Dr. Feldman authors review aimed at shifting worldwide diabetes research

March 22, 2017

Ann Arbor, Michigan – Breakthroughs in understanding the role of fats in the blood, energy transfer between cells, and whole-system analysis are providing clearer paths for researchers seeking therapies for diabetic neuropathy, according to a review written in part by Program for Neurology Research & Discovery (PNR&D) Director Eva L. Feldman, MD, PhD, and published today in the medical journal Neuron.

The review, which explores emerging insights into diabetic neuropathy, the nerve damage that is linked to diabetes, is a departure from earlier research that focused on blood sugars in understanding diabetic neuropathy. By turning their attention elsewhere, researchers are identifying potentially more effective targets for drugs to combat diabetic neuropathy, the leading cause of diabetes-related amputations.

The review was a multinational effort that included senior investigators Klaus-Armin Nave of the Max Planck Institute for Experimental Medicine in Gottingen, Germany; Troels S. Jensen of Aarhus University in Denmark; and David L.H. Bennett of the University of Oxford in the United Kingdom.

“By combining with key leaders in these various aspects of diabetic neuropathy research, we’ve highlighted recent game-changing advances that have redirected our approach to solving this common but vexing problem,” Dr. Feldman said. “By outlining these discoveries, we hope to reset the focus of diabetic neuropathy research and direct investigators toward new therapeutic targets. I’ve spent my entire career studying diabetic neuropathy. This is a very exciting time for the field.”

Recent technological advances have facilitated research that is examining entire human systems rather than isolated processes within the body. Using genome-wide profiling, investigators can look at entire systems to better understand how genes interact and activate body functions.

Additionally, recent research suggests that nerve damage from diabetes may result from alterations in the relationship between nerves and Schwann cells, the cells which normally protect and support neurons in the peripheral nervous system. Research under way at the University of Michigan has connected the effectiveness of this relationship with the level of lipids, or fats, in the bloodstream.

Because of these discoveries, future treatments for diabetic neuropathy may include targeting these emerging disease mechanisms with pharmaceuticals, in addition to more personalized treatment for each patient, the researchers said.

According to the Centers for Disease Control, more than 29 million Americans are living with diabetes and another 86 million are pre-diabetic, a condition that increases a person’s risk of Type 2 diabetes and other chronic diseases. Diabetes is caused by either an inability to generate insulin (Type 1) or an inability to use insulin properly (Type 2). Insulin allows sugars to be used by cells as energy; without effective insulin, sugars build up in the blood and can cause heart disease, stroke, blindness, kidney failure, and nerve damage which leads to amputation of toes, feet or legs.

PNR&D reach expands through research collaborations

The impact of the Program for Neurology Research & Discovery is amplified by a wide range of collaborations with researchers across the University of Michigan, the United States and the world.

Working with researchers outside the PNR&D not only allows access to much larger patient cohorts worldwide, but allows PNR&D scientists studying amyotrophic lateral sclerosis (ALS), Alzheimer’s disease (AD) and peripheral neuropathy to work across disciplines in an effort to gain a fuller, more integrated understanding of these diseases of the central and peripheral nervous systems.

Active collaborations include:

* In collaboration with Raymond Yung, MBChB, (U-M Department of Internal Medicine), we are applying a systems biology approach combining high-throughput profiling assays, qPCR, and pyrosequencing to determine whether miRNAs are altered in sporadic ALS.

* In collaboration with Sami Barmada, M.D., Ph.D. (U-M Department of Neurology) and Mats Ljungman, Ph.D. (U-M Department of Radiation Oncology, Comprehensive Cancer Center and Translational Oncology Program and the Department of Environmental Health Sciences, School of Public Health), we are identifying common and unique dysregulated mature miRNA changes in patient-derived fibroblasts from sporadic ALS and C9orf72 ALS subjects using NanoString technology.

* An additional collaborative project with Sami Barmada is also under way, and is focused on differentiating iPSC lines from ALS-patient and healthy control fibroblasts into neurons to assess differential miRNA expression, cell phenotype, and cell survival using Longitudinal Fluorescence Microscopy imaging technology.

