Dual MRI technique leads to more accurate ALS diagnosis

A technique that uses two different types of magnetic resonance imaging (MRI) on the brain can more accurately diagnose amyotrophic lateral sclerosis  (ALS) than using a single type of MRI alone, a finding that could lead to earlier diagnoses of the deadly disease and ultimately to more effective treatments for patients. (Watch video here)

The study, “Multi-modal MRI as a Diagnostic Biomarker for Amyotrophic Lateral Sclerosis,” was performed by a research team from the University of Michigan’s Program for Neurology Research & Discovery, led by University of Michigan neuro-radiologist Bradley R. Foerster, M.D., Ph.D., an Emerging Scholar in the A. Alfred Taubman Medical research Institute.

Dr. FoersterThe article was published in the open-access Annals of Clinical and Translational Neurology, an official journal of the American Neurological Association.

The diagnosis of ALS, also known as Lou Gehrig’s Disease, is challenging to physicians because different patients show a wide range of symptoms. By adding proton magnetic resonance spectroscopy to diffusion tensor imaging, researchers found that diagnostic accuracy was significantly improved over that of DTI alone. Researchers hope that multi-modal MRI can help them identify biomarkers specific to ALS, and in earlier stages of the disease.

“We’re going to enroll patients with earlier-onset disease,” Dr. Foerster said. “And then we’re also going to include patients with other types of disease to make sure we have a signature that’s specific. What we’re trying to do is create an imaging fingerprint of this disease, just like you have a fingerprint that’s unique to you.”

In the study, Foerster and his team compared 29 ALS patients with 30 age- and gender-matched healthy controls. The subjects underwent brain MRI that collected thousands of data points, which Foerster and his colleagues will use to identify imaging characteristics of patients with early ALS.

“Analyzing this data is quite challenging,” Dr. Foerster said. “We’re trying to hone down the statistical models to say ‘what are the definitive characteristics of this imaging set for these disease patients?’”

ALS is a debilitating motor neuron disease that causes the loss of nerve cells in the brainstem and spinal cord that control movement. Also known as Lou Gehrig’s disease, it usually strikes people in midlife and is relentlessly progressive, typically resulting in death within five years of the first sign of symptoms. Patients lose the ability to control their limbs, facial muscles, swallowing, and eventually, the ability to breathe. While the causes of ALS are largely unknown, most cases likely arise through a combination of genetic factors and environmental stress.

Cross-discipline research can help researchers expand their understanding of disease mechanisms and treatment, according to Eva Feldman, M.D., Ph.D., Director of the Program for Neurology Research & Discovery and the A. Alfred Taubman Medical Research Institute, both at the University of Michigan.

“These types of collaborations are extremely important to the work we’re doing in our lab and in the Taubman Institute,” Dr. Feldman said. “By working with researchers in other areas, like Dr. Foerster, we can really expand the scope of our discovery. And that ultimately leads us more quickly to more effective treatments for patients of neurologic diseases like ALS.”

The Program for Neurology Research & Discovery (PNR&D) is the laboratory of Dr. Eva Feldman, M.D., Ph.D., the Russell N. DeJong Professor of Neurology at the University of Michigan Medical School and the director of the A. Alfred Taubman Medical Research Institute. Under Dr. Feldman’s direction, the PNR&D’s 30-plus scientists, clinicians, and students are working toward the common aim of understanding and curing neurological diseases.

Dr. Feldman is the principal investigator for a national phase 2 clinical trial that has injected millions of stem cells into the spinal cords of seven ALS patients in an effort to slow or stop the progression of ALS.

Foerster’s research is in part supported by an Emerging Scholar Grant from the A. Alfred Taubman Medical Research Institute.  Emerging Scholar grants are intended to help  junior clinician-scientists at the University of Michigan make progress in their medical research while establishing the credentials required to obtain funding from more traditional sources.

Feb. 5 Health Science Lecture Postponed

The Feb. 5 Health Science Lecture that was scheduled to be delivered by Steven L. Kunkel, Ph.D., the senior associate dean for research at the University of Michigan Medical School, was postponed due to inclement weather. The new date for Dr. Kunkel’s lecture will be posted here as soon as it is scheduled.

