Insider’s View

Daniel Drachman, M.D.

Daniel Drachman, M.D., is a longtime Hopkins neurologist / researcher who specializes in neuromuscular diseases.

Is ALS One Disease?
Although the features of ALS we see in the clinic are similar from patient to patient, convincing evidence now exists that ALS is not “one disease” with a single cause. Rather, it’s a clinical syndrome—a cluster of symptoms—that results in destroyed motor nerves and eventual paralysis.

Impressive advances are making it clear that any number of things may trigger a cascade of processes that leads to the death of motor nerve cells. The factor that correlates most closely with ALS is increasing age. In fact, the inherent vulnerability of motor nerve cells becomes greater with age and surely plays an important role in the disease. Other factors, however, are also important. For example, 1 percent to 2 percent of all ALS patients have a heritable mutation in the gene for an enzyme, superoxide dismutase. Yet the inherited forms of ALS are indistinguishable from the spontaneous disease most patients have.

Still other events—as varied as electric shock, trauma to limbs or to the spinal cord, or even eating nuts from cycad trees in Guam—are associated with onset of the disease. All this tells us that ALS cannot have a single cause and, accordingly, isn’t a single disease.

Research has uncovered specific processes that participate in the cascade that destroys motor nerve cells. They include excessive nerve stimulation and the resulting release of damaging substances such as free radicals or nitric oxide derivatives. Recently, Center scientists have shown that an inflammatory enzyme commonly called COX2 plays a key role in nerve-cell damage in ALS.

I like to visualize these events that surround ALS as a ball at the top of a staircase. If the threshold between the ball and the first step is high—when a person is young—the ball is unlikely to roll down. With increasing age, the threshold is lower. Many things can push a ball over a low threshold: a breeze, an accidental kick or an earthquake. Once the ball begins its descent, it falls inexorably from step to step, until it reaches the bottom. It is perhaps less crucial to try to discover all the events that may start the ball on its way than to learn how to slow or stop its fall. Similarly, ALS research is most profitably aimed at discovering the steps in the neuron-damaging cascade and finding how to interrupt them.

You can submit questions for the clinician by e-mailing the editor, mcentofanti@jhmi.edu.

Next > From the Clinic
Lora Clawson, M.S.N., C.R.N.P., manages Johns Hopkins’ ALS clinic. She also oversees its clinical trials. In this column she answers typical patients’ questions.