The Alex and Jaci Hermstad Rare Disease Trailblazer Series - Her Stories: ALS

As an Emmy, Golden Globe, and Screen Actors Guild Award winner, Julianna Margulies has achieved success in television, theatre, and film. Margulies starred as Alicia Florrick on the long-running hit CBS show The Good Wife, which she also produced, and is also well known for her role as one of the original cast members of ER. More recently, Margulies has starred on critically acclaimed series including Billions and The Hot Zone and she will soon be seen on the sophomore season of Apple TV+'s The Morning Show. Julianna will add author to her list of credits this May with the release of her upcoming memoir, Sunshine Girl: An Unexpected Life. She has been involved with Project ALS and Erin's Law and is also a board member of the New York City-based MCC Theater company. She resides in New York City with her husband and son.

In early August of 2019, at age 27, I started to notice a slurring in my speech and a sluggishness in my tongue. I described it as a feeling of “marbles in my mouth.” Others around me, even my then-fiancé, Joe, said they didn’t notice any difference in my speech. But I was sure something was wrong. A neurologist I saw in fall of 2019 ordered an MRI. When it came back normal, she said not to worry and sent me on my way. By that time, I was also experiencing some stiffness in my left leg, and I had an unexplained fall in the house. But it wasn’t until Christmastime when a nurse friend, home for the holidays, told me I should get a second opinion. I went with my fiancé to a different neurologist on January 17, 2020, an appointment that changed my life forever. Now, almost two years after the onset of my symptoms, I have trouble walking long distances and rely on a walker outside the house. I can make myself understood when speaking, but I talk much more slowly and sometimes feel out of breath. I just completed a six month trial of an experimental drug (one of several) that researchers hope will be effective at slowing ALS’s symptoms, and am hoping to participate in another trial. While my story is similar to many others, I have had one constant that not all of my peers with ALS share. Ever since my diagnosis, I’ve received complete and unconditional support from a strong network of colleagues, family, and friends.

Dr. Crean is Executive Director, Clinical Development at Ionis Pharmaceuticals and leads the clinical development of Ionis’ antisense oligonucleotide therapy programs for several rare, neurological disorders. Dr. Crean has more than a decade of experience in clinical development across the spectrum of neurodevelopmental to neurodegenerative diseases. Prior to joining Ionis, Dr Crean was a senior researcher at The Scripps Research Institute, where she led translational research programs studying the impact of neurological disorders on brain functioning.

I have a long-standing interest in neuroscience that was fostered through a high school internship in Dr. Allan Basbaum’s lab at the University of California, San Francisco, where I focused on characterizing pain circuits in the spinal cord. I then pursued a major in neuroscience at Barnard College. For my undergraduate thesis work I studied the contributions of dopaminergic systems to behavioral timing in Dr. Peter Balsam’s lab and to schizophrenia in Dr. Stephen Rayport’s lab. I continued to study on the molecular underpinnings of schizophrenia as a graduate student in Dr. Sidney Strickland’s lab at Rockefeller, where I explored the effects of in vivo ablation of GluK4, a gene whose misexpression has been linked to schizophrenia and bipolar disorder in human patients. This project provided the opportunity to refine my skills in mouse genetics and behavioral phenotyping, which would later become critical to my work in ALS. Through my graduate work I also developed a strong interest in neurodegeneration. I discovered that GluK4 is critical to excitotoxicity and ischemic cell death in the hippocampus, and found that GluK4-mediated neurodegeneration is dependent on the activation of MAP kinases, which would reemerge as an important focus of my work in ALS as a postdoctoral research scientist with Drs. Hynek Wichterle and Chris Henderson at Columbia.

