Why Is Research Important
By Kenneth Casey M.D., FACS
Clinical Associate Professor of Surgery (Neurosurgery) Michigan State University SOM
Clinical Associate Professor of PM&R Wayne State University SOM
Surgical Director Intensive Care Oakwood Southshore
Have you ever gotten up in the morning and been very excited about the prospects for the day? You’ve have a new friend to meet or you’re going on a trip to an area you’ve never been or you’re going to revisit and reconnect with an old friend. All these are exciting because something new is going to happen, something different, and you’re going to come away with new feelings and different perspectives. Research is exactly like that. The origin of the word from the old French says exactly that, that you’re going to look very intensively for something( Old Fr. recherche).
Researchers get involved because they get excited about something that’s not known or something that’s not completely explained and they dedicate literally years of their lives, days of their weeks, and hours of their days trying to find these bits of information. What’s even more fun for a researcher though, is finding other pieces of information, little sidebars as it were, that were not known before. These sidebars are important ,not as a detour, but as an increasing amount of knowledge that’s adding to the general fund of things we know and things we can work with in our lives. People talk about the fact that research is important in medicine because it makes it possible for some cures or some improved treatments and that’s certainly the case with the Facial Pain Research Foundation. It means much more than that because if we can find how something works, whether it be something in our own body or something outside our body in the atmosphere or something outside ourselves beyond the planet, we’re going to be that much richer for the experience. We also know that research allows us to understand several sides of a given question.
For years the world was flat and everyone believed you could sail off the end. Researchers and explorers showed that based on their calculations from the time of Galileo and da Vinci to the times of Columbus and other explorers that that’s not true. It is a circle of land, water, and people. The world exists as a collected community. Research can provide truth and put paid to certain mistruths or errors in knowledge that may hold us back and may stop us from going in the right directions. It’s a way to support day to day life and to support fundamental truth.
Research offers us all an opportunity to pursue more each day when we get up and when a researcher puts together a hypothesis and begins the steps to take that hypothesis piece by piece and develop it into a theory and the theory translates into practice, every single one of us will benefit.
Research is important because we go back and search again through what’s happened and look again at what has already been written down and done and with a very critical eye and an unparalleled intensity, we ask what more can we do, what more can we accomplish, what more can we learn.
Editor’s Note
Todd E. Golde, M.D., Ph.D., is executive director of the Evelyn F. and William L. McKnight Brain Institute of the University of Florida. He oversees neuroscience and neuromedicine research programs across the University of Florida campus. A professor of neuroscience and neurology, Dr. Golde joined the University of Florida faculty in 2009 and became founding director of the university’s Center for Translational Research in Neurodegenerative Disease, which he led until taking charge of the McKnight Brain Institute in December 2016. He is also director of the NIH funded 1Florida Alzheimer’s disease Research Center group of institutions.
An internationally known expert in the scientific understanding of Alzheimer’s disease, Dr. Golde has published more than 240 papers that have been cited more than 30,000 times, (https://scholar.google.com/citations?user=X_9xacsAAAAJ&hl=en), and has expanded his leading-edge research to include other neurodegenerative diseases, cancer and even malaria. He is lead investigator for the Facial Pain Research Foundation’s Gene Therapy Research Project, at the University of Florida, to find the cures for TN.
Dr. Golde spoke with Mervyn Rothstein, who was a writer and editor at The New York Times for nearly 30 years and now writes the Stage Directions column – a series of interviews with theater directors – for Playbill.com. His first symptoms of trigeminal neuralgia occurred in 2005.
Mervyn Rothstein Interviews
Todd Golde
How and why did you become Involved In the “World” Of Scientific Research?
TG: I’ve loved biology from as far back as I can remember. The real catalyst was when I was in my junior year in college. I didn’t know what I was going to do. I was thinking about going back and teaching at a boarding school for a while before I figured out what I was going to do with my life. But I was a biology major at Amherst College and I took a course with a professor named Richard Goldsby, a wonderful teacher, who was basically teaching a graduate level course to undergraduates. We had to write a term paper, a research-hypothesis type paper, the first time I’d had to do that in college, and the response back was that this was one of the best papers he’d read in many years, undergraduate or graduate. Please come talk to me. I think you might like to do research.