About the lecture series: The Health Science Lecture Series is sponsored by the A. Alfred Taubman Medical Research Institute, the Program in Biology and a number of student organizations. The lectures are held quarterly on the U-M campus and focus on a wide variety of topics including medical research, public health, bioethics, evolutionary biology, epidemiology and many others.

The next event is scheduled for March 22, with Parag Patil, M.D., Ph.D., the U-M Medical School neurosurgeon who is performing the intraspinal stem cell injections for ALS patients participating in Dr. Eva Feldman’s landmark trial of a stem cell therapy for that disease.

ALS stem cell trial reaches milestone: 25th stem cell injection

ANN ARBOR, Mich. — A patient with amyotrophic lateral sclerosis (ALS) received six million stem cells injected to the spinal cord in a procedure Jan. 8 at the University of Michigan Health System – the 25th time an ALS patient has undergone the experimental injections as part of a national clinical trial.

The 66-year-old man has returned home and will receive follow-up monitoring and testing to help U-M neurologists assess the safety and any potential effect of the injections. He is the 7th patient to undergo the surgery in Phase 2 of the trial, which began in September and follows a 15-patient Phase 1 trial that produced no adverse side effects in patients undergoing the surgery.

Eva L. Feldman, M.D., Ph.D., the Russell N. DeJong Professor of Neurology at the U-M Medical School and director of the A. Alfred Taubman Medical Research Institute, is the principal investigator for the trial. Feldman has led the analysis of results from the Phase 1 trial which concluded in 2012.

In Phase 1, three of the 15 patients received a second injection of stem cells, for a total of 18 surgeries in that segment of the trial.  The seven surgeries so far in Phase 2 bring the total number to 25.

“We’re pleased that as we reach this important milestone, none of our patients in either phase of the trial have experienced any adverse side effects as a result of the stem cell implantation,” said Feldman.  “We are very excited to note that escalating the number of stem cells per patient does not appear to increase that risk.”

In data presented in 2013, spinal cord injections of between 500,000 to 1.5 million cells were delivered safely and tolerated well in a Phase 1 trial conducted at Emory. The researchers reported possible signs that in one subgroup of participants who received the highest dose of stem cells, ALS progression may have been interrupted.

Additional patients with the condition, also known as Lou Gehrig’s disease, are being evaluated for possible participation in the trial at U-M and Emory University. Patients in the Phase 2 trial will receive up to 16 million of the specially engineered stem cells.

The Phase II trial is approved by the U.S. Food and Drug Administration and funded by Neuralstem, Inc., the Maryland-based company whose stem-cell product the trial is testing. It seeks to study any effect that injected stem cells might have on motor neurons – muscle-controlling nerve cells that die in ALS patients, eventually robbing them of the ability to walk, speak and breathe.

Parag Patil, M.D., Ph.D., a U-M neurosurgeon and biomedical engineer, performed the four operations that have been completed at U-M. In each case, the patient’s spinal column was unroofed and the spinal cord exposed to receive the cells. The cells are introduced via a custom-designed delivery device that is affixed to the subject’s spinal bones so that it moves with the patient’s breathing throughout the process.

Patil, an assistant professor in U-M’s departments of Neurosurgery, Neurology, Biomedical Engineering and Anesthesiology, and a Young Friends of the Taubman Institute Emerging Scholar, also serves as a paid engineering consultant to Neuralstem to further develop the cell-delivery device.

This Phase 2 dose escalation trial is designed to treat up to 15 ambulatory patients in five different dosing cohorts, under an accelerated dosing and treatment schedule.

The first 12 patients, divided into four cohorts, will receive injections only in the cervical region of the spinal cord, where breathing function is controlled. The first cohort of three patients received 10 cervical region injections of 200,000 cells per injection. The second cohort of three patients received 20 cervical region injections of 200,000 cells per injection. The trial has now progressed to the third cohort of three patients receiving 20 cervical injections of 300,000 cells per injection.  If this proves safe, the fourth cohort will receive 400,000 stem cells per injection with  20 cervical injections.

The last three Phase 2 patients will receive injections in both the cervical and the lumbar spinal regions.  These patients will receive 20 injections of 400,000 cells each in the lumbar region in addition to the 20 injections they will already have received in their cervical region.

