Most people are now aware of at least some of the more daunting facts about Alzheimer’s disease:
- About six million people are now affected by it — a tally estimated to double by the year 2060.
- Nearly one of five Medicare dollars is spent on people with dementia; that amount is expected to rise to one in every three dollars by 2050.
- While the disease progresses differently in different people, a person with Alzheimer’s lives for an average of four to eight years after diagnosis, but can live as long as 20 years.
- Given the current state of available treatments, it’s estimated that one in three seniors will die from Alzheimer’s or some other dementia.
Another hard truth is there are currently no medications that can cure Alzheimer’s — or even stop it from progressing. At the recent “Aging in America” conference sponsored by the American Society on Aging, a panel of neuroscientists, medical researchers, and healthcare advocates sat down to explain to a capacity crowd why that is true.
What’s Available Now
There are currently 87 pharmaceutical treatments for Alzheimer’s in development, but only a handful have been approved by the U.S. Food and Drug Administration (FDA), and each of them have limitations and recommended applications.
To understand how the drugs are meant to work, it helps to know a bit about how Alzheimer’s acts to make the brain stop working. Simply put, in a healthy person, nerve cells called neurons connect at synapses in the brain, where chemicals called neurotransmitters act as messengers, relaying information from one cell to another. Alzheimer’s disease kills neurons and destroys synapses, disrupting the brain’s ability to communicate; a person in the end stages of the disease actually loses about 1/3 of the brain’s mass.
There are two main types of drugs currently used to treat Alzheimer’s.
Cholinesterase inhibitors slow down the process that breaks down neurotransmitters. They are prescribed to treat symptoms related to memory, thinking, language, judgment, and other thought processes.
Receptor antagonists block the excess neurotransmitters that Alzheimer-damaged cells often release. They are advised for patients in the later stage of the disease memory, attention, reasoning, and the ability to perform simple tasks from start to finish.
Five drugs, each aimed to work in a distinct way at various stages of the disease, are currently FDA-approved.
|Drug name||Brand name||Approved||Used to treat||How it works|
|Donepezil||Aricept||1996||All stages||Cholinesterase inhibitor|
|Rivastigmine||Exelon||2000||All stages||Cholinesterase inhibitor|
|Galantamine||Razadyne||2001||Mild to moderate||Cholinesterase inhibitor|
|Memantine||Namenda||2003||Moderate to severe||Receptor antagonist|
|Memantine||Namzaric||2014||Moderate to severe||Both inhibitor & antagonist|
Common side effects of all these drugs may include nausea, vomiting, constipation or increased frequency of bowel movements, headache, and dizziness.
There is much confusion and some controversy over the medications currently used and prescribed. The neuroscientists on the panel at the recent conference on aging expressed skepticism about the efficacy of memantine recommended by some to treat patients with moderate to severe Alzheimer’s, saying it was “still unclear in use.” They also gave less than glowing reviews of the other drugs, noting they gave mild relief to some patients for 1 ½ to 2 years, then stopped working.
But Phyllis Ferrell, vice president of the Global Alzheimer’s Disease Team at Eli Lilly and Company, was quick to convey that scientists are frustrated by newspaper headlines blaring the medical failures connected to Alzheimer’s. “Every one brings us so much closer to success,” she says.
Hurdles to Overcome
A number of factors have increased the challenge of securing a pharmaceutical treatment or cure for Alzheimer’s disease.
Symptoms are usually slow to show. Proteins in the brain begin to clump and nerve cells begin to show damage up to 30 years before a person will exhibit any outward symptoms of Alzheimer’s. By the time many people are actually diagnosed, it is too late for many of them to benefit from drugs aimed to treat symptoms in the early to moderate stages of the disease. And starting treatment too early risks longterm exposure to medications that may have strong side effects.
Drug testing is expensive and time-consuming. It costs about $2.6 billion to bring a medication to bring an Alzheimer’s drug to market, according to Lori Reilly, vice president for Policy, Research & Membership at the Pharmaceutical Research and Manufacturers of America (PhRMA), which represents biopharmaceutical researchers and biotechnology companies. She also notes that since 1998, only four of 123 attempts to bring dementia-related drugs to market have succeeded.
Kenneth L. Davis, a medical researcher who developed the Alzheimer’s Disease Assessment Scale, used to test drugs’ efficacy, is also frustrated by the necessarily lengthy research process. In a thesis titled “How to Accelerate the Search for Alzheimer’s Drugs,” he notes that the rigorous review currently required by the Food and Drug Administration (FDA) from preclinical and animal toxicology through the various phases and analyses of trials can consume up to 24 years — and that’s before a drug is submitted to the FDA for final review and approval.
And Eli Lilly’s Ferrell also points out that it took her company 17 months to get the required 1,000 participants for a particular clinical trial. She says only 50% of those with Alzheimer’s actually get diagnosed; and by then, it is too late for them to qualify for the trials requiring lengthy monitoring.
Little incentive for drug companies. Biomarkers — a smashup of “biological markers” — are the indications of a disease that can be objectively measured and reproduced. Davis laments that Alzheimer’s trials must rely on biomarker indications of the disease rather than an analysis of clinical symptoms, yet the FDA has never approved a medicine solely on biomarker evidence. He says it’s the reason many pharmaceutical companies concentrate instead on “less challenging” diseases: “High-risk, long, costly trials of experimental drugs that leave little patient life once approved hardly make for a compelling business model,” Davis notes. “There is little assurance of the ability to recoup investments, no less earn a profit, even if a company succeeds in the arduous effort of creating, testing, and winning approval of an Alzheimer’s medicine.”