working with a diverse group of friends and colleagues. Always inquisitive, she was interested in science from an early age. No matter where she was, she would speak of that passion to anyone who would listen. She would draw napkin scribbles or use household props (to demonstrate gravity) to draw non-scientists into the fray.

She continued that mission as an undergraduate at the University of Aberdeen, where she majored in biomedical sciences, and spent three summers working for a program called Techfest, which teaches science to children through hands-on workshops. She wanted everyone to be excited about the science she gets to do every day.

It was at the university that she was also inspired to pursue a career in research that would eventually bring her to the US, where her papers and work would earn her this year's Wolfe Neuropathy Research prize.

During her second summer at the university, she began working for a scientist interested in learning, memory, and place preference. Gernot Riedel, PhD, the chair of systems neuroscience, invited the student to join a project studying the effects of cannabinoids on learning and memory.

“I loved the problem-solving aspects of research and figuring out ways to better understand disease and test ideas for potential therapies,” said Dr. Hinder.

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THE FOCUS ON ANIMAL MODELS

Dr. Hinder became increasingly interested in the neurovascular aspects of diabetic neuropathy during her doctoral studies at the University of Aberdeen. There, she found mentors in Mary Cotter, PhD, and Norman E. Cameron, PhD, two diabetes researchers who taught her about physiology and the importance of animal work.

In Dr. Cotter's lab, Dr. Hinder discovered that a direct neurodegenerative process — not just microvascular components — could lead to neuropathy. “Diabetic complications are traditionally thought to be due to hyperglycemia (high blood glucose levels). Our research, both clinically and in the lab, suggests that diabetic neuropathy in type 2 diabetes may be more related to aspects of the metabolic syndrome (obesity, impaired glucose tolerance, dyslipidemia) than to high blood glucose,” the scientist told Neurology Today in describing research she presented at this year's ANA annual meeting.

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IGF-1 IN PERIPHERAL NEUROPATHY

The role of insulin-like growth factor 1 (IGF-1) in peripheral neuropathy had been explored previously, but not in the specific paradigm that Dr. Hinder was using.

The reflex she studied was on the field of skin innervated by those peripheral nerves. Stimulating those nerves resulted in a reflex increase in blood flow to the corresponding area of the skin. Dr. Hinder observed that the reflex increase in skin blood flow was compromised in diabetes, and giving the diabetic rats replacement IGF-1 therapy restored the reflex. Administering therapies to improve the blood supply to the peripheral nerves did not restore the skin reflex.

Dr. Cotter taught her that diabetes is a systemic condition and it takes an understanding of the whole body — every tissue and every organ working together — to come up with answers that can ultimately help patients.

And that is basically what she told colleagues who came to listen to her talk in the fall of 2008 when she presented her research at the Peripheral Nerve Society meeting in Italy.

At the symposium dinner that night, she found herself seated next to Eva Feldman, MD, PhD, FAAN, an endowed professor of neurology at the University of Michigan Health System and director of the Taubman Institute and Program for Research and Discovery. Dr. Feldman was also a coauthor of The Atlas of Neuromuscular Diseases and the editor of a book on IGF-1 that was nighttime reading for Dr. Hinder.

They talked for a good 30 minutes straight, with Dr. Hinder explaining in great detail the research she was doing with animal models of diabetes. At some point in the discussion, Dr. Feldman leaned in toward Dr. Hinder.

“I really enjoyed your talk,” Dr. Feldman told the young scientist. “You have a job in my lab if you want it. Consider this your interview.”

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A RESEARCH HOME IN THE US

Five months later (in 2009), Dr. Hinder packed one suitcase and headed out of Scotland. When she touched down in Michigan, she remembers thinking that if things didn't work out, she could could just head home. That was more than six years ago.

Dr. Hinder's research, in collaboration with Dr. Feldman and many other researchers in their lab, suggests that diabetic neuropathy in type 2 diabetes may be more related to aspects of the metabolic syndrome than to high blood glucose.

Dr. Hinder has been developing new animal models of diabetic neuropathy, working on a high-fat diet-induced model that should improve understanding of complications in type 2 diabetes. This model allows her to focus on a more pre-diabetes phenotype to understand this “metabolic neuropathy,” she said. [For more about her research, see the story, “A New, More Effective Model for Peripheral Nerve Damage Associated with Metabolic Syndrome and Type 2 Diabetes.”]

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These new mouse models will allow her to investigate the contribution of tissue-specific metabolic reprogramming to the development of diabetic neuropathy, she said. Dr. Hinder previously reported that there is a graded decrease in energy metabolites that correlate with the “stocking and glove” presentation of diabetic neuropathy. (The Journal of Endocrinology selected her study as one of the most outstanding papers of 2013.) She is currently investigating dynamic metabolic flux in the peripheral nerve and specific changes in mitochondrial function.

The Feldman lab is also developing treatments that target many of the nerve problems associated with diabetes. “We know that one size does not fit all diabetics,” said Dr. Hinder, who is also amassing experience with some of the latest tools that measure gene expression in the nerve itself. She is currently funded through the Juvenile Diabetes Research Foundation Angelika Bierhaus Postdoctoral Fellowship in Diabetic Complications.

“In Eva's lab, I have been trained to think critically and to function as an independent scientist, while working collaboratively,” Dr. Hinder said. “She has taught me that being a successful scientist isn't about having all the answers, but about asking the right questions and being able to work with people who will help you make discoveries that get you closer to those answers. I have learned to take critical feedback positively and harness that into a better scientific process.

“I love when I have an idea and go into Eva's office to talk,” said Dr. Hinder. “She is always excited and always asks, ‘What's the next step?’”

Six years after that chance conversation over dinner, Dr. Hinder was invited to chair her first session at the Peripheral Nerve Society meeting.

“The most valuable lesson I have learned from Eva is to arrive to work happy and eager to solve new problems,” she said.

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LINK UP FOR MORE INFORMATION:

•. More about Dr. Lucy M. Hinder's research: http://bit.ly/hinder-research
    © 2015 American Academy of Neurology