Growing up, Lisa Dilworth knew her family was different from others. She first realized the seriousness of her mom’s illness when her mom was hospitalized and wasn’t able to be home for Christmas. Her grandmother moved in and helped take care of her and her siblings, then 3, 4 and 5.
“My mom never scared us but never sugar-coated it either,” says Lisa. “Her disease never once made me angry; it just made me want to learn more and to do something about it.”
Lisa Dilworth will be speaking at DIA 2017 in Chicago on June 20 at 2 p.m. on Integrating the Patient's Voice Across the Development Program of Rare Diseases: Translation Into Meaningful Outcomes.
Lisa’s mom, Linda Hied, has Myasthenia Gravis, or MG, a chronic, autoimmune disorder that affects voluntary muscles. MG is often referred to as the “rag doll illness” because it causes patients to have muscle weakness. The body’s immune system attacks itself and weakens the muscles that help control the eyes, face, throat, limbs, and even the muscles which help us breathe. Without treatment it can be life-threatening. For Linda, the disease meant that it often prevented her mother to participate in family activities like bike rides and hikes. But Lisa says that never discouraged her mom.
“She encouraged us to do things like this and when we returned from an activity she was always right there with snacks, a smile, a warm hug and anxious to hear about our adventures even if that meant we had to climb into her hospital bed to do it,” she says. “This was our normal, and eventually you forget that other kids don’t have the same experience.”
Lisa says her family has always been close – not because of her mom’s disease, but in spite of it.
“We very much choose not to give the disease that much power,” she says. “We think it’s very important to acknowledge that a disease is just something you have, not something that you are.”
Watching her mom battle MG has always been a source of inspiration. Despite the surgeries, wheel chairs, countless hospital visits and myasthenic crises her mom never complains and stays focused on a better future.
“I admire my mom more than anything,” Lisa says. “She is a fighter. I admire her strength, her courage, grace, and her commitment to finding a treatment. My mom has never shown any signs of fear or defeat in her battle. She loves to talk to other MG patients and listen to their stories and share her experiences in hopes of comforting them. She also continues to try new off-label treatments or enroll in clinical trials.”
It probably comes as no surprise that Linda inspired her daughter to do what she does today—work on clinical trials. Lisa is Director of Therapeutic Expertise, Rare Diseases at PRA Health Sciences.
“It’s the only reason I went into this job. I was originally planning on going to medical school to be a neurologist because I wanted to treat patients like my mom,” says Lisa. “I saw the impact physician bedside manner had on my mom and I wanted to be one of the ‘good doctors’ who listened and cared because those few physicians she had who listened and cared about every single symptom she experienced made the biggest impact. But then, when I started working for my mom’s physician while an undergrad, I realized that the research was critical. I wanted to be a part of that. I witnessed first-hand how much hope patients found through participating in clinical trials. It was the perfect match for me.”
Lisa interviewed her mom about her experience as an MG patient and her hopes for the future of MG research.
Lisa: Can you briefly describe your journey from when symptoms first began to getting the diagnosis?
Linda: It was long, tedious and terrifying! I had complained of fatigue and weakness, constant bouts of bronchitis, inability to clear my lungs, excessive mucous production that I was unable to clear, certain foods were difficult to eat, speech was hard and as a teacher -- it was impacting my work. I had three pregnancies in four years so fatigue was to be expected. One doctor blamed it on me being a working pregnant mother and “screaming” at my students all day which I found very insulting. So I went to another doctor who told me I had Rheumatoid Arthritis of the throat and Chronic Fatigue Syndrome.
Next I was tested for MS and when that came back negative they diagnosed me with ALS. I found another physician who told me it was either ALS or Myasthenia Gravis (MG) and that I would need to be hospitalized briefly for a confirmatory test. That’s when they gave me the Tensilon test and I was diagnosed with MG. When they administer the Tensilon, all of your symptoms disappear. You are strong, your speech is normal, you can swallow etc. And I thought to myself “Ok, I have MG but all I need is this Tensilon and I’ll be cured.” My doctor has since educated me on why Tensilon can only be used to diagnose MG and not to treat it. [Here is more information on the Tensilon test.] I always found it to be a cruel diagnostic method! I would estimate the entire process took about six years from first seeing a doctor to proper diagnosis.
Lisa: What areas in your life have been affected the most due to Myasthenia Gravis?
Linda: The hardest part is that it has limited my activity with my three children and five grandchildren. In my early thirties, I needed help just to take care of my own kids because I wasn’t strong enough to pick them up some days. It also impacted my career. My MG was so bad that I was unable to speak and therefore unable to be a teacher. I lost my job at what should have been the height of my career and was unable to work again.
Lisa: What does a good day look like for you in terms of your illness?
Linda: It’s the little things that matter to me. If I have enough strength to take care of myself, play with my grandkids, or have lunch with my daughters then I consider it a good day. An ideal day would be a day where I don’t struggle breathing, don’t choke on my meals, have strong legs and can walk independently, and my voice is strong enough to communicate with people.
Lisa: How satisfied are you with your current treatment options?
Linda: I’m grateful for the neurologists who have treated me over all the years and the various treatments we’ve explored. But I do hope for a disease-modifying treatment. Right now we just try to deal with the symptoms of MG. But the side effects of life-long prednisone use and immunosuppression frighten me very much. The cost of my current treatment options is also a major hurdle as my treatments are primarily off-label and therefore not covered by insurance. I also hope for a treatment that can be administered at home. Plasmapheresis, IvIG and Off-label Rituxan all require that I sit in infusion centers for hours.
Lisa: Have you ever participated in a clinical trial?
