In late 1996, Nymox Pharmaceutical Corp., a little-known Montreal drug company, ran an ad in TV Guide for a new diagnostic test for Alzheimer's disease. "Alzheimer's--Now you can rule it out," the copy said. It offered the promise of relief to worried patients and their families. The only problem, some scientists say, was that the ad was misleading. The test was unproven, they say, and the company's claim that it could "rule out" the dread ailment was unsupported by published data or scientific consensus.
The Nymox test detects elevated levels of neuronal thread protein (NTP), a substance linked to Alzheimer's. It is the latest in a long series of attempts to develop a simple test to identify Alzheimer's and conclusively distinguish it from other forms of dementia or neurological disease. But the value of the Nymox test, which costs $400, is still not clearly proven. And it comes up with a false-positive reading 11% of the time. The controversy about the way it has been publicized, however, has overwhelmed the scientific debate.
Dr. Norman R. Relkin, an Alzheimer's specialist who directs a memory-disorders program at New York Hospital-Cornell Medical Center, says hawking the test to the public is "reprehensible." The Alzheimer's Assn. derides Nymox' "highly objectionable" sales efforts and advises against use of the test, which, because it is not a product, needs no government approvals.
UNDETERRED. Nymox, however, is determined to triumph over its critics. It is going mainstream both in its marketing and its science. It helped fund a study of the test at Massachusetts General Hospital that it says proves its worth. Armed with the study, the company is shifting to a more subtle marketing tactic: the scientific meeting. On Mar. 16, it plans to host the Manhattan Alzheimer's Disease Conference, bringing several hundred doctors, caregivers, and others together with leading Alzheimer's researchers from Britain, Canada, and the U.S.
Reaction to the test at that meeting will be a bellwether for Nymox' own fortunes. The company was founded in 1985 by CEO Dr. Paul Averback, a neuropathologist who owns about 70% of the stock. Although it has several products in development, the NTP test is the only one on the market. Nymox went public in 1995 by taking over a shell company whose stock traded in Montreal, then watched its stock soar on the Montreal Exchange from $2.45 (U.S.) to a high of $13.50 in mid-1996 on company publicity about the then-unpublished Mass General study. As attacks mounted, the stock drifted down--Nymox was launched on NASDAQ last November at $6.31 and now hovers at about $6.
The Nymox story is more than a medical catfight. It shows how commercialism and science can come into nasty conflict. According to U.S. studies, half of all people who reach 90 will develop Alzheimer's, for which there is no known cure. A reliable test could someday be worth hundreds of millions of dollars. Doctors could use it to differentiate between patients suffering from Alzheimer's and those with more readily treatable causes of dementia--such as depression, thyroid problems, or even vitamin deficiency--while drugmakers could use it to assess new therapies.
SKEPTICISM. For 25 years, researchers have sought such a test, only to be disappointed. Another hot prospect, a test for the apolipoprotein E (APOE) gene that is believed to be linked to Alzheimer's, is seriously flawed and can neither predict nor unquestionably confirm the disease, according to the Alzheimer's Assn. Clouding the picture further, in the March issue of Nature Genetics, a research team at the University of Pittsburgh reports that people with two copies of a gene called bleomycin hydrolase-g are four times as likely to have Alzheimer's as those with only one copy. The new gene, however, appears to cause Alzheimer's only in people who don't have the APOE gene.
Against such a confusing background, skepticism about the Nymox test is widespread. Nymox acknowledges that the test will yield false positive results in at least 11% of cases. Since no current test is free of such errors, misdiagnoses could abound, and the chance to treat less dire causes of memory loss or dementia would be lost. Harvard Medical School neurologist Peter Lansbury notes: "A false positive for Alzheimer's is a nightmare."
Plenty of people, moreover, may find the test--now done through a spinal tap and eventually through a urine sample--redundant. When symptoms are apparent, the test's accuracy is little better than that of a neurologist's routine screening. What's more, since there is no cure for Alzheimer's and only modestly helpful treatments, a slight boost in certainty about a diagnosis won't make any practical difference in therapy. Researchers at privately held rival MitoKor Inc. in San Diego say they won't make a test of theirs available publicly until there's a useful drug to go along with it. Says Robert E. Davis, MitoKor's chief science officer: "We see little utility in identifying patients if you can't do something for them." Instead, the company contracts with drugmakers who use its test in their own clinical studies.
However flawed the Nymox test may be, the research that underlies it has promise. Neurobiologist Zaven S. Khachaturian, who heads the Alzheimer's Assn.'s Ronald & Nancy Reagan Research Institute, says that the Mass General study of NTP levels, published in December in the Journal of Clinical Investigation, is "a very solid piece of science," that could someday spawn a reliable diagnostic test. But this lone study, he and others argue, needs to be replicated, and any test developed out of it needs to be refined.
RESERVATIONS. Besides, say critics, too many questions remain about NTP: For example, what do varying levels of the protein mean in patients, and is it common in many non-Alzheimer's dementias? "The claim that now we can rule out Alzheimer's disease with certainty is simply not substantiated by the data," argues Relkin. Khachaturian questions whether "the marketing effort is warranted by the strength of the scientific evidence." Even clinicians who back the test have reservations. Dr. Eric A. Awad, an Atlanta neurologist, has used the test to help rule out Alzheimer's in three patients--just as Nymox maintained he could. "For lack of better choices at this time, it's a pretty valid test," he maintains. "Unfortunately, we do not have enough information on it."
Averback, a former emergency-room doctor, blames overcautiousness for some of this resistance. As for his unconventional marketing, he argues that the public has a right to know about new developments, and "some doctors are slower than others" to adopt breakthroughs. Suzanne de la Monte, lead author of the Mass General study, agrees that "people in the neurology and the Alzheimer's field are very slow to wake up to something brand new." And, she adds, Nymox' critics "may still be a little miffed" about the ads running before the research had been published.
But reservations persist even after publication of the study. "We need to learn more before I think this is useful," says Peter Davies, a pathology professor at Albert Einstein College of Medicine who is scheduled to speak at Nymox' upcoming New York meeting. In its rush to market, Nymox seems more interested in cashing in on the data it has rather than learning more. A slower course might produce a test that no one would say is ahead of its time.