Your laboratory conducts disease oriented research with specific, but not exclusive focus on neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. How did you get involved in developing a research project to find a cure for Trigeminal Neuralgia and related neuropathic pain?How did the development of this research project come about, and what motivated you to take on the leadership role?
TG: I make no claims about being a facial pain or trigeminal neuralgia expert. I’m just thinking opportunistically about how we can make a difference. When I came to the University of Florida, I was the founding director of the Center for Translational Research in Neurodegenerative Disease. The chair of the department of neurology at that time had hired somebody named Dr. Andy Ahn. Andy worked on headache and pain, and the director needed a place for him. I had some space at that time, so Andy was a scientific neighbor, and we would have discussions.
The University of Florida is one of the hotbeds in the world in terms of a gene therapy approach based on adeno-associated viral vectors – we call it AAV for short. A former dean actually discovered this virus. One of our senior faculty members participated in creating the first gene therapy vectors around it. My lab had already been using AAV vectors, but we doubled or tripled down when we came to the University of Florida. AAV has a naturally affinity to get into neurons.
So Andy sort of triggered this, but my bandwidth was stretched at that point – it’s still stretched. I kept on tweaking Andy to go down this road. Andy left academics, and at some point I said I should do this.
We felt it could be something that could be rapidly translatable. Finding a cure for trigeminal neuralgia is a huge unmet medical need, but it’s an orphan disease that doesn’t affect enough people to attract a huge amount of attention.
There’s a chance for harm if we get into humans, but the nice thing about working with trigeminal neuralgia is we can at least start our initial studies in humans in people whose next option is surgical ablation of the trigeminal nerve. That means that there’s an out if we actually happen to make people worse. When we do these kinds of trailblazing experiments or envision them in humans, we need to make sure that if something could go wrong we have a way out.
Now we’ll begin the animal phase of study – testing in animals. And I know how much this research can really affect people’s lives. It may not work, but we have everything in place to test it. So let’s try.
If Gene Therapy isn’t new, why do you believe that it can work to block pain signaling in the nerve?
TG: It really comes down to technical details. People have used the wrong vectors before that had their own liabilities. I honestly just don’t think people have thought that much about this approach.
Last year, gene therapy had its first really radical major success outside of the eye, which was with children who had a disease called spinal muscular atrophy (SMA). They were treated systemically with a AAV vector – a different flavor of the same thing. These kids basically get spinal motor neuron degeneration when they’re young, by the time they’re two years old, typically, they die. Fifteen children were treated with huge amounts of virus, and reports last October showed that every one of these kids was alive at two years of age. And those with high-dose vectors, many of them were almost asymptomatic. At that age the expected survival rate would have been eight percent. So there are some children walking and living normal lives after gene therapy who otherwise would be most likely dead.
So I think that was a turning point in the field, to say this, AAV-based gene therapies, really will have its place in modern medicine. And that study in SMA was much more heroic and much more challenging than what we envision. So I think the time’s right. We know we can deliver the gene to the nerve. So now it’s just finding the right gene that will dampen pain signaling in that set of neurons, hopefully without doing harm.
Facial Pain Research Foundation
2017 Research Progress
Submitted
April, 2018
By
Douglas K. Anderson, Ph.D.