Linda: Yes, I’ve participated in two clinical trials.
Lisa: What are your thoughts about clinical trial participation?
Linda: I think clinical trials are very important. And I think your physician plays a large role in your interest and awareness of clinical trials. The Informed Consent process is very long and frightening. I think my last informed consent document was over 15 pages long! But once you get through the first visit it is much more manageable. It is also terrifying waiting to hear if you are truly eligible for the study after that first visit. I find that waiting to be as emotionally challenging as seeking a proper diagnosis. You know there is an exciting trial out there and you just hope you will be allowed to participate.
Lisa: How much did your relationship with your physician play a role in your decision to participate in a clinical trial?
Linda: I would say it was one of the main reasons I decided to enroll in the clinical trial. I had been seeing my physician for 20 years, my daughter was working for him, and he was a family friend. I trusted his recommendation entirely. He was also very active in clinical research and he educated all of his patients on the importance of clinical research during support groups and other events he hosted. It was important for me to understand why clinical trials were needed and what a difference I could make if I enrolled. He has since retired and I’ve had to find a new neurologist.
Lisa: And now that you have a new neurologist, has that impacted your feelings toward clinical trials?
Linda: I would still be open to clinical trials but my current neurologist is not active in research so I would have to find a new neurologist. I do see MG clinical trials on Facebook from time to time but I’m not eligible because I have an ultra-rare version of MG where I have a unique antibody. Patients with my antibody (MuSK positive patients) are usually excluded from clinical trials.
Lisa: As a patient, what are your hopes for clinical trials?
Linda: I optimistically hope for a vaccine to prevent Myasthenia Gravis in the future and a cure for those who have it!
Lisa: What changes do you think would improve the clinical trial experience?
Linda: I think setting honest and realistic expectations from the time of consent would improve the entire experience. For example, other patients have told me that they found clinical trial information to be misleading. These patients thought that they would be cured through the clinical trial. If a drug seeks to improve certain symptoms of my disease but not provide a cure that should be made very clear. I would still participate in the trial because small changes are very important to me!
Lisa: What advice would you give to someone considering participation in a clinical trial?
Linda: Talk to people! It’s very important that you understand the clinical trial process, level of commitment, aims of the trial etc. Advocacy groups and online support groups are very helpful. For me, I found MG Friends to be a fantastic resource where I was able to connect with other MG patients and hear their clinical trial stories. It’s also important to understand if it will require involvement from your family. For instance, if you are going to need somebody to take you to doctor appointments because you can’t drive yourself then you need to make sure that you have somebody able to do this. You don’t just enroll yourself in the trial, you enroll your whole family and it will impact them.
Lisa: What comes to mind when you hear the term “patient-centric” clinical trials?
Linda: A truly patient-centric clinical trial would be one where I get to have a say in what the ideal outcome looks like. While I understand that a physician only thinks the drug works if it makes me stronger on the days he/she sees me in clinic, for me, a drug works and is valuable if it just means I can babysit my grandkids one day a week. If I’m strong enough to do that, it’s good enough for me. But that isn’t something that is going to show up on a blood test or in a physical exam at the clinic.
Lisa: How has having a rare disease empowered you in other areas of your life?
Linda: That’s a tough question, I’ve never thought about it because I don’t think my disease defines me. In fact, each day I aim to minimize the impact MG has on me and my family. I guess in that regard you can say it has made me defiant. I refuse to hand over my power to this disease.
Facts about Myasthenia Gravis
In MG, the body produces antibodies that most commonly target acetylcholine (AchR) receptors on the surface of the muscle cell. These antibodies block the receptor where signal to contract should be received and also activate the complement pathway which causes muscle cell destruction. Additional antibodies are found in MG such as antibodies to muscle-specific receptor tyrosine kinase (MuSK).
What are the symptoms?
Common symptoms can include drooping eyelids, blurred and double vision, slurred speech, difficulty swallowing, chronically fatigued muscles, limb weakness and difficulty breathing.
Who gets MG?
MG is considered a rare disease. It is estimated to impact about 14-20 out of 100,000 individuals in the US although it is likely under-diagnosed. MG does not spare any gender, race, or age. While the underlying cause of MG is still not understood, it occasionally occurs in more than one member of a family.
How is MG currently treated?
Before treatment was available, 70% of MG patients died, mostly due to pulmonary complications. Now, with treatment, the mortality rate of MG has been reduced. However, most medications have not been studied in controlled clinical trials of Myasthenia Gravis patients and therefore the use of many of these drugs is off-label.
Current treatment for MG aims to manage symptoms and avoid the likelihood of a myasthenic crisis, a life-threatening manifestation of the disease.
- Acetylcholinesterase Inhibitors: help to increase the amount of acetylcholine at the neuromuscular junction and prolong the effects of Ach.
- Thymectomy: Surgical removal of the thymus seems to reduce muscle weakness
- Corticosteroids: frequently prescribed to improve symptoms but not without side effects
- Intravenous Immune Globulin: aims to impact the function and production of antibodies in the immune system
- Plasmapheresis: Short-term intervention on the verge of crisis involving the selective removal of the patient’s plasma which is then replaced by special intravenous fluids.
- Immunosuppresives: used to reduce the production of autoantibodies
What does the future hold for MG patients?
The Myasthenia Gravis community is committed to finding a cure for this debilitating disease. Through clinical trials there is hope of better understanding the disease and hope for a cure.
Possible new agents with a variety of mechanisms of action are currently planned for clinical trials. Some approaches include an aim to target the complement pathway, a subcutaneous route of immunoglobulin, monoclonal antibodies, and a therapeutic vaccine. There is also a MG registry study currently open.