ALD - balancing hope against reality.

My wife Ann and I have been concerned with Adrenoleukodystrophy (ALD) since 1978 and now work on little else. The current situation with ALD is a perfect example of the hopes and controversies that arise when as yet unproved, still imperfect therapies emerge for a previously untreatable disorder.

The last 15 years have seen a number of exciting developments in diagnosis, prenatal screening and carrier detection. And recently, the ALD gene itself has been isolated. Wholeheartedly supporting our efforts has been a fine and extremely valuable parents' organization--the United Leukodystrophy Foundation (ULF)-- now in its twelfth year. Parents value all the advances that have been made, but in the absence of effective therapy, these advances are "fiat" and unsatisfactory.

In search of therapies

During our 12-year association with the ULF, we have come to realize that if we lose credibility with parents, we lose everything. We must always inform families of the facts, as we understand them at any given moment. The facts can be painful. Sometimes it is impossible to tell the truth to families without shattering their hopes and creating despair. To help reduce such despair and in a genuine effort to advance the capacity to treat, we offer all patients the chance to enroll in therapeutic protocols that have a rational basis and are free of inappropriate risk. These experimental treatments are monitored by an expert Institutional Review Board and have the full knowledge and endorsement of the ULF.

Our primary and increasingly passionate efforts are directed toward the search for an effective therapy for ALD. We are deeply concerned and frustrated that treatments are still so imperfect. Current hopes rest with dietary therapy, bone marrow transplantation and--in the more distant future--gene therapy. In addition, we are studying families in which some members are affected by the rapidly progressive form of the childhood disease, while their affected brothers, uncles or grandfathers have only the milder, adult form. Understanding the ways in which the rapidly progressive form of the illness develops may lead to the ability to alter these mechanisms.

Success of current therapies

Though "Lorenzo's Oil" was a good and highly rational idea, research has shown that it is of little or no benefit to patients who already have significant neurological problems by the time they start this therapy. However, our recent data suggest that "Lorenzo's Oil" may help to prevent the onset of neurological problems if it is started before such symptoms are present.

Bone marrow transplantation is a promising therapy for ALD--but only when performed early in the course of the illness using a well-matched marrow donor. Gene therapy is a great hope also, but its use is a number of years away.

The rapid progression of the most serious and common form of ALD-- the childhood cerebral form--is caused by a brain inflammatory response. At this moment, we do not have a therapy for this form of the disease. We are about to initiate an entirely new treatment, however. If successful, this therapy will work by suppressing the inflammatory response of the brain.

Hugo W. Moser, M.D., is Director of the Mental Retardation Research Center at the Kennedy Krieger Institute in Baltimore, Maryland, and Professor of Neurology and Pediatrics at the Johns Hopkins University School of Medicine.