Eminent Scholar Professor and Chair Emeritus
Department of Neuroscience
University of Florida College of Medicine
and
Director of Research and Trustee
Facial Pain Research Foundation
Trigeminal Neuralgia (TN), is a prime example of neuropathic pain which is pain caused by injury to or malfunctioning of the nervous system. TN is considered to be one of the most painful afflictions known to humans with debilitating effects on the activities of daily living of individuals with this painful condition. The cost neuropathic conditions like TN adds to the U.S. health care system is greater than $100 billion/year yet funding for research from federal agencies, primarily the National Institutes of Health (NIH) and pharmaceutical companies continues to be woefully inadequate. The meagerness of funding from traditional sources has led the growing realization that discovering the root cause of and treatment for TN and other neuropathic pain conditions is going to have to be accomplished with funding from the private sector. To this end, The Facial Pain Research Foundation (FPRF) was created in January, 2011 to provide the critical elements that are necessary and sufficient to study these facial pain conditions. Consequently, the sole mission of the FPRF is “…to establish a well-funded translational (i.e., fundamental discovery to clinical application) research continuum that is dedicated to identifying the mechanisms underlying neuropathic facial pain and to develop novel new therapeutic strategies that will permanently stop the pain of TN and related neuropathic pain syndromes”. Since its inception a little over six years ago, the FPRF has raised over $4 million dollars to support six separate and distinct research projects. The FPRF uses three fundamental criteria in choosing which proposals are to be considered for funding: (1) the projects are novel and unique; (2) the investigator(s) responsible for each project are among the leading researchers in their respective fields; and (3) all of the projects are not “cut from the same cloth”, i.e., there is significant diversification in the research strategies among the projects. It is important to note that these FPRF funds have also served in a multiplier capacity in that some of our investigators have used FPRF support as seed funding to generate the necessary preliminary data which contributed to these investigators acquiring large grants from the NIH and other foundations and, in some cases, the acquisition of venture capital. Total dollars from these other sources that came to our consortium of investigators emanating, all or in part, from FPRF seed funds, is estimated to be somewhere over $30,000,000. The purpose of this yearly update is to briefly summarize these six projects and to highlight the progress that each achieved in 2017.
“Investigating Protein-Lipid Interactions in Peripheral Nerve Myelin”
Lucia Notterpek, Ph.D. (Principal Investigator)
Professor and Chair Department of Neuroscience University of Florida College of Medicine
Progress report (Year 3): May 2017-April 2018
Project 1: Cholesterol homeostasis in peripheral nerve myelin
Study staff: Ye Zhou, MS, graduate student
With Ye Zhou, a graduate student in Dr. Notterpek’s laboratory leading the way this group continued to make excellent progress on this project during the past year. They gave presentations based on the results at several meetings. Also they have submitted a manuscript titled “Peripheral myelin protein 22 is necessary for ABCA1-mediated cholesterol efflux’’ to PNAS Plus. However this article as written was not accepted for publication. Consequently they are in the process of adding an additional data set to this manuscript and shortly will submit the revised paper to an alternative high impact journal.
Recent publications in the literature along with data from Dr. Notterpek’s lab continue to indicate that cholesterol homeostasis is critical for myelin stability in both the central (CNS) and peripheral (PNS) nervous systems. They are focusing on mechanisms that involve cholesterol trafficking within the cells and cholesterol efflux from myelin-forming cells, including the potential exchange of cholesterol between the nerve and Schwann cells. Their studies indicate that the concentration and localization of cholesterol is tightly regulated within myelin forming cells, as in the absence of proteins that are involved in this process, both mice and humans develop neuropathies. They are also working on understanding how the correct amount of cholesterol is maintained in the myelin membrane, which is critical for membrane stability. Peripheral myelin protein 22 (PMP22), whose haploin sufficiency is linked with a compression induced neuropathy (that often is painful), is critical and necessary for assuring cholesterol transport to the membrane. Utilizing neuropathic mice with PMP22 deletion and point mutation, they discovered that PMP22 regulates cholesterol homeostasis and trafficking via the interplay with ABCA1, the major cholesterol efflux transporter. Considering the positive effects of drugs that facilitate cholesterol transport such as 2-hydroxypropyl-β-cyclodextrin (HβCD) in CNS myelination, along with the likely interaction between PMP22 and cholesterol (see below), they treated nerve explants from PMP22-deficient neuropathic mice with HβCD and found improvements in the myelination capacity of the affected cells in response to drug treatment, as compared to untreated samples. These studies will need to be repeated, but are leading us them toward potential therapeutic approaches on how abnormal levels of cholesterol in myelin could be corrected.
In another set of cellular/molecular studies, they have now identified the exact amino acid motif in PMP22 that likely binds cholesterol and are in the process of finalizing this study for publication. Related to this aspect of the project, Dr. Notterpek is in discussion with a membrane biophysicist at Vanderbilt University who has an assay to monitor the incorporation of normal and cholesterol-binding mutated PMP22 into lipid micelles and are working toward coordinating and/or combining their findings with his for publication purposes. Working with another University of Florida scientist, Dr. Habibeh Khosbouei, they discovered that critical properties of the glial membrane, such as membrane resistance and capacitance, change when the levels of cholesterol are abnormal, e.g., as occurs when PMP22 is deficient. To the best of their knowledge, no one else has performed similar single cell electrophysiological recordings of Schwann cells causing great excitement in the lab because understanding how abnormal membrane-associated cholesterol levels alter the ability of myelin to protect the axon and guide membrane depolarization (neuronal activity), are critical and fundamental aspects of neurobiology. Moreover, Dr. Notterpek’s group is continuing their investigation of the impact of dietary cholesterol on peripheral myelin health using mice with different genetic backgrounds, and discovering strong impact of genotype and gender on the response of the animals to a high fat diet. These studies are at various stages of sample and data analysis which when completed will serve as the foundation for future grant applications to the NIH.
