The following guest post is from one of our contributors, Dr. Susan Molchan, a psychiatrist in the Washington D.C. area.
As half of the face of a pretty middle-aged woman dissolves into the background of an October 2010 TIME magazine cover, the headline proclaims, “At last, some progress against the most stubborn disease — Alzheimer’s.”
Cover articles in TIME magazine have always been — and still are, even in a changing media landscape — a big deal. But as someone who follows research on Alzheimer’s disease closely, I have to wonder: Did the message that was conveyed merit such a prime piece of cultural real estate?
That 2010 cover article focused primarily on drugs that target pathological deposits of the protein amyloid. Since that article’s publication, these drugs have been tested in large studies that have so far ended in crushing disappointment. And yet this week, TIME’s cover again dramatizes potential Alzheimer’s treatments with a silhouetted face in profile about to swallow a glowing blue capsule. Is the magazine building up hopes that are likely to get dashed once again by an encounter with reality?
The story promises “a radical new approach,” and quotes Dr. Frank Longo of Stanford University as being frustrated (to the point of tears) “that we’ve cured Alzheimer’s in mice many times.” Yet the only shred of evidence given for the promise of Dr. Longo’s new drug, referred to as LM11A-31, is that it has positive effects in mice. The drug is just now being tested in people with Alzheimer’s disease, in phase II trials. Many drugs have gotten through phase II trials, only to fail in the larger, longer phase III trials.
Dr. Longo’s drug doesn’t target amyloid, and the story does a good job of explaining this. It quotes a well-known Alzheimer’s researcher, Dr. Ronald Petersen of the Mayo Clinic, who speculates the drug may stimulate growth factors to help preserve connections among nerve cells. For anyone quoted, though, it’s important to establish if they have a financial conflict of interest in either Dr. Longo’s company, PharmatrophiX, or any other drug company. And in Dr. Petersen’s case, he has previously disclosed relationships with a number of companies developing Alzheimer’s drugs including Roche, Merck, and Genentech. Billions continue to be funneled into drug development for Alzheimer’s disease because it’s projected to be a $20 billion/year market. Like Dr. Petersen, most academics doing clinical Alzheimer’s research are paid consultants to pharmaceutical companies. We only hear the rosy side of the story in TIME, with no comments on drawbacks or possible side effects. If the rosy bit warrants a cover story, balance demands a comment regarding possible downsides. Growth factors, for example, can promote cancer.
The researchers interviewed also surmised that this new drug, targeting its cascade of badness, might be swallowed together with a drug targeting amyloid, and yet a third targeting the tangles of the protein tau — creating a “new Alzheimer’s cocktail.”
I would definitely toast any drug or drugs that halted the progression of the disease with tolerable side effects, but the prospects for this are poor. Most older people already take several drugs, and are particularly susceptible to side effects, a significant cause of hospitalization and death. Also, with the way prices of new drugs are running, we may be talking hundreds of thousands of dollars a year. Young people will need a cocktail or two when they see what Medicare is costing, if it even survives the potential “game changers” described by TIME.
A drug may be approved by the FDA that doesn’t even work, or work very well, but which still costs hundreds of thousands of dollars a year. This might be fine for Dr. Longo and his company, which if it makes it through phase II may well be purchased by a large pharmaceutical company for further development and marketing of the drug.
Ineffective drugs are approved on the basis of “surrogate endpoints,” which we hope are indicators or markers for what will actually help people. Cholesterol levels are one example where these work, as lower levels predict less heart disease. But as journalist John Fauber has pointed out, many cancer drugs shrink tumors but end up not affecting survival or quality of life. (We profiled Fauber recently in one of our podcasts on health journalism standouts.)
This is a boon for drug companies, but not for patients, and some scientists think it discourages innovation, as companies tend to continue to take this easy route to approval, a sort of “teaching to the test” of FDA approval rather than towards clinically meaningful benefits.
As the TIME article notes, of 200 drugs tested none have materialized as the “silver bullet.” Traditionally Alzheimer’s has been considered as the most common cause of dementia, responsible for 60-70% of cases. Most people with dementia are in their 80s (the 2010 TIME cover and movies like “Still Alice” aside). According to most dementia experts, “the vast majority of dementia cases, especially those occurring late in life, tend to involve a mixture of Alzheimer’s disease, vascular disease, and other degenerative factors.” No wonder no drug has worked.
This week’s TIME article notes interesting results from a longitudinal study at Rush University Medical Center indicating that increasing levels of the nerve growth factor BDNF might be helpful for Alzheimer’s disease. Although TIME notes, “There is no drug that boosts BDNF levels . . . ” it is a well known effect of anti-depressants and thought to be involved with their mechanism of action. They unfortunately have not been found to help with memory problems in Alzheimer’s disease. Another way to increase BDNF: exercise. This is very well documented in studies of mice and rats, and understandably harder to document in the brains of humans, so results are more mixed.
The article mentions exercise, but only in two sidebars entitled “Longevity Pro Tips”, and it only offers anecdotes from scientists saying what they do for exercise. It makes one wonder, do they know something the author isn’t telling us? In a larger sidebar, “Other strategies for fighting Alzheimer’s,” we have more drugs, drugs, and drugs, even though there’s good evidence that non-drug interventions (exercise is one) may be helpful via the same mechanisms proposed, such as fighting inflammation and improving blood sugar regulation.
This month scientists from Boston University published findings from the Framingham Heart Study, showing that the number of new cases of dementia decreased by 44% in recent years compared with the late 1970s. Many other studies, especially from developed countries in Europe, have also shown that dementia rates are dropping. Researchers think part of this is due to improved heart and blood vessel health as people smoke less and control blood pressure and cholesterol levels. Education and/or socioeconomic class also appear to have something to do with it. In Framingham, for example, the decline in incidence was seen only in those who had graduated from high school.
“If a 25 percent risk reduction were to be observed for a drug tested in a prevention clinical trial then we would be talking about a clinically meaningful effect as if it were a ‘cure’,” commented Dr. Lon Schneider, an Alzheimer’s researcher at the University of Southern California at AlzForum.org.
Time did report on the dropping dementia rate from the Framingham study in a short article in the February 10 issue of TIME and quoted one of the scientists: “We need to look at preventive research with as much enthusiasm as we need to look at treatment modalities.”
Maybe someday research like that coming from Framingham, that actually reports results in humans, will make the cover of TIME.