THE DYSFERLINOPATHY JOURNEY
THE DYSFERLINOPATHY JOURNEY
I was diagnosed with Miyoshi Myopathy in 1988 shortly after I graduated from college. It took quite some time, however, to get a diagnosis back then. Until the DYSF gene and resulting dysferlin protein were discovered in 1998, the diagnosis was based on clinical observations, painful electromyograms and the physical appearance of muscle tissue under a microscope. Because such criteria can vary greatly among patients, there was some uncertainty as to whether my diagnosis was conclusive.
In hindsight, my symptoms started as early as the summer of 1981, when I noticed that I could not use the stomach crunching machine at the local gym. In 1983, I noticed that sitting straight up in a chair for extended periods of time had become uncomfortable, and I was not able to pass the physical training requirements as a Midshipman in the Naval Reserve Officer Training Corps. In denial as a young man, I chalked these problems up to needing more exercise.
Within a few years, however, I noticed symptoms that were difficult to ignore. By 1986, I could not keep up with my classmates while running, and I slipped very easily on ice that did not present a challenge to others. By 1987, I noticed that I struggled to stand on my tiptoes and found it difficult and exhausting to run and ice skate. I also noticed for the first time that the muscles on the back of my lower legs appeared flat. I then realized with some horror that additional exercise would not help and I sought medical attention.
Initially, I saw a podiatrist, hoping that I only needed inserts in my shoes to better exercise my leg muscles, but the podiatrist turned pale as a ghost when he saw my legs and referred me to a neurologist. That neurologist suspected I had Polymyositis or Charcot-Marie-Tooth disease, common misdiagnoses for this condition. Fortunately, he referred me to a neuromuscular specialist who diagnosed me as having Miyoshi Myopathy. Again, though, because there was no known genetic link at the time, the diagnosis was based solely on symptoms.
Since the initial diagnosis, I have been involved in a number of experimental treatments and clinical trials. In 1989, I took prednisone, and two years later methylprednisolone, in each case based on evidence that they increased strength in patients with Duchene Muscular Dystrophy (DMD). Neither made me feel any stronger and both made me feel exhausted.
In 1998, the DYSF gene and resulting protein were discovered, and by 2000 my doctor had identified the types of mutations on each of my genes. Soon after that, in 2001, I participated in a clinical trial of the antibiotic Gentamicin, which had been shown in animal models to read through a certain type of gene mutation. The hope was that Gentamicin would read through the premature stop in one of my genes and cause that gene to produce full length dysferlin proteins. It did not work as hoped, but the overall mechanism of action is promising and other compounds are in development.
In 2006, I participated in a clinical trial of an antibody called MYO-029, which inhibits the activity of myostatin, a growth factor that down-regulates muscle production. The theory was that by soaking up this enzyme, MYO-029 would cause increased muscle growth. I did not benefit from that trial, nor did the other patients, but there is still hope that myostatin inhibitors may work and further development continues.
My message to people who may have this condition is threefold: (1) See a neuromuscular specialist who is familiar with dysferlin deficiency, (2) contact the Jain Foundation for more information, and (3) get a genetic analysis! Sadly, there are still neurologists misdiagnosing dysferlinopathy patients with disorders such as Polymyositis or Charcot-Marie-Tooth, and who continue to dose dysferlinopathy patients with unhelpful, and potentially harmful, steroids. Fortunately, you can now be tested both for the presence or absence of the dysferlin protein and for mutations in the dysferlin gene. Not only is that hugely important to avoid misdiagnoses, but it will also facilitate your ability to be treated because different therapeutic approaches may work for certain types of mutations and not others. Getting a mutational analysis will also help others because the more patients who are definitively confirmed as having the disease, the more likely we will all get into clinical trials that will lead to a cure.
Finally, keep a positive outlook. I am very happy at age 45. Though the weakness progresses, I am otherwise healthy, and I am happily married and a successful partner at a law firm. This disease is a nuisance, but it need not be debilitating. Keep you chin up, contact the Jain Foundation to find out more about your condition and current developments in research and drug development and, once again, get that mutational analysis ASAP!