The trial also accelerates the treatment schedule, and is designed to progress at the rate of one cohort per month with one month observation periods between cohorts. Researchers expect all of the patients could be treated by the end of the second quarter in 2014.

Patients seeking information on the trial should contact the relevant center. For the University of Michigan Health System, please visit: http://www.umclinicalstudies.org/HUM00072488. For Emory Healthcare, please call (404) 778-7777.

For more information on ALS treatment and research at the U-M Health System, visit http://umhealth.me/UM-ALS .

Generous donors fund institute’s summer interns

TaubmanSummerInternsPhilanthropy fuels the Taubman Institute’s mission of funding talented, proven clinician-scientists at U-M, and their promising junior counterparts, through grant programs that support these physicians’ laboratory research.

And now, generous donors have made it possible to teach and encourage the medical science leaders of tomorrow.  Michigan philanthropists Joel and Shelley Tauber, longtime U-M supporters and members of the Taubman Institute’s Leadership Advisory Board, are the benefactors of the institute’s newest initiative, the Tauber Family Student Internship Program.

This five-year financial commitment will finance three student internships each year, allowing undergraduate students to work within the laboratories of Taubman Scholars or Emerging Scholars.  It’s hoped that the exposure to cutting-edge translational medical research will encourage these budding scientists to choose a lifetime of striving to bring new cures and treatments to patients with difficult diseases.

“When young, imagining a future for oneself can be overwhelming,” the Taubers said.  “We want to be part of inspiring young people to pursue a future in medical research by exposing them to Michigan’s scientific environment.

“Our goal is to enable interested and qualified young students to be part of teams that are focused on understanding and advancing medicine and its ability to treat disease.”

For 2013, three students will assist in the Program for Neurology Research & Discovery, the laboratory of Taubman Institute Director Dr. Eva Feldman.  They are:

  • Anna Bakeman, a student at the Medical College of Wisconsin
  • Rebecca Glasser, a student at Harvard University
  • Sangri Kim, a student at Johns Hopkins University

All of the interns will have an opportunity to work on projects ranging from stem cell derivation to the analysis of skin samples taken from neurology patients.

Rebecca Glasser, a West Bloomfield, Mich. native and a sophomore studying molecular and cellular biology at Harvard, says the internship meshes with her career aspiration to work as a clinician-scientist.

Working in the lab is a manifestation of everything I’ve learned in school,” she said.  “It’s great to actually see how everything comes together in the lab, rather than just in a textbook.  It’s really given me perspective on what I want to do.

Crain’s: Man who received ALS stem cell transplant still doing well

TedHaradaTed Harada, a 40-year-old man diagnosed with ALS, who received stem cell implantations to his spinal cord in two separate surgeries as part of the first-ever FDA-approved trial of a stem cell therapy for ALS, talked last week with Crain’s Detroit business reporter Tom Henderson.  Harada said he’s still feeling the positive effects he attributes to his second surgery, which took place last August.

“I’ve been doing great and feeling great.” Harada told Henderson. “Just now, the left leg showed a little bit of weakness returning, but I’m still so much better than I was before the surgeries. It’s the first time, since August, they’ve noticed any slight weakness.

“It’s clear from the data that the injections reversed my symptoms and slowed down the progression of the disease. I’ve received a blessing. I almost forget I have ALS. I don’t have the constant reminder of having to use the canes. Now, I don’t think about ALS every day. Every couple of days something happens and I think, `Oh, yeah, I have ALS.’ ”

Taubman Institute Director Dr. Eva Feldman received FDA approval in April to move the trial to Phase II, which will study efficacy as well as safety.  Patient recruitment has not yet started for that phase of the trial.

Click here to read the entire Crain’s blog post.

Women Talk Health with Women

Women’s Health & Fitness Day provides a heavy dose of good advice

Women often interact with doctors only when they’re sick. At least once a year, women students in the University of Michigan’s Medical School seek to change that by holding an annual Women’s Health & Fitness Day.

Women often interact with doctors only when they’re sick. At least once a year, women students in the University of Michigan’s Medical School seek to change that by holding an annual Women’s Health & Fitness Day.