At Columbia, I honed my skills in human stem cell culture and validated new motor neuron differentiation protocols. I then optimized small molecule-based screening platforms to identify new therapeutic compounds to treat ALS. This work, performed in collaboration with Dr. Brent Stockwell, led to the discovery of prosetin, a novel MAP4 kinase (MAP4K) inhibitor that protects motor neurons from ER stress and slows behavioral deficits in mouse models of ALS. The MAP4K/CDK/GSK3B inhibitors kenpaullone and alsterpaullone also emerged as hits from these screens, and I performed the in vitro and in vivo characterization of novel, soluble paullone derivatives as they were synthesized in the Stockwell lab. This work led to the discovery of kleinerpaullone. I have also been instrumental in the development of new genetic screening platforms in cultured motor neurons to understand the complex regulatory networks that are engaged in the context of ER stress. These genetic screens have highlighted the importance of MAP4Ks, as well as CDKs and GSK3B to neurodegeneration in the context of ER stress.

In my current role as Director of Internal Operations at the Project ALS Therapeutics Core at Columbia University, I oversee the work of 5 technicians to design and coordinate in vitro and in vivo ALS drug screening efforts. I also coordinate collaborative projects between 8 Columbia PIs and have initiated ongoing scientific collaborations with multiple outside academic and industry partners.

Our family has a deep and multi-generational connection to ALS. Our mother succumbed to ALS in 1987. She was almost 33, leaving behind her husband & three children. In March 2020, at 38, Erin, her eldest daughter, was not only diagnosed with ALS, but also learned she carries the same FUS-ALS mutation carried by her mother, two aunts, & uncle.

Since her diagnosis with ALS at age 32, Gwen Petersen has poured her energy into advancing the science of her disease. Gwen has participated in more than thirty-five observational ALS studies, 10 of which are ongoing, as well as two interventional trials with an experimental therapy. Prior to her diagnosis, Gwen worked as a Recruiter for one of the top ten medical centers in the country. Accomplishments include:

• The New York Times, As M.L.B Honors Lou Gehrig, It Shines a Spotlight on A.L.S, published June 2, 2021
• CBS SF Bay Area (KPIX) news segment, A Dosage of Hope, aired August 10, 2021
• Selected as Patient Fellow (1 of 6 global selections) for 2019 ALS/MND International Symposium- world’s largest conference on ALS/MND
• Selected as Research Ambassador for 2018 Northeast Amyotrophic Lateral Sclerosis Consortium (NEALS), Clearwater Beach, FL, October 4-5, 2019
• CDMRP ALS Research Program, Consumer Reviewer, FY2020 & FY2021
• Patient Advisor to Pharma: Alector, Amylyx, Annexon, Apellis, Corcept, Cytokinetics, Denali, Healey Center ALS Platform Trial, Healey Center ALS Expanded Access Programs, Orion, Orphazyme, PatientsLikeMe, Project ALS, Sanofi, Seelos, Verge Genomics

Helen-Marie Dunmore is a principal scientific advisor who has significant experience with regulatory requirements in the nonclinical development of advanced therapy medicinal products (cell and gene therapies) and a wide range of large and small molecules.

Dr. Holly Kordasiewicz is Vice President of Neurology Research at Ionis Pharmaceuticals, a company that specializes in RNA therapeutics. Dr. Kordasiewicz leads a team focused on identifying antisense oligonucleotide therapeutics for currently untreatable neurological diseases, including drugs now in clinical trials for ALS, Alzheimer’s disease, and Parkinson’s disease.  Dr. Kordasiewicz joined Ionis 10 years ago after completing her post-doctoral fellowship in the laboratory of Dr. Don Cleveland at the University of California at San Diego where she worked to develop therapies for Huntington’s disease.  Dr. Kordasiewicz began her work on understanding neurological diseases at the University of Minnesota, where she received her Ph.D. in Neuroscience.

