PNR&D Director earns Laureate Award from Endocrine Society

Washington, DC— Eva L. Feldman, MD, PhD, the Director of the Program for Neurology Research and Discovery, has earned the Endocrine Society’s prestigious 2017 Laureate Award.

Dr. Feldman, the University of Michigan’s Russell N. DeJong Professor of Neurology and Director of the A. Alfred Taubman Medical Research Institute, is the winner of the Gerald D. Aurbach Award for Outstanding Translational Research. This annual award recognizes outstanding contributions to research that accelerate the transition of scientific discoveries into clinical applications. She is a clinician-scientist whose basic and clinical research has led to new disease therapies, changed clinical guidelines, and made her an opinion leader in neurology.

She conducted pioneering studies on the causes of nerve damage in metabolic diseases and later used cell-based and novel mouse models as well as human transcriptomics to discover pathways that are disrupted in diabetic neuropathy. She developed a clinical tool for diagnosing diabetic neuropathy that is used worldwide and in multiple clinical trials. An author of more than 350 publications, she is a past President of the American Neurological Association, has received numerous awards, and is a member of the National Academy of Medicine.

Endocrinologists are PhDs and MDs who specialize in untangling complex symptoms to study, diagnose, treat, research or cure hormone-related conditions. These professionals are responsible for research breakthroughs that lead to the cures of tomorrow and for providing the gold standard of care for patients with hundreds of conditions and diseases such as diabetes, thyroid disorders, obesity, hormone-related cancers, growth problems, reproduction, infertility and rare diseases, among others.

Established in 1944, the Society’s Laureate Awards recognize the highest achievements in the endocrinology field, including groundbreaking research and innovations in clinical care. The Endocrine Society will present the awards to the 14 winners at ENDO 2017, the Society’s 99th Annual Meeting & Expo in Orlando, FL, from April 1-4, 2017.


Buddy’s Pizza president makes $500,000 matching gift for Alzheimer’s research

Robert Jacobs is no stranger to neurological disease: He lost his father to Alzheimer’s disease, and was himself diagnosed with Guillain-Barré syndrome a decade ago.

So the Buddy’s Pizza president takes neurological research personally, and has demonstrated his commitment with a remarkable gift to the Program for Neurology Research & Discovery (PNR&D): He will match up to $500,000 to support research into environmental toxins and their potential link to Alzheimer’s disease.

“Sometimes people make a gift because of family issues or other people’s issues, but I have my own issues,” he said. “My father had Alzheimer’s disease and I’ve had my own syndrome. I believe in Eva (Feldman) and the University of Michigan. It’s pretty simple. It’s actually to make a difference.”

Earlier this year, PNR&D Director Eva L. Feldman, MD, PhD, along with Stephen A. Goutman, MD, and others, published a study that showed a high percentage of patients with amyotrophic lateral sclerosis (ALS) had been exposed to agricultural pesticides. The Jacobs gift gives the PNR&D a jump start on a similar study of Alzheimer’s patients.

“This incredibly generous gift from Bob gives us a chance to make genuine headway in understanding environmental causes behind the growing incidence of Alzheimer’s disease in our aging population,” Feldman said. “By making it a matching gift, Bob has in effect doubled down on this research. We’re excited at the opportunity.”

Jacobs was diagnosed a decade ago with Guillain-Barré syndrome, a disorder that causes the immune system to attack nerves, causing muscle weakness, tingling and paralysis. And while the syndrome wasn’t necessarily a result of toxins Jacobs has long held an interest in environmental toxins and their impacts on human health.

“This gives the team more money to do something with,” he said. “Hopefully this gift will allow them to draw the correlation between toxicity and Alzheimer’s disease. Then the question becomes what you do with that information. With the extra money you can do so much more.”

The need for intensified Alzheimer’s disease research has never been greater. The disease affects 5.2 million people in the United States, a number that is expected to double by 2050. The national cost of caring for the AD population is estimated at over $200 billion annually, according to the Alzheimer’s Association and the National Institute on Aging. Alzheimer’s disease is characterized by an accumulation of abnormal proteins in the brain which, over time, injure and kill brain nerve cells.  As the nerve cells are lost, so is a person’s ability to think, reason and function normally.

