The director of the mitochondrial research program at Akron Children’s Hospital spoke about how to best manage a condition such as PMM, where there are no FDA-approved therapies.
Bruce H. Cohen, MD
Although there are a couple of chemicals in development for the treatment of primary mitochondrial myopathy (PMM), currently there are no FDA-approved therapies. Thus, physicians are left to manage the symptoms of the condition with what they can.
Over the years, the treatment paradigm has been regimens of vitamins and supplements. But little to no evidence exists showing the benefit for treating exercise intolerance, muscle wasting, fatigue, muscle cramps, and the like with these regimens. And while PMM is considered a rare disorder, estimates suggest 1 in 5000 people have the condition, adding to the imperativeness of getting therapy to market.
To better elucidate the treatment landscape for PMM, NeurologyLive spoke with Bruce H. Cohen, MD, the director of the mitochondrial research program at Akron Children’s Hospital, who has been involved in treating the condition as well as the clinical development for some of the potential treatments. Cohen, who is also a professor of pediatrics at Northeast Ohio Medical University and the director of the NeuroDevelopmental Science Center at Akron Children’s, spoke about the challenges of treating a condition like PMM.
Bruce H. Cohen, MD: For example, many of our patients have weakness, both chest wall weakness and neck weakness, that leads to sleep disorders like sleep apnea. One challenge is to get these patients’ sleep studies done and get them on proper sleep management therapy. Sometimes we get wrapped up in the details of the biology of mitochondrial dysfunction and can forget to always go back to the basics of patient care. One challenge is actually getting the sleep study performed Make sure your patient gets the sleep study, and when they’re diagnosed with sleep apnea, make sure they get the proper treatment for their disorder. That helps a lot. It really does. Sleep apnea treatment helps a lot in patients with myopathy.
For patients that need physical therapy, getting physical therapy to get the patient safely able to exercise to the extent they can exercise can be helpful. Some patients depend on orthotics and braces, so some patients benefit from that. Those are the types of symptom management I’m talking about. You’ve got to stay on top of that with your patient, and on their diet as well. Any diet that leads to excessive fat accumulation is going to make it more difficult for a patient to properly move around. And as we know, regardless of a mitochondrial diagnosis or not, proper nutrition is critical to a healthier life.
There are a number of review articles regarding how to screen for PMM. Many, but not all adults with PMM have ophthalmoplegia. With any patient with ophthalmoplegia, mitochondria myopathy ought to be in the differential diagnosis, and certainly, any patient with myopathy, exercise intolerance due to myopathy, fatigue due to myopathy, it ought to be a flag in the differential diagnosis. Then, any patient who has myopathy in with other organ system involvement, whether it be retina, optic nerves, sensory and neural hearing loss, deep neck myopathy, the hepatopathy included in something like nonalcoholic steatohepatitis, diabetes—those are the main comorbid disease states that go along with myopathy that can signify and underline primary underlying mitochondrial myopathy.
It probably occurs in about 1 in 5000 people. It’s not as common as Parkinson disease, but it’s certainly a lot more common than many other diseases many people know about. It’s not an ultra-rare disease, but it’s still considered a rare disease. I would also say there’s plenty of patients I run into that, in my experience, have been under the care of their physicians for the symptoms for many years before the diagnosis is made. It’s a lot easier to make the diagnosis now than it was 5 years ago because testing can really swiftly and inexpensively make the diagnosis. The decision to move forward with genetic testing is not without pitfalls and challenges and must be done with a proper understanding of what these tests prove and do not prove, as well as caveats in interpretation. In addition, proper informed consent must be performed and if the neurologist is not comfortable with this process, I recommend involving a geneticist or genetic counselor to help out.
Genetic testing is inexpensive compared to the previous method, which was the muscle biopsies. Muscle biopsies would run about, with all the bells and whistles, up to $40,000 including the pre-op evaluation, the cardiac evaluation, operating room time, anesthesia fee, the operating fee, the chemical analysis fee—that ran up to $40,000. And now, the price of a clinical exome is variable, but you can find companies that will do mitochondria DNA testing for about $1000 and a full exome for about a $1000, so you can get the whole package for under $2000. Although that’s not inexpensive, it’s comparable to what we pay for a brain MRI scan for a patient with headaches. The challenge is getting the insurance company to pay for genetic testing.
Transcript edited for clarity.