Jinsy A. Andrews, M.D., M.Sc., FAAN is an Associate Professor of Neurology, in the Division of Neuromuscular Medicine and serves as the Director of Neuromuscular Clinical Trials at Columbia University. She currently oversees neuromuscular clinical trials and cares for patients with neuromuscular disease, primarily with Amyotrophic Lateral Sclerosis (ALS). Dr. Andrews has extensive experience in all phases of human clinical trials and drug development in both the academic and industry settings. Dr. Andrews is the elected co-chair of the Northeastern ALS (NEALS) Consortium, which is a network of over 100 ALS clinical research centers internationally. She is also elected to the National Board of Trustees of the ALS Association and is a Fellow of the American Academy of Neurology (FAAN). Dr. Andrews has also received the Diamond Award for ALS clinical research from Wings Over Wall Street and the Muscular Dystrophy Association. Dr. Andrews received her B.S. from Union College, M.Sc. in Biostatistics (Patient-Oriented Research) from Columbia University's Mailman School of Public Health and M.D. from Albany Medical College. She completed her residency training in Neurology at the University of Connecticut and served as the Chief Neurology Resident in her final year. Dr. Andrews completed fellowship training in Neuromuscular Disease/ALS and Clinical Neurophysiology at Columbia University. She is board certified in Neurology, Neuromuscular Disease, and Electrodiagnostic Medicine.

My goal is to use every negative experience as an opportunity to see how to better help the system and to make accessibility the first thought rather than the second. In June of 2021, it will be 5 years since I was diagnosed with the death sentence that is ALS. Since most people with ALS pass away within 2 to 5 years of diagnosis this is yet another blessing amidst my daily miracles. Miraculously, I am still able to type, communicate, and work full time as a psychologist. It is a daily testament each time God helps me to move and to breathe. As I have become progressively more paralyzed, we have seen great strides in ALS research and I believe we will one day find a cure. Together we can continue to raise funds and provide tools to help others function to the best of their abilities until that cure arrives.

Kristina Bowyer joined Ionis in 1992 and currently serves as the Vice President of Patient Centric Drug Development. She founded Ionis’ Patient Advocacy program 2012 to ensure that the patient perspective is incorporated into every aspect of drug development from research through market authorization. Kristina’s expertise is in rare and neurological diseases where she has developed new strategies to capture burden of disease from both the patient and the caregiver perspectives through innovative partnerships across multiple programs and organizations, such as spinal muscular atrophy, amyloidosis, myotonic dystrophy and ALS. Ionis currently has an extensive rare disease pipeline of RNA targeted therapeutics and has established strategic alliances with global pharmaceutical companies with the expertise to successfully launch rare disease treatments and ensure broad patient access.

An ex-FDA reviewer, Lauren Black is now a Distinguished Scientist at Charles River with more than 25 years of experience in drug development, focusing on accelerated translation to Phase I/II clinical trials.

In December, about nine months after learning that I likely had ALS, I received a diagnosis to confirm the prognosis. The official diagnosis was primarily to facilitate paperwork. By then, I was beginning to feel my autonomy slip away. As Covid-19 began to force us indoors, ALS forced me to accept the use of a wheelchair. From home, I readily worked on proposals and discussed future plans with colleagues but, in the back of my head, knew that I would no longer be working by the time they came to fruition. Early summer, I took medical leave. ALS is a formidable deluge, progressively taking away independence and thrusting one far from their comfort zone. I have had to learn how to ask for help and how to accept it. How to live in the now and concentrate on those I’m with. How to rethink my definition of success and what I want from life. Today, I have moved back to the States to receive a novel treatment at Columbia Medical Center and be closer to family. I have married my fiercely loyal boyfriend of 6+ years. I have never felt more loved, more fortunate and more hopeful.

Lori Hermstad, 54, grew up in Storm Lake, Iowa, is a graduate of Buena Vista University with a Bachelors in Education. Today Lori resides in Spencer, Iowa, with her husband Jeff.