About Buddy’s Pizza: Buddy’s Pizza – Detroit’s Original Sicilian Style Square Pizza – was introduced at Buddy’s Rendezvous, a bar in Detroit, in 1946. The business was purchased by Jacobs’ parents, Billy and Shirley Jacobs, in 1970. Today, Buddy’s has 11 locations throughout Metro Detroit.


Pesticide exposure may be risk factor for ALS

New research led by Program for Neurology Research & Discovery Director  Dr. Eva Feldman and other University of Michigan researchers shows environmental pollutants could affect the chances a person will develop amyotrophic lateral sclerosis, or ALS.

There is no cure for this rapidly progressive motor neuron disease, also known as Lou Gehrig’s disease. Those afflicted eventually lose their strength and ability to move their arms, legs and body.

As part of a larger study on environmental risk factors for ALS, U-M scientists published their work on pesticide and other environmental exposures in JAMA Neurology.

“From the first ALS patient I saw over 25 years ago to the ALS patient I diagnosed this week, I am always asked the same question, ‘Why me? What is different about my life that I got this disease?’” says Feldman, co-senior author of the study and a longtime ALS clinician and researcher. “I want to answer that question for my patients.”

Feldman’s team studied 156 people with ALS and 128 people without it. All described their exposure to pollutants at work and at home, with a focus on occupational exposure. The researchers also measured toxic persistent environmental pollutants in blood to gain a more comprehensive assessment of environmental exposures.

“We found these toxic chemicals in individuals both with and without ALS,” says co-first author Stephen Goutman, M.D., director of the U-M Comprehensive ALS Clinic. “We are likely all exposed without our own knowledge, from the air, water and our diet, as these chemicals can last decades in the environment. However, persons with ALS, overall, had higher concentrations of these chemicals, especially in regards to pesticides.”

There was no strong correlation, however, between any particular occupation and likelihood of developing ALS, except for service in the armed forces, a link found in previous studies.

Blood tests showed increased odds of ALS for those with exposure to several different types of chemicals, many of which are no longer widely used because of environmental concerns, such as the infamous pesticide DDT. Some of the classes of chemicals studied, however, such as polybrominated diphenyl ethers, used as flame retardants, have only experienced recent scrutiny as potential health hazards.

“The challenge is that persons are likely exposed to multiple chemicals and therefore it is too soon for us to know whether individual chemicals, or mixtures of chemicals, lead to motor neuron damage,” Goutman says. “Next, we will really dive into particular chemicals that could be risk factors for the disease.”

‘The first and very important step’

The researchers believe a better understanding of environmental risk factors for ALS could lead to an understanding of why persons develop ALS and also help to explain clusters of ALS cases in different geographical areas.

“This is the first and very important step to identifying what specific exposures are associated with ALS — to answering the ‘why me?’ question,” Feldman says. “Now it is time to understand how these exposures lead to disease with an eye to halting ALS onset. As one of my patients said to me before he died, we want a ‘world without ALS.’”

The Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry, the National Center for Research Resources and the National Center for Advancing Translational Sciences provided support for this research.

PNR&D director among Michigan’s “Influential Women”


Eva Feldman, M.D., Ph.D., Director of the Program for Neurology Research & Discovery, is among the 100 most influential women in Michigan, according to a Crain’s Detroit Business special report.

The honorees include leaders in business, academia, nonprofits and public policy from across the state.

Feldman, a neurologist and leading ALS researcher, is the Russell N. DeJong Professor of Neurology, as well as Director of the A. Alfred Taubman Medical Research Institute at the University of Michigan. Crain’s touts her research team’s oversight of Phase 2 U.S. Food and Drug Administration trials treating ALS patients with injections of embryonic human stem cells.

Another distinguished U-M executive, Marianne Udow-Phillips, MHSA,also was named by Crain’s.  Udow-Phillips directs U-M’s Center for Healthcare Research & Transformation (CHRT). Crain’s highlights Udow-Phillips’ role in working with the state of Michigan and writing the winning grant for the 5-year, $110 million Michigan Primary Care Transformation demonstration project (MiPCT).

