For the people who treat neurodegenerative disorders, 2011 is an ominous milestone. That’s when baby boomers begin to turn 65 and face a steeply rising risk of developing Alzheimer’s disease. Over the next 40 years, the number of people with the disease is expected to soar from 5.5 million to 14 million. That long-forecasted boom has spurred dire predictions, including the bankruptcy of the United States’ Medicare system; Alzheimer’s disease already costs the U.S. an estimated $100 billion per year.
No treatments yet exist that temper the progressive brain damage underlying Alzheimer’s, and the few drugs approved for the disease improve cognitive symptoms only modestly. But pharmaceutical companies are working furiously to develop treatments for this massive public-health burden–and potential financial windfall. David Michelson, vice president of clinical neuroscience and ophthalmology at Merck, spoke with Technology Review about the company’s efforts to tackle Alzheimer’s and other neurological diseases.
Technology Review: Alzheimer’s disease is a huge public-health burden but has so far proved difficult to treat. How is Merck approaching the problem?
David Michelson: We have two strategies. How can we intervene with the underlying biology? And can we develop symptomatic treatments for the cognitive changes we see in Alzheimer’s?
Ideally, we’d like to prevent the pathology from forming in the beginning, so we are developing vaccines and other biologics. [Alzheimer’s vaccines work by preventing or clearing the buildup of a protein, known as beta-amyloid, in the brains of Alzheimer’s patients.] But those treatments probably lie the furthest in the future. For the second question, we are targeting the processes that support memory, judgment, and other types of thinking. It may end up that people will need both types of treatment.
The research on memory and cognition is linked to another major focus of the neuroscience program at Merck: schizophrenia. We want to develop new treatments that address the acute illness without the issues of typical antipsychotics [which can cause weight gain and boost diabetes risk], as well as treatments that can improve the more chronic symptoms of schizophrenia and allow people to be more functional. We have a number of compounds in phase II clinical trials for Alzheimer’s and schizophrenia, one or two of which are being tested for both.
TR: Does that mean Alzheimer’s and schizophrenia have something in common?
DM: Alzheimer’s is a global disease that involves memory and executive function. Schizophrenia has a number of characteristic cognitive deficits, such as verbal fluency, even when the person is not psychotic. Our assumption is that there are different properties that underlie those deficits at the base level, but there may be common interventions downstream.
TR: What makes Alzheimer’s such a difficult disease to target?
DM: Alzheimer’s disease progresses slowly and insidiously. By the time you see symptoms, that individual already has significant impairments. So we also have a big effort to identify biomarkers. (See “A Blood Test for Alzheimer’s?”) So we want to identify things that progress with the disease but change more quickly and are less variable. Having these markers will also allow shorter clinical trials.
We are also starting to look at markers for schizophrenia, which probably has several different pathologies. We want to understand who has what and use those markers to select interventions.
TR: Tell me about some of Merck’s drug candidates that are nearing approval.
DM: We have a novel migraine treatment in phase III clinical trials. Migraines are usually treated with tryptans, which are vasoconstrictors. While we don’t know exactly how this compound works, it does not act through this mechanism. In phase II clinical trials, it was shown to be very effective at aborting migraine attacks.
We are also testing a new ophthalmology treatment–a helical intraocular implant device. Right now, if you want to deliver drugs locally to the eye, you must give multiple injections. This device is coated with drugs and can be implanted into the eye, reducing the frequency of invasive procedures. We are currently testing it for diabetic macular edema, but we ultimately plan to use it to deliver novel compounds we are developing for age-related macular degeneration. The benefit is that we can use it to deliver drugs that might be problematic in the body but are okay if delivered in small amounts locally.
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