* In collaboration with Sunitha Nagrath, Ph.D. (U-M Department of Chemical Engineering), we are determining the biological role and clinical relevance of circulating exosomes in ALS pathology by isolating and quantitating circulating and brain exosomes to characterize the molecular cargo from ALS and healthy control human samples.

* In collaboration with John Kao, M.D. (U-M Department of internal Medicine), we are correlating differences in microbiota diversity in the intestinal system of patients with the development of ALS.

* In collaboration with Tatiana Botero, D.D.S., M.S. (U-M Dental School), Manish Arora, B.D.S, M.P.H., Ph.D. (Mount Sinai Hospital, New York, Department of Preventative Medicine), and Stuart Batterman, Ph.D. (U-M School of Public Health), we are identifying aberrant concentrations and/or absorbance patterns of trace elements in permanent sALS teeth that could be associated with environmental/occupational exposures or nutritional factors leading to sALS.

* In collaboration with Stephen Goutman, M.D. (U-M Department of Neurology) and the Michigan Institute for Clinical & Health Research, we are identifying upregulated pro-inflammatory immune cell populations that correlate with ALS disease progression. The goal is to ultimately identify potential biomarkers or therapeutic targets of disease.

* In collaboration with Brad Foerster, M.D. (U-M Department of Neurology), we are using PET scans to assess macrophage activation levels in the CNS of ALS versus healthy and correlating these data with markers of inflammation in the peripheral blood.

* In collaboration with Nils Walter, Ph.D. (U-M Department of Chemistry), we are using high-resolution single-molecule fluorescence imaging to evaluate miRNA dysregulation and determine whether aberrant interactions between miRNAs and ALS-hallmark protein aggregates disrupt epigenetic homeostasis in the nervous system and lead to the progression of ALS.

* In collaboration with Ben Reubinoff, M.D., Ph.D. (Hadassah Medical Center, Israel), we are developing iPS cell lines from patients with familial and sporadic ALS to study pathogenic disease mechanisms and test therapies.

* In collaboration with Neuralstem Inc. (Germantown, MD), we are developing novel cellular therapies for ALS and AD based on Neuralstem’s human neural stem cell lines. Specific projects include identifying optimal stem cell lines for pre-clinical testing, and utilizing stem cells in rodent models to determine the efficacy of stem cell treatment. Additional projects include examining the effect of the drug NSI-189 on cognitive and biochemical changes in the brains of high fat-fed mice.

* In collaboration with Geoff Murphy, Ph.D. (U-M Molecular and Behavioral Neuroscience Institute), we are determining the impact of our NSC therapies on AD-related cognitive deficits of AD mice. Specific tasks include establishing a battery of well-characterized hippocampal-dependent behavior tasks that will enable the evaluation of clinically relevant measures of cognition such as learning and memory, providing important data required by the FDA for future clinical translation of our lead NSC candidates. Additional studies in collaboration with Dr. Murphy include using behavioral tests to examine the effects of high fat feeding and specific drugs on mouse cognition.

* In collaboration with Cindy Chestek, Ph.D. (U-M Department of Biomedical Engineering) and Parag Patil, M.D., Ph.D. (U-M Department of Neurosurgery), we are devising methods to optimize MRI-guided stereotactic stem cell transplantation techniques to the peri-hippocampal region of the brain. This will allow us to ensure the safety of our approach, enabling rapid translation to early phase trials in patients.

* In a collaboration with Peter Scott, Ph.D. (U-M Department of Radiology and Nuclear Medicine), we are testing several novel PET tracers in our AD mouse models to identify a longitudinal biomarker that can be easily translated to AD patients.

* In collaboration with Julia Raykin, Ph.D. (Georgia Institute of Technology), we have received high-throughput, customized, and target-specific quantitative image analysis techniques to measure AD related pathologies in tissue.