To read the full profiles of both women, or to view the full list of honorees, visit

Eva Feldman, MD, PhD, receives Physician of the Year Award

New York — University of Michigan physician and researcher Eva L. Feldman, MD, PhD, will be honored as one of America’s top doctors at the 11th Annual National Physician of the Year Awards, to be held March 21, 2016, in New York.


Eva L. Feldman, MD, PhD

Presented by Castle Connolly Medical Ltd., the awards annually recognize and honor exemplary physicians practicing in communities throughout the United States.

Dr. Feldman is one of three recipients of the Clinical Excellence Award.

“It is such an honor to be recognized, but this is truly the result of tremendous teamwork,” said Dr. Feldman, the Russell N. DeJong Professor of Neurology, who in addition toe her clinical work also serves as Director of the A. Alfred Taubman Medical Research Institute and as Director of the Program for Neurology Research and Discovery. “The University of Michigan attracts such talented and dedicated people to serve our patients in every way, through brilliant staff, cutting-edge research and world-class facilities. I feel deeply privileged to be a practicing clinician-scientist at the University of Michigan.”

In addition to her clinical work she also serves as Director of the A. Alfred Taubman Medical Research Institute and as Director of the Program for Neurology Research and Discovery.

Dr. Feldman is on the forefront of applying stem cell research to human disease. She is the Principal Investigator of the first clinical trial of intraspinal transplantation of stem cells in patients with ALS, which completed Phase 2 in 2014. To date, 30 patients have received up to 16 million stem cells injected directly to their spinal cords and a similar therapy is being studied for use in patients with Alzheimer’s disease.

She has published more than 325 original peer-reviewed articles, 60 book chapters and three books. Dr. Feldman has more than 25 years of continuous NIH funding and is currently the Principal or Co-Investigator of five major National Institutes of Health research grants, three private foundation grants and one clinical trial focused on understanding and treating neurological disorders, with an emphasis on ALS and diabetic neuropathy.

Her many honors including the Early Distinguished Career Award and the Distinguished Faculty Achievement Award from the University of Michigan, along with several scientific achievement awards in the field of diabetes. In 2010 she was elected to the Johns Hopkins Society of Scholars, and she has been listed in Best Doctors in America for more than 12 consecutive years. She served as President of the American Neurological Association from 2011 to 2013, was elected to the National Academy of Medicine in 2014.

Dr. Feldman to speak at Lawrence Tech March 29

PNR&D Director Eva Feldman, M.D., Ph.D., has been invited to present her research at 7:30 p.m. on Tuesday, March 29 at Lawrence Technological University in Southfield. The event is part of Lawrence Tech’s Walker L. Cisler Memorial Lecture Series.

Dr. Feldman lecture is titled “Stem Cells in the Treatment of ALS: A New Way Forward,” and will be presented in the Mary E. Marburger Science and Engineering Auditorium (S100) Science Building, Lawrence Technological University. Lawrence Tech is located at 21000 West 10 Mile Road in Southfield.

Dr. Feldman’s lecture will focus on the status of her ground-breaking clinical trial, in which more than 30 ALS patients received injections of stem cells in their spinal cords. Phases 1 and 2 of the trial showed that the procedure is safe and well-tolerated by patients, and 70 percent of those who received the stem cells recovered to levels higher than historic controls. A third phase of the trial is currently being designed.

PNR&D team publishes key Alzheimer’s findings

Scientists in the Program for Neurology Research & Discovery drew one step closer to understanding the benefits stem cells provide in the fight against Alzheimer’s disease, with publication last month of an article in the scientific journal Stem Cells Translational Medicine.

The article was one of five published by PNR&D scientists in January alone.

The Alzheimer’s article, “Human Cortical Neural Stem Cells Expressing Insulin-Like Growth Factor-I: A Novel Cellular Therapy for Alzheimer’s Disease,” e-published January 7, 2016, demonstrated in cell culture models that stem cells expressing a neuroprotective growth factor promote the development of new cells and synapses, enrich the environment for neurons to thrive, and offer improved protection against Alzheimer’s disease insults. The paper also demonstrates that the cells can survive in the brain of a mouse model of Alzheimer’s disease following transplantation, supporting continued testing for effects on learning and memory. The stem-cell line used in the experiment was developed by PNR&D scientists in conjunction with Neuralstem, Inc.

