Robert J. Hopkin, MD, clinical geneticist, Cincinnati Children's Hospital Medical Center, speaks on the symptom burden and current therapeutic interventions available for Fabry disease.
There are several current options available for the treatment of Fabry disease, such as enzyme replacement therapy and pharmacological chaperones for some patients, but there remain no medications that can reverse the damage caused by the condition, said Robert J. Hopkin, MD, clinical geneticist, Cincinnati Children's Hospital Medical Center.
Can you discuss the current standard of care in Fabry disease?
Once somebody has a diagnosis of Fabry disease, there are a couple of current options. One of them is enzyme replacement therapy and that is typically given by IV [intravenous] infusion every 2 weeks.
There are 2 dosing regimens that are used in the United States, it's usually 1 milligram per kilogram in Europe and in several other parts of the world, there is one company that recommends 0.2 milligrams per kilogram every 2 weeks, and another company that recommends 1 milligram per kilogram.
That's really just replacing the enzyme that is missing and it is given by IV, taken up by the cells, and gets into most parts of the body. A lot of the enzyme is taken up in the kidneys and the heart, which are the main target organs that have life threatening complications associated with them. The enzyme is also distributed to other body parts.
Unfortunately, enzymes are large proteins, and they don't really get into the nervous system very well. So, some of the aspects of Fabry disease are not very well treated with that. In addition, some of the damage done by the time we're starting treatment is irreversible. So, there are some aspects of the disease that need to be treated with symptom-specific treatments.
For example, if somebody has proteinuria, we need to treat the storage disease and the proteinuria. And the proteinuria would be treated with separate kinds of medications. So, a lot of symptoms that go along with Fabry disease. The initial symptoms are often neuropathic pain, GI [gastrointestinal] symptoms, including abdominal pain, recurrent diarrhea, and sometimes nausea and vomiting.
Then, as the disease progresses, you'll see proteinuria with progressive renal damage, eventually leading to end stage kidney disease. And progressive heart disease that can start with bradycardia and then hypertrophic cardiomyopathy, sometimes rhythm disturbances, and eventually life threatening heart problems like heart failure or heart rhythm disturbances. So, we need to treat all of those things.
Now, in addition to the enzyme replacement therapy, for people who have the right mutations, there is an oral medication that functions as a chaperone. So, if your body makes some of the protein, then the chaperone molecule makes or helps to get the folding pattern of the protein into a physiologic form and maintains the stability so that the enzyme can be transported to the lysosome and function.
People who have mutations that are responsive to that can take an oral medication that, once taken every other day, basically optimizes your body's ability to make the enzyme. Both of those treatment options have been shown to be useful, and they do clearly benefit the patients, but they don't reverse damage that's already been done. And they don't directly impact all of the manifestations of Fabry disease as completely as we would like.