* In collaboration with Charles Burant, M.D., Ph.D. (U-M Department of Computational Medicine & Bioinformatics; The Michigan Regional Comprehensive Metabolomics Resource Core), Subramaniam Pennathur, M.B.B.S. (U-M Department of Internal Medicine; Nutrition Obesity Research Center Molecular Phenotyping Core), Frank Brosius III, M.D. (U-M Department of Internal Medicine and Molecular and Integrative Physiology), Matthias Kretzler, M.D. (U-M Department of Internal Medicine, Computational Medicine and Biology), and Thomas Gardner, M.D., M.S. (U-M Department of Ophthalmology and Visual Sciences), we are using the BKS db/db mouse model of type 2 diabetes to investigate changes in carbohydrate and lipid metabolism in kidney cortex, peripheral nerve, and retina. Our systems approach using transcriptomics, metabolomics, and metabolic flux analysis aims to identify tissue-specific differences in glucose and fatty acid metabolism.

* In collaboration with Subramaniam Pennathur, M.B.B.S. (U-M Department of Internal Medicine; Nutrition Obesity Research Center Molecular Phenotyping Core), Frank Brosius III, M.D. (U-M Department of Internal Medicine and Molecular and Integrative Physiology), and Matthias Kretzler, M.D. (U-M Department of Internal Medicine, Computational Medicine and Biology), we are also identifying lipid biomarkers that lead to the onset diabetic kidney disease, diabetic neuropathy, and diabetic retinopathy in order to elucidate the essential cellular lipid metabolism responses that are amenable to novel therapies.

* In collaboration with Brian Callaghan, M.D. (U-M Department of Neurology), Morten Charles, M.D., Ph.D. (Aarhus University, Aarhus, Denmark), Troels S. Jensen, M.D., D.M.Sc. (Aarhus University), and Reimar W. Thompson, M.D., Ph.D. (Aarhus University), for the International Diabetic Neuropathy Consortium (IDNC), we are addressing the goals of 1) increasing the understanding of basic mechanisms and risk factors in DN, 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 DN. The IDNC will ensure an in-depth analysis of basic, epidemiological, and clinical findings of DN, and in addition provide a unique platform for educating future scientists/clinicians within the field.

* In collaboration with Sebastian Parlee, Ph.D. (U-M Department of Physiology) and Michael Dority (U-M Medical School Host Microbiome Initiative), we are using the mouse dietary reversal model to explore the role of pathophysiological local adipose tissue remodeling in HFD-induced neuropathy as well as the role of changes in the intestinal microbiome and their impact on peripheral nerves.

* In collaboration with Celine Berthier, Ph.D., Eddy Sean, Ph.D., and Felix Eichinger, Ph.D. (U-M Department of Internal Medicine), we are using an unbiased bioinformatics clustering method to examine the tissue-specific effects of drugs on the nerves and kidneys during type 2 diabetes.

* In collaboration with Janet Shaw, Ph.D. (University of Utah, Department of Biochemistry), we are studying the involvement of Miro1 and Miro 2 proteins in abnormal mitochondrial trafficking associated with palmitate treatments.

* In collaboration with Guido Cavaletti, M.D. (University of Milan Biccoca, Department of Surgery and Translational Medicine) and Cristina Meregalli, Ph.D. (University of Milan Biccoca, Department of Surgery and Translational Medicine), we are utilizing mitochondrial trafficking techniques to test the efficacy of chemotherapeutic agents.

* In collaboration with Marija Sajic, Ph.D. (University College London, Department of Neuroinflammation), we are evaluating changes in mitochondrial transport in saphenous nerve axons of mice, and also plan to apply this technique to the high fat mouse model.

* In collaboration with Jorge A. Iñiguez-Lluhí, Ph.D. (U-M Department of Pharmacology), we are examining post-translational modifications in the CNS to determine the role of alterations in SUMOylation and ubiquitination in the pathogenesis of sensory neuron degeneration.


Teaming up to #IceALS

Ann Arbor – A new awareness campaign to support ALS patient care and research picks up right where the Ice Bucket Challenge left off: On ice.

With fans chanting “Ice ALS,” Michigan’s hockey, research and clinic teams, along with the ALS Association’s Michigan Chapter, all came together on October 8 to defeat a common opponent: amyotrophic lateral sclerosis, also known as Lou Gehrig’s disease or ALS.