Editors Note: Hanna Smith is a contributing writer for the Facial Pain Research Foundation. She is an award-winning journalist and assistant author of an in-progress medical biography detailing life with chronic pain. A student of bioclinical science, Smith studies surgical technology, psychology, physiology, and neurobiology to specialize in the medical treatment of individuals with disorders such as Trigeminal Neuralgia. Her father, diagnosed with Type-I TN for 26 years, inspired her to be dedicated to and engaged in the awareness, research, and medical practices that change the lives of people with chronic pain.
Shelly Forster:
The Purpose of Pain
Shelly with her family
By Hanna Smith
It was Shelly Forster’s most burning question: What is my purpose?
Fighting through reconciling the logistics of her new life diagnosed with chronic pain, rock bottom became her home in 2008 – and it left her with a choice.
2008 is the year Forster underwent two brain surgeries and was diagnosed with three chronic pain disorders – oral mandibular dystonia, trigeminal neuralgia and tardive dyskinesia – all of which transformed her from an independent woman working in nuclear engineering to a homebound patient fighting for her life.
“Pain is the great debilitator,” Forster said. “Chronic pain is a different animal all together, but takes on a new, terrifying element when it’s neurological.”
A congenital tumor inside Forster’s cerebellum was the root of her startling symptoms – muscular contractions in her neck, loss of voluntary control of her jaw and tongue, and splitting migraines.
For some time prior, Forster attributed the consistent headache and preliminary symptoms to stress at her job as a document control specialist for a nuclear engineering company. Such a job often required 70-hour weeks with round-the-clock hours. Forster assumed her symptoms to be somewhat normal considering the abnormal circumstances.
However, when the pain worsened and ultra-abnormal symptoms arose, she sought medical attention. Forster walked out of the doctor’s office with an emergency brain surgery scheduled the next day to remove the tumor inside around her cerebellum – the brain’s motor control center, which explained the involuntary movements in the cervical region of her head.
Dystonia impacts approximately 250,000 people in the United States, according to the American Association of Neurological Surgeons. Despite it being the third most common movement disorder, it is widely un-recognized by the public.
Forster underwent a surgery which removed the tumor. She was able to go home and began the recovery process. However, during a follow-up appointment, an additional MRI revealed there was a secondary tumor – this time woven within her cerebellum.
Forster for the second time was scheduled for emergency surgery, during which the surgeon filleted her cerebellum to remove as much of the tumor as possible. By the time the surgery was finished, however, 20 percent of the tumor was untouchable and too entangled in nerves. This portion still remains in Forster’s cerebellum to this day.
Prior to the operations, Forster says she understood her painful symptoms were in direct correlation with the tumors. Thus, following the surgical removal, she also assumed, based on medical opinion, that those symptoms would disappear.
Brent Maher, six time Grammy Award winner
speaks out about helping raise money for research
Letter from Tina
Have you ever stumbled across something so great and rewarding that you just can’t get enough of it? I did, and my life hasn’t been the same. And I am more than okay with that.
Living with chronic pain is challenging. It can be a struggle. A daily, grind it out, beg for it to be over kind of a struggle. Sometimes I can’t do the things I used to do be able to do, or the things that made me, me. But I also remember how much worse I felt and how destructive the pain was I experienced before I had microvascular decompression (MVD) surgery. I still hurt daily but knowing how much worse the pain of Trigeminal Neuralgia can be, I “face” my pain and my life differently now. A few months after my surgery, I decided one day I did not want TN to control me and push me back down into those dark depths of despair, isolation, and depression.