This year on January 24, more than 225 women jammed Ypsilanti High School to hear from a wide variety of health-care professionals about how they could lead healthier, happier, more productive lives.

Seventeen medical students and more than 20 community leaders volunteered their time to make this free event possible. It was funded, in part, by the Program for Neurology Research and Discovery.
The day began with a free breakfast and a round of yoga. Then, participants took part in 19 workshops on topics such as depression, sexuality, obesity, financial health and stress management. The sessions were taught by University of Michigan Health System doctors, nurses, physical therapists and nutritionists.
The program culminated with a rousing talk by Sheila Taorima, the Olympic champion from Michigan, who recently founded Friendsport, a nonprofit organization that seeks to inspire Americans to adopt healthier lifestyles.

“The day was a success with many great worksops and Sheila Taormina’s inspiring keynote,” said Cassandra Niemi, co-director of the event with Lane Frasier. “It was wonderful to talk with so manny women who were energized by new friends and by the knowledge they gained from health-care professionals.

Beyond the Laboratory

Beyond the Laboratory

Sponsor Steve Sarns from NuStep and Becca Schumaker, Michigan Regional Director of the Muscular Dystrophy Association, join Dr. Eva Feldman in the Big House at the end of the race.

None of our progress would have been possible without the thousands of people who donate their time, money and hard work to support the Program for Neurology & Discovery.

A Run for the Research Money

On Sept. 28, the Big House Big Heart event drew 7,000 runners and walkers to the U-M stadium, where they got to watch themselves cross the 50-yard-line on the stadium’s Jumbotron. Nearly $250,000 was raised for charity. Two great U-M causes were the primary recipients: The Program for Neurology Research & Discovery and the C.S. Mott Children’s Hospital.

The man with the biggest heart is local attorney Mike Highfield, who started the run in 2007 after watching Phil Bowen, his friend and law partner, pass away from ALS. He and sponsor, Running Fit, have made this an instant fall tradition.

Next year’s date has already been chosen: October 4. For more information, visit the Big House Big Heart Web site.

A Community Fights Back

A Community Fights Back

Gretchen Spreitzer and her husband Bob Schoeni thank all those who participated in this year’s A2A3 Family Field Day.

When Dr. Bob Schoeni was diagnosed with ALS this summer, it was a shock to friends, colleagues and family in the Ann Arbor community. A popular U-M professor Bob has touched a lot of lives, especially through his coaching of girls sports. A large number of Ann Arbor girls call him simply, “Coach Bob.”

When his friends and coworkers heard about his condition, they organized a non-profit, A2A3 (Ann Arbor Active Against ALS), to support ALS research. Some of their initiatives include Training for a Cure, Coaching for a Cure, and Kids Active for a Cure. They have held a garage sale and Family Field Day.

A portion of the proceeds will go to ALS research at the Program for Neurology Research & Discovery. For information, go to www.a2a3.org.

Stem Cells and Salads

Stem Cells and Salads

Dr. Feldman with the hosts of the luncheon (from left): Pamela Applebaum, Susu Sosnick and Leslie Lewiston Etterbeek.

Along with co-hosts Susu Sosnick and Pamela Applebaum, Leslie Lewiston Etterbeek invited Dr. Feldman to her Bloomfield Hills home to talk to 45 guests on October 3 about stem cell research and the promise it holds for finding new treatments and cures for neurological disease.

Feldman explained what makes embryonic stem cells so special and the work she hopes to be able to do at the University of Michigan if such research became legal in the state. Just one month later, the voters of Michigan passed a new law lifting the ban on stem cell research.

Charity Event Par Excellence

League chairs are recognized at this year's tournament.

League chairs are recognized at this year’s tournament.

For the past seven years, the Executive Women’s Golf Association of Metro Detroit has conducted an end-of-season tournament to raise money for the Program for Neurology Research & Discovery. This year’s event took place on September 25 at Twin Lakes Golf Club in Oakland Township.

Nearly 60 people teed off. The golfers, sponsors and a silent auction raised $2,400 for neurological research. The EWGA exists to provide a setting for women to learn to play and enjoy the game of golf for business and pleasure. The Metro Detroit Chapter has over 200 members in Oakland, Macomb, Wayne and Washtenaw counties.