“We believe that injecting stem cells into the brains of diseased mice will have astonishing effects on memory and cognition,” said Eva Feldman, M.D., Ph.D., the study’s principle investigator and Director of the PNR&D. “By digging deeper into properties of these cells, we are now beginning to understand how that will happen and gaining knowledge which will ultimately allow us to apply those lessons to the human brain.”

PNR&D scientists have already advanced stem cell therapies to larger mammals and hope to conduct a human clinical trial on stem cell therapies for Alzheimer’s disease by 2018.

Alzheimer’s disease affects 5.2 million people in the United States, a number that is expected to double by 2050. Alzheimer’s disease is characterized by an accumulation of abnormal proteins in the brain which, over time, injure and kill brain nerve cells.  As the nerve cells are lost, so is a person’s ability to think, reason and function normally.


PNR&D scientists had a prolific month of publishing, including a review published in the Journal of the American Medical Association, the largest medical journal in the United States:

Electrodiagnostic Tests in Polyneuropathy and Radiculopathy. Callaghan BC, Burke JF, Feldman EL. JAMA. 2016 Jan 19;315(3):297-8. doi: 10.1001/jama.2015.16832.

Program scientists also published these articles in January:

The role of endoplasmic reticulum stress in hippocampal insulin resistance. Sims-Robinson C, Bakeman A, Glasser R, Boggs J, Pacut C, Feldman EL. Experimental Neurology. 2016 Jan 13;277:261-267. doi: 10.1016/j.expneurol.2016.01.007.

Antisense Oligonucleotides for Duchenne Muscular Dystrophy: Why No Neurologist Should Skip This. Jacobson RD, Feldman EL. JAMA Neurology. 2016 Jan 4:1-2. doi: 10.1001/jamaneurol.2015.4011. [Epub ahead of print] No abstract available.

Differential impact of type-1 and type-2 diabetes on control of heart rate in mice. Stables CL, Auerbach DS, Whitesall SE, D’Alecy LG, Feldman EL. Autonomic Neuroscience. 2016 Jan;194:17-25. doi: 10.1016/j.autneu.2015.12.006. Epub 2015 Dec 17.

PNR&D scientists close 2015 on a high note

Scientists in the Program for Neurology Research & Discovery published 22 articles in peer-reviewed scientific journals in 2015, and are starting 2016 with three more articles accepted for publication. Read the publications here:

2015 Feldman Laboratory Publications2

Here is a summary of the PNR&D’s ongoing work:

The role of inflammation in ALS pathogenesis

The goal of this project is to identify biomarkers that will allow us to diagnose ALS, better assess progression of the disease, and ultimately expand our understanding of how inflammation and the immune system contribute to ALS pathogenesis.

The role of epigenetic modifications in ALS pathogenesis

Our epigenetic research could enable insight into the mechanisms underlying sporadic ALS onset to facilitate the identification of effective therapies, early diagnosis, and potentially early-stage therapeutic interventions to increase survival outcomes in ALS patients.

Stem cell therapy for ALS

Dr. Eva L. Feldman is the PI of the first-in-human clinical trial investigating the use of intraspinal stem cell transplantation for the treatment of ALS. After Phase 1 results established safety of the stem cell transplantation surgeries, a Phase 2 trial investigated stem cell dosing and efficacy. In this trial, which began in September 2013 and was completed July 2014, 18 patients received increasing doses of cells ranging from 2 million to 16 million cells. Intraspinal transplantation of up to 16 million stem cells in patients with amyotrophic lateral sclerosis (ALS) was safe and well-tolerated, and caused no acceleration in disease progression. Due to these promising results we are currently planning the next Phase 2/3 trial.

Stem cell therapy for Alzheimer’s disease

Our long-term objective is to develop a breakthrough treatment for AD patients. Our approach combines the benefits of generating healthy new cells while protecting functional circuitry, thanks to a unique line of human stem cells we have developed in collaboration with Neuralstem, Inc. In preliminary experiments in animal models of early-onset AD, stem cells improved memory and cognitive deficits, of which even a modest improvement could significantly impact quality of life for a patient. Parallel studies are ongoing to determine exactly how these stem cells impact behavior, cognition and disease pathology in rodent models and to confirm safety in large animals, and will follow a similar preclinical pipeline to that used to bring our ALS stem cell therapy to trial. Within the next 18 months we aim to complete the necessary experiments to progress to an FDA-approved clinical trial in AD patients.

