How a Postcard Makes a Point

he postcard from Disney World is an odd slide among the charts, tables and illustrations that neurologist Daniel Drachman, M.D., uses in presentations on myasthenia gravis. But Drachman, who leads Hopkins’ neuromuscular clinic, tells doctors-in-training the card from his longtime patient Linda Mondell is the ultimate litmus test. “When you get a patient with MG who can weather the exertions of Disney World, you know you’re doing something right.”

Since the 1970s, Drachman’s group has probed the root cause of the muscle weakness and fatigability that causes double vision, drooping eyelids and weakness in the limbs. The failure of muscles to respond to nerve impulses, they found, is caused by too few receptors for the neurotransmitter acetylcholine. These receptors then become the targets of an antibody-mediated autoimmune attack.

It was at her fifth high school reunion in 1962 that Mondell noticed her first symptom—slurred, nasal speech. Later her legs became so weak that while driving, she could barely lift her foot from accelerator to brake. A business trip with her husband in Hawaii was the last straw. “I couldn’t walk from the hotel to the beach. My legs kept buckling underneath me.”

When Mondell’s symptoms first appeared, the mortality rate for MG was around 30 percent. Another 30 percent of patients stayed the same or deteriorated, and only 30 percent improved. During the last 25 years, significant advances have illuminated the causes of MG, and now 90 percent of patients with this formerly “grave” disease can be restored to fully productive lives. “I’ve seen it happen hundreds of times right here in our clinic,” Drachman says. A host of immunosuppressive agents are the best treatment available, but these drugs must be skillfully used because they act in nonspecific ways and can produce side effects. Drachman is exploring more finely focused agents that will interfere selectively with the immune process.

In many cases, drug treatment is supplemented with removal of the thymus—helpful in up to 80 percent of cases—which likely plays a role in initiating the autoimmune response. Drachman, approaches thymectomy with caution. “It should never be performed as an emergency procedure,” he warns. “It requires special pre- and post-operative management.”

Using new immunosuppressive drugs in innovative combinations, Drachman’s group is curbing even the most difficult MG cases. For the rare patients who don’t respond adequately to these conventional treatments, a trial of “re-booting the immune system” is under way. And new experimental strategies that use a person’s own immune system to target and turn off the abnormal response—a kind of immunological jujitsu—are showing exciting promise in laboratory models.

Mondell’s treatments have brought her myasthenia under control. “The kicker in all this is that myasthenia is the best understood autoimmune disease in neurology,” Drachman says. “Whatever strategies we’re able to develop will be applicable to other autoimmune diseases.”

-- ABS