So I did what the millennials do these days.. I turned to the internet. One day while I was doing some research while volunteering for the Facial Pain Research Foundation (FPRF), I was looking into the ways people get TN- especially from head trauma. That search lead me down a path that covered our military and the way some of our wounded warriors have gotten TN from traumatic brain injuries. That got me thinking. If we are losing some of our veterans to this terrible beast called PTSD.. and some of them also have ‘The Suicide Disease’, that’s unimaginably not fair!
I immediately thought, how can I reach them?? How can I let them know about the FPRF and the research and work that is being done to stop this pain? How can I get to them to remind them to Hold On Pain Ends? If they don’t know about the Foundation, then they don’t know there is light at the end of the tunnel.. that scientists and researchers are actively working to stop the pain of TN and just maybe that will also help with some of their PTSD stressors.
First Published May 18, 2011
SIX TIME GRAMMY AWARD WINNER
TO PARTNER WITH OUR RESEARCH
FOUNDATION!
Brent Maher and Moraine Music Group of Nashville, TN have volunteered to become
Corporate Partners with The Facial Pain Research Foundation to find a cure for
trigeminal neuralgia and related neuropathic pain.
Maher says “I feel lucky to create music...and I feel blessed to have worked with
many great songwriters and performers but mIllions of people arenʼt so lucky...
They have tormenting pain that is depressing, agonizing and life taking...We at
Moraine Music are going to do everything we can to help the Foundation to find a
cure. We are committed.
Brent and Dianna Maher, Moraineʼs President, are working with Michael Pasternak and
the Foundation to plan fundraising activities to support our research. They will include a
number of songwriter and performer events and benefits. They are also involved in
creating public service announcements and other Foundation awareness materials and
videos. A video has already been “shot” of Brent and Michael in the Moraine studio and
is being edited for viewing on this webnewspaper.
Moraineʼs publication library includes over 10,000 selections. Eventually, you will be
able to purchase and download their hits on this webnewspaper with the proceeds
going to support our research to find a cure.
Visit Moraine at http://www.morainemusic.com/ and you will be able
to hear the music and learn more about Brent and some of the songwriters and
performers.
They are very excited about their commitment to finding a cure...and so are we!!
THANK YOU PAT AND AMY TOMASULO
AND CHICAGO
LAUGH YOUR FACE OFF Has RAISED OVER $1,200,000!!!
By Kris Gaganidze
The Fourth Annual LAUGH YOUR FACE OFF was held May 8, 2018 in Chicago’s beautiful neighborhood of Lincoln Park at the Park West. This marks a new date and a new bigger venue! All of this helped to make this year’s LAUGH YOUR FACE OFF a huge success. With temperatures in the high 70’s and a beautiful sunshine day to come out and help support The Facial Pain Research Foundation (FPRF) in their fight to find a cure for Trigeminal Neuralgia (TN).
To date LAUGH YOUR FACE OFF has raised over 1.2 million dollars for research for a cure for the rare nerve disorder called Trigeminal Neuralgia. The Foundation is currently funding six different research programs to find a cure for Trigeminal Neuralgia. TN is known to be one of the most painful conditions known to humans. It is often called the suicide disease because there is no known cause and no cure.
My husband, Kyr and I had the great pleasure of meeting Michael Pasternak six years ago. He is one of the people who started the Foundation looking for a cure. We got involved with Pat and Amy Tomasulo four years ago when we were asked to help with LYFO. What an honor to get to work with and know these amazing people. They are the brains and Founders of the brilliant LAUGH YOUR FACE OFF! This year’s LAUGH YOUR FACE OFF took place at the Park West Chicago. The venue was twice the size that we’ve had in the past. So over twice the number of people (700) attended Saturday’s event. The evening started with cocktails, appetizers, silent auction and raffle!
My husband and I had the privilege of checking in VIP guests, sponsors and TN patients. What a joy to thank our sponsors personally and give hugs to TN patients as they entered the event.There was a separate raffle set up just for the TN patients. I think they appreciated the thoughtfulness of a special raffle just for them! And a huge shout out to all of the returning and new sponsors! We appreciate your generosity and support!
The evening started with the very funny Pat Tomasulo warming up the audience with his great standup comedy. After Pat got the crowd laughing we never stopped. He was followed by five, yes five great standup comics. Thank you to Rocky Laporte, Brian Smith, Jeannie Doogan, Drew Frees and Mike Stanley.