Alzheimer’s disease and diabetes

PNR&D investigators are studying the mechanisms underlying the interaction of these two pandemic diseases. Successful completion of these studies will give a fundamental basis for drug development and lifestyle modifications aimed at treating and/or preventing diabetes and Alzheimer’s disease. In a second project, scientists in the PNR&D are working to understand how obesity-related insulin resistance in neurons impacts cognitive impairment and Alzheimer’s disease pathology. A better understanding of this relationship will aid in the development of much-needed therapies to treat and prevent Alzheimer’s disease onset and progression in obese or diabetic individuals.

Diabetic neuropathy: basic science research

These studies are improving our understanding of how multiple complications develop and progress, determining biomarkers that reflect disease states and responsiveness to treatments, and enabling development of new comprehensive treatment strategies that target common pathways in diabetic complication-prone tissues that can be translated to patients. As part of an additional multi-investigator project, the PNR&D is examining energetic pathways involved in the onset of complications in nerve, kidney, and eye, in an effort to define changes in cellular metabolism that drive the development of diabetic complications. By studying neuronal changes in patients with diabetic neuropathy, we have discovered some of the key mechanistic pathways involved in neuronal injury during diabetes. These pathways have become the subjects for development of new, groundbreaking therapies.

Diabetic neuropathy: clinical research

We recently reported that diabetic neuropathy in type 1 and type 2 diabetes may result from differing pathogenic insults, as determined by reviewing results from a number of clinical trials evaluating glucose control. Additional clinical advances are being pursued through an interdisciplinary and collaborative translational project. Participation of the PNR&D in the International Diabetic Neuropathy Consortium (IDNC) is addressing the goals of 1) increasing the understanding of basic mechanisms and risk factors in diabetic neuropathy, 2) improving the detection and understanding of the clinical course of nerve damage in diabetes, and 3) eventually contributing to the prevention and treatment of diabetic neuropathy. The IDNC will ensure an in-depth analysis of basic, epidemiological, and clinical findings of diabetic neuropathy, and in addition provide a unique platform for educating future scientists/clinicians within the field.

In addition, Dr. Eva L. Feldman serves as a Co-Investigator on multiple type 1 diabetes trials, in addition to an ongoing clinical trial assessing an FDA-approved drug commonly used to treat osteoarthritis, to address inflammation – a critical mediator in the development and progression of peripheral nerve damage and pain in diabetes, which has recently been shown to have potential clinical benefit in diabetic neuropathy.

Dr. Hinder highlighted in ‘Neurology Today’

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.

[Read full story here]

Dr. Feldman presents ALS trial data at conference

Intraspinal transplantation of up to 16 million stem cells in patients with amyotrophic lateral sclerosis (ALS) was safe and well-tolerated, and caused no acceleration in disease progression, according to data presented by Dr. Eva Feldman at the American Neurological Association’s 2015 Annual Meeting in Chicago.

Additionally, 70 percent of patients recovered to higher levels than those of the historic control.

“The results of Phase I and Phase II are very encouraging, and we plan to move forward and expand this trial in 2016,” said Dr. Feldman, the Russell N. DeJong Professor of Neurology at the University of Michigan, as well as Director of the Program for Neurology Research & Discovery, Director of the A. Alfred Taubman Medical Research Institute, and Research Director of the University of Michigan Comprehensive ALS Clinic.

The data was collected through Phase I and Phase II of a trial that began in 2010. Phase II included 15 ambulatory patients with ALS. Participants were divided into five dosing cohorts with three patients in each, who received increasing quantities of cells in the cervical (upper) region of the spinal cord, ranging from two million to eight million cells. The fifth cohort received an additional eight million cells in the lumbar (lower) region.

The most common adverse effect of the stem-cell procedure was post-operative pain due to the surgery. One serious adverse event due to the surgical procedure was observed, but was not attributed to the cells themselves. The patient’s motor function was initially weakened, but then recovered to the patient’s ALS baseline.