10/8/16 2016-17 Men's Ice Hockey defeats Union College. IHM 2016-17 Win 4-0

The event, held at Yost Ice Arena, was part of the University of Michigan’s 4-0 hockey victory over Union College. It included former Michigan hockey player Scott Matzka, as well as Joe Feudi, whose wife Jill is the business operations manager for Yost Arena. Families of both Matzka and Feudi participated; Matzka dropped the ceremonial first puck to start the game. Both men are ALS patients.

The event was also attended by PNR&D Director Eva L. Feldman, MD, PhD, an eminent ALS researcher; Stephen A. Goutman, MD, Director of the U-M’s Comprehensive ALS Clinic; and Paula Morning, Executive Director of the ALS Association’s Michigan Chapter, all of whom wore #IceALS t-shirts.

10/8/16 2016-17 Men's Ice Hockey defeats Union College. IHM 2016-17 Win 4-0

The event was designed to raise awareness of ALS, a degenerative disease that causes nerve cells to die. ALS patients first experience weakness in their muscles, but eventually lose their ability to eat and breathe. There is no known cure.

“The 2014 Ice Bucket Challenge drew a lot of national attention to ALS,” Dr. Feldman said. “But we still have a long way to go to raise awareness and funding for ALS research. So we’ve taken to the ice again – in a different way – to keep ALS in the public eye.”

The University of Michigan’s ALS Clinic provides multidisciplinary care for ALS patients that includes respiratory, physical and occupational therapy to help patients live independently for as long as possible; nutritionists to keep them strong; a social worker to help families identify and secure needed resources; and even a wheelchair specialist.

“We’re so grateful to these U-M hockey families touched by ALS for everything they’re doing,” continues Feldman. “They are truly remarkable. They’ve received this diagnosis so bravely, and they’re out here advocating and inspiring all of us to keep up the fight to ice ALS.”

See the related U-M Health blog here.

Ice ALS! campaign kicks off Saturday in Yost Arena

Wolverines ice hockey team to promote awareness of Lou Gehrig’s disease

Ann ArborIce ALS!  

That’s the slogan of a new grass-roots advocacy campaign that will kick off Saturday with help from the University of Michigan Wolverines ice hockey program.

It’s inspired by the efforts of U-M alum Scott Matzka, who was diagnosed with ALS (amyotrophic lateral sclerosis) a year ago.   He was not long retired from an 11-year professional hockey career, which was preceded by four years with the Wolverines, including the team’s 1998 NCAA championship season.

Since then, the father of two has advocated for increased funding and research into ALS. Public knowledge and contributions took off in 2014 during the viral Ice Bucket Challenge, and supporters hope to engage a new audience if Ice ALS! spreads throughout the hockey community.

Eva L. Feldman, MD, PhD, the renowned U-M physician-researcher who is running the first-ever trial of a stem cell treatment for ALS, will be at the game with colleagues in ALS research. She will be joined by Stephen Goutman, MD Clinical Director of the U-M ALS Clinic.

“We have been so privileged to care for Scott,” said Feldman, Research Director of the U-M ALS Clinic and head of the A. Alfred Taubman Medical Research Institute. “We need to honor him and the many other brave patients like him by dedicating more resources to developing therapies for ALS.   The Ice Bucket Challenge was a great boost to medical research – now let’s all join together to completely Ice ALS!”

On Saturday, October 8, Matzka will drop the ceremonial puck at historic Yost Arena as the U-M ice hockey team faces off against New York’s Union College Dutchmen.

Matzka’s appearance is part of the Wolverine’s ALS Awareness event, which also will feature researchers and advocates for patients with the disease, kicking off “Ice ALS!” The team also will honor another former U-M player, Jim Ballantine, who passed away from ALS. All players will be wearing special patches for this game featuring a block M, ALS awareness ribbon and Scott and Jim’s jersey numbers.

A photo booth will be available for fans to pose and show their support for ALS, and fans may tweet photos to appear on the Yost Arena videoboard.

Feldman and Paula Morning, chief executive officer of the ALS Association Michigan Chapter, will be on hand before and during the match to talk with fans about the latest in ALS research and advocacy, and suggest how new supporters can get involved.

