Treatment and Maybe a Cure for Alzheimer’s
A roundup of the latest research offering hope in the next decade
It's no secret that Alzheimer's and other forms of dementia loom as a potential plague for the nation’s 78 million boomers. We are fast approaching the years when neurodegenerative diseases tend to manifest. By reliable estimates, the number of people with Alzheimer's — now around 5 million — is expected to triple by 2050, and the current $200 million cost is likely to skyrocket to $1 trillion.
In anticipation of a public health crisis, scientists in research labs all over the U.S. are intensively working to crack the codes that will lead to early detection, treatment and, for some people in early stages of the disease, maybe even a cure.
A national plan signed into action by President Obama in 2011 aims for prevention of, or an end to, Alzheimer's by 2025. While that target date is optimistic, myriad trials are yielding promising results.
"This will be the most exciting decade in the history of research in degenerative diseases," says Dr. Dale Bredesen, Augustus Rose Professor/Director of the Mary S. Easton Center for Alzheimer's Disease research at UCLA and author of the first study to document reversal of in patients with early-stage Alzheimer's.
"Arguably, this has been the area of biomedical research that has been the greatest failure in terms of therapeutic development. But for the first time at this point we have enough scientific information to begin to find approaches" that will help those who suffer from the disease, says Bredesen.
Below is a roundup of areas of Alzheimer's study, including information on timing of possible tests and treatments:
Diagnosis of Alzheimer's is typically made when memory and cognitive changes are so pronounced that the disease is in its late stages. "By the time someone is symptomatic they have had the disease for 10 or 20 years and have lost a significant percentage of brain cells and connectivity," says Dr. Keith Black, chairman of the Department of Neurosurgery at Los Angeles' Cedars-Sinai Hospital.
The key, researchers agree, is identifying Alzheimer's in its earliest stages. "The sooner we can intervene, the sooner we can stop the disease at the earliest point," says Dr. Heather Snyder, director of medical and scientific operations for the Alzheimer's Association.
New tools and technologies available in the next few years are likely to hasten early diagnosis of Alzheimer's and other forms of dementia. Two new methods:
- Eye exam: Several studies underway are looking at new technology that will enable ophthalmologists to detect beta amyloid plaque — the sticky buildup that is a major cause of Alzheimer's — via the retina.
- Blood test: Clinical trials are using blood tests to detect an accumulation of tau protein, which strangles healthy nerve cells and leaves behind a tangled mess of dead and dying neurons and is also a primary cause of Alzheimer's.
Several vaccines are in development that aim to prevent beta amyloid from clumping into plaques and help the body clear amyloid from the brain. Most current immunization studies focus on administering antibodies against amyloid from outside sources instead of enhancing a person's immune system.
One large research effort is exploring the value of intravenous infusions of a product derived from donated blood. This product contains naturally occurring anti-amyloid antibodies from the donors. Other studies are investigating laboratory-engineered antibodies.
Insulin resistance and the way brain cells process insulin may be linked to Alzheimer's disease. Researchers are exploring the role of insulin in the brain and closely-related questions of how brain cells use sugar and produce energy. These investigations may reveal strategies to support cell function and stave off Alzheimer-related changes.
Researchers believe that during the disease process, abnormal proteins cause brain cells to become insulin resistant and then die. A body of evidence suggests that this may be reversed with already-FDA approved drugs used in the treatment of diabetes. If successful, these drugs, now on the market, can be immediately administered to Alzheimer's patients. One trial underway is testing the viability of an insulin nasal spray.
The Heart-Head Connection
Growing evidence suggests that brain health is closely related to heart and blood vessel health. The incidence of Alzheimer's increases as a result of conditions that damage arteries such as high blood pressure, heart disease, stroke, diabetes and high cholesterol. Researchers are investigating whether drugs used to treat high blood pressure and diabetes may reduce the risk of developing Alzheimer's.
A major thrust in Alzheimer's research is the "systems approach," which operates on the premise that a constellation of factors, including lifestyle, rather than a single silver bullet, will have an effect on a molecular level on Alzheimer's.
A small trial conducted by UCLA and Buck Institute for Research On Aging in northern California conducted by Bredesen recently demonstrated that memory loss in patients may be reversed — and improvement sustained — using a complex, 36-point therapeutic program that involves comprehensive diet changes, brain stimulation, exercise, sleep optimization, specific pharmaceuticals and vitamins and multiple additional steps that affect brain chemistry.
Bredesen said the findings are “very encouraging,” but added that results are anecdotal; a more extensive, controlled clinical trial is needed.
Currently, there are five FDA-approved Alzheimer's drugs, but these medications do not treat the underlying causes of Alzheimer's as much as temporarily relieve symptoms. Many of the new drugs in development aim to modify the disease process itself by impacting one or more of the wide-ranging brain changes that Alzheimer's causes. These changes offer potential "targets" for new drugs to stop or slow the progress of the disease.
Researchers agree that successful treatment will entail using a "cocktail" of medications aimed at several targets, similar to the most successful treatments for AIDS and many cancers. The caveat: new drugs take years to produce from concept to market — and drugs that seem promising in early-stage studies may not work as hoped in large-scale trials.
Three promising drugs in the pipeline:
- Bapineuzumab (Pfizer and Johnson & Johnson's Janssen Alzheimer Immunotherapy unit): one of the largest bets ever placed in the field of Alzheimer's disease. More than 4,000 patients are participating in four studies around the world — two in people with a gene that raises the risk of Alzheimer's and two in people who don't carry that gene.
- Solanezumab (Eli Lilly): announced results from new analyses of two Phase 3 trials evaluating the relationship between cognitive and functional treatment effects in patients with mild Alzheimer's disease. Based on analyses of the Phase 3 trials, the findings suggested that cognitive deficits were more apparent than functional deficits in mild Alzheimer's disease when measured with the Alzheimer's disease Assessment Scale-Cognitive (ADAS-Cog) and the Alzheimer's disease Cooperative Study-Activities of Daily Living (ADCS-ADL) subscales.
- Pioglitazone: a drug approved for treatment for type 2 diabetes, it's being tested in an Alzheimer's Association trial called TOMORROW, for efficacy in delaying the onset of mild cognitive impairment (MCI). The study is currently recruiting participants.
The Alzheimer's Association has several major trials underway that will hopefully yield additional tools to help in the detection and treatment:
- The Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) Study is designed to test solanezumab and whether an anti-amyloid antibody treatment can slow memory loss associated with amyloid build-up. Enrollment began in March, 2014. Timing: The study is designed to last until 2017, at which time results will be analyzed.
- Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) — an expanded study of A4 follows participants to determine which of their non-amyloid biological changes are related to cognitive decline. LEARN also uses a new tau imaging agent for PET scans that may, for the first time, provide scientists with a diagnostic instrument to assess of the accumulation of tau protein into tangles, a hallmark of Alzheimer's. If successful, tau imaging may help determine where and when the neurodegenerative process begins and its progress in Alzheimer's. Timing: results will be seen around 2017.
- The Dominantly Inherited Alzheimer's Network Trial Unit (DIAN TU), funded in part by the Alzheimer's Association, is testing the safety, tolerability and biomarker efficacy of two drugs, gantenerumab and solanezumab, in individuals who carry the Alzheimer's gene and are likely to develop the disease. The results of this study will have implications for Alzheimer's treatments in people over 65. Timing: the study began in December 2012 and is expected to last until 2016.
Jeanne Dorin is a Los Angeles-based writer who often covers health and wellness.