I had just turned 32, bought a house with my husband and was ready to start a family when I learned I had ALS after experiencing stiffness and weakness in my right hand and muscle twitching. Soon after my diagnosis, I jumped into advocacy to raise awareness and funds for research and new treatments for ALS. As an athlete, I have the spirit to fight and my background in communications helps me get the word out about ALS. Being a young woman with ALS introduces even more complexities to an already complex disease. I’m determined to keep living my life and accomplishing my dreams despite my diagnosis and help change the face of ALS for good. ALS has made me appreciate the simple things in life more and taught me how you react to your situation is everything. Not having effective treatments is frustrating, but I know that my positive outlook can have a powerful impact on my outcome. So I try to spend as much time enjoying every moment life brings as much as I’m fighting for better treatments for ALS. It’s all about balance!

I am a 41-year-old, single mom, diagnosed with ALS at 32. I had to retire in 2017 from my career as a Nurse Practitioner. Losing my independence and ability to work have been my hardest losses. Although I am no longer working, I maintain my license and continuing education because I love learning and being a resource for others. My aging parents and teenage daughter are my primary caregivers. Before diagnosis, I was a road warrior … school activities, swim practice, Girl Scouts, birthday parties … you name it. I was there!

I had about 3 “good” years after diagnosis before my progression became disabling. Today, I can no longer walk unassisted, have limited use of my arms and hands, and noticeable speech impairment.

Sabrina Paganoni, MD, PhD, is the Co-Director of the Neurological Research Institute at the Massachusetts General Hospital and Assistant Professor at Harvard Medical School. Her research focuses on clinical trials and therapy development for ALS. She has served as PI of several ALS clinical trials and has been using novel trial designs, novel endpoints and digital technology tools to innovate the way investigational products are tested in ALS. She is the co-PI of the HEALEY ALS Platform Trial, the first platform trial for ALS in the world. She recently reported the positive results of the CENTAUR trial and is the co-Chair of the upcoming global PHOENIX trial. Her research has been funded by the NIH, non- profits, and industry; she published more than 100 peer-reviewed manuscripts and received several awards for her work including the 2021 Top 10 Clinical Research Achievement Award for the CENTAUR trial.

I’m Sarah, a happily married dog mom from Austin, Texas. I love being active outdoors and used to be active in a competitive pool league! I was diagnosed with ALS at 39 and have been actively treating my underlying causes since.

Hey y’all I’m Sunny. I was diagnosed in January 2015 at 27, and just celebrated 6 years and my 34th birthday. I’m a dog and cat mom that lives in Hico, TX. I’ve traveled the world as an ambassador and advocate for those of us living with this disease. My advice to anyone regardless of disease affiliation or tenure is to lean into this community.

Barbara Killian is Associate Director of Discovery at Charles River. Her 30 years’ experience in drug development started with molecular biology research, eventually transitioning to product management. She joined Charles River in 2017 to manage in vitro Biology Assay Development. In addition, she oversees Charles River’s Rare Disease Portfolio aiming to connect researchers and the Rare Disease Community. Driving effective therapeutics and support to ALS patients is a passion for her as her father-in-law Richard, struggled with the disease for 9 years.

Erin Fleming is a research consultant for Project ALS, a non-profit 501(c)3 organization that identifies and funds promising scientific research toward the first effective treatments and a cure for ALS. Project ALS recruits the world’s best scientists and doctors to work together—rationally and aggressively—to develop a better understanding of the ALS disease process and, in parallel, better therapeutic strategies.

Previously, Erin was director of research operations at Project ALS, project manager at the biotech Applied Therapeutics, and project director at the boutique life sciences consulting firm Clearpoint Strategy Group. She holds a BA in English and Comparative Literature from Columbia University.

Valerie Estess is a co-founder of and director of research for Project ALS, a non-profit 501(c)3 whose mission is to find and fund promising ALS research toward effective treatments and a cure. Sisters Valerie, Jenifer, and Meredith Estess started Project ALS in 1998, when Jenifer, a thirty-five-year-old theater and film producer, was diagnosed with ALS. Over two decades, Project ALS and its world-leading research teams have contributed to meaningful breakthroughs in ALS genetics, motor neuron and stem cell biology, disease modeling, and drug screening. With Jenifer Estess, Valerie is co-author of Tales from the Bed: A Memoir. She lives in New York.