“The ALS Association Michigan Chapter board and staff, in its 28 year history of serving Michigan’s ALS population, is grateful for this opportunity,” said Morning. . “We are most delighted to be a part of this ALS Awareness Night. It is certainty a milestone in the effort to “Ice ALS” as we work to ‘Stop ALS Cold!’ through care, advocacy and research.”

Game time is 5 p.m. Tickets may be purchased online or by contacting the U-M Athletic Ticket Office at (734) 764-0247 or (866) 296-MTIX.

PNR&D continues collaborative mission in India

The Program for Neurology Research & Discovery’s mission of worldwide collaboration continued this summer, connecting Mount Pleasant, Michigan, with Chennai, India, through the work of medical students Sam Jackson and Mutshipay Mpoy.

The pair, rising second-year students in the Central Michigan University College of Medicine, traveled to India as part of a University of Michigan-led team of medical researchers working to improve the understanding and treatment of diabetes.

Sam Jackson, left, and Mutshipay Mpoy in Ann Arbor.

Sam Jackson, left, and Mutshipay Mpoy in Ann Arbor.

The study is led by PNR&D Director Eva Feldman, MD, PhD, a world-renowned leader in the field of diabetic neuropathy. Jackson’s work in diabetic neuropathy began as a U-M undergrad, when he began working with Dr. Feldman in the PNR&D. Mpoy, who was born in the Democratic Republic of Congo and fled to the United States as a refugee in 2000, has always had a passion to improve and care for underrepresented communities internationally.

The study is being conducted in collaboration with Dr. Vijay Viswanathan, director of the MV Diabetes Hospital in Chennai. Its goal is to improve understanding the mechanism of diabetic neuropathy – or nerve damage – the most common complication of diabetes.

According to Jackson, one of the interesting findings seen in the clinic is that patients may present with neuropathy without having full-on diabetes. Many patients develop this complication in what’s known as the pre-diabetic state, indicating that there may be other factors contributing to the progression of the nerve damage. In order to better understand this, this team of scientists has been screening patients in this early state of diabetes, looking not only at their sugar levels, but also other metabolic parameters including blood pressure, waist circumference, and various fat levels in their blood in order to identify other clues that may be factors in the development of this devastating disease.

“I’ve been repeatedly asked a very important question by my friends and family, ‘Is diabetes even a problem over there?’” Jackson said. “And the resounding answer is, ‘YES!”

Jackson said India reported more than 69 million cases of diabetes in 2015, more than double the U.S., which has around 30 million. One estimate shows that more than 1 million Indians die due to diabetes each year, and the problem seems to be getting worse. Due to poverty and certain cultural practices, the complications of diabetes seen in India can be more extreme than often seen elsewhere. Many people in India walk barefooted, which can be especially dangerous for people with diabetic neuropathy who cannot feel any pain if they cut or burn a foot. Additionally, bacteria love the excess sugar found in diabetic wounds, so infections of these undetected ulcers are very common. Diabetes also damages the blood vessels making it difficult for the body to transport blood and immune cells to the injury to naturally heal the wound. On top of all of this, many of the patients are extremely poor and avoid seeking medical treatment until absolutely necessary. This combination of loss of sensation, increased infection, impaired wound healing, and inability to access health care often add up to amputation, Jackson said.

By gaining a better understanding of diabetes and its complications, health care workers in the India as well as the U.S. can better predict and prevent serious complications such as these.

“Being able to see and experience what the health care system is like in India has been very eye opening,” Jackson said. “I did not grow up thinking I would be doing this kind of medical work abroad, but now I am more motivated than ever to do well in order to go back there. It really has been a life changing experience for me.”

Mpoy agreed.

“This experience has rekindled my love for medicine, reaffirming why I decided to go into medicine in the first place. It has reinforced my desire to work overseas in global health.”

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 http://www.crainsdetroit.com/awards/mostinfluentialwomen/2016.

Taubman Institute Art+Science featured in The Detroit News

Click here to read about the Taubman Institute’s Evening of Art + Science.