A blood test to diagnose Alzheimer’s disease may be moving closer to reality following a recent clinical trial at Cleveland Clinic Lou Ruvo Center for Brain Health.
Kate Zhong, MD, Senior Director of Clinical Research and Development, and her team are working with a French company (ExonHit) to develop a new diagnostic blood test for Alzheimer’s disease. Currently, Alzheimer’s diagnostic tests aren’t performed until the patients exhibit symptoms of the disease. If the test is validated after this study and other tests, primary care physicians will be able to order a simple blood test to identify patients at high risk for the disease.
They recently completed the first U.S. study of the test, a five-month, clinical trial involving 160 participants at three Cleveland Clinic locations. In the test the participants, who have been referred to the Lou Ruvo Center for Brain Health for memory impairment, had their blood drawn and underwent a MiniMental State Exam and evaluation by the Center. The results were compared to data from patients who don’t have Alzheimer’s disease.
“We are very excited about the possibility of contributing to the development of this critically needed new test,” says Dr. Zhong.
Currently, 5.5 million Americans have been diagnosed with Alzheimer’s disease. “One to 2 percent of Americans have Alzheimer’s disease by the time they are 65,” says Dr. Zhong. “By the time they are 85, nearly half will have Alzheimer’s disease if we do not find a more effective treatment.”
Why clinical trials are needed
Clinical trials are the only way that new diagnostic tests and treatments can receive approval from the Food and Drug Administration. All new tests and treatments must first be studied in a laboratory to determine any potential toxicity before human testing begins.
Safe and promising treatments then move into three phases of clinical trials:
- Phase 1 trials involve a small number (20 to 100) of healthy volunteers participate to examine the safety and drug profile of the candidate treatment in human beings.
- Phase 2 trials include a larger number of participants (100 to 300) with the condition to be treated (such as Alzheimer’s disease) who are entered into a trial to determine the safety and preliminary efficacy of the promising treatment. Phase 2 trials also determine the dose to be advanced to Phase 3.
- Phase 3 trials involve large numbers of patients (600 – 2000) with the disease who are given the drug or a placebo to confirm the efficacy of the drug. If Phase 3 succeeds, the drug is advanced for FDA approval after which it can be made widely available.
“Clinical trials are the bridge between bench side (basic research) and bedside (patient use),” Dr. Zhong says.
New drugs and diagnostic approaches for Alzheimer’s disease
The Lou Ruvo Center for Brain Health has approximately 20 drugs and diagnostic processes for Alzheimer’s disease in clinical trials. This is among the largest clinical trials programs in the nation and the world. “One has to have many ‘shots on goal’ to find the one treatment that will help our patients,” says Dr. Zhong.
Currently, the Lou Ruvo Center for Brain Health is testing immunologic therapies for Alzheimer’s disease, enzyme inhibitors for the condition, and neuro-protective agents. These are all disease-modifying agents intended to delay the onset or slow the progression of the disease. Dr. Zhong’s group is also studying treatments for agitation in Alzheimer’s disease, a common problem for which there is no current approved treatment.
Another means of developing new drugs for Alzheimer’s disease is to use drugs approved for other conditions that may benefit patients with Alzheimer’s disease.
For example, the cancer drug bexarotene was shown to have a dramatic effect in laboratory testing of Alzheimer’s disease. The drug is already approved for treatment of cancer and the Lou Ruvo Center for Brain Health team has constructed a Phase 2 trial to test the drug in patients with Alzheimer’s disease. The use of repurposed drugs accelerates the time frame for Alzheimer’s disease treatments and may help get drugs to patients more quickly.
The role of philanthropy
“The process of new drug and diagnostic device development is slow and often frustrating,” says Dr. Zhong, “but the care with which clinical trials are conducted is important to assure the public of their safety and utility.”
If the results of the clinical trial for the Alzheimer’s disease diagnostic blood test are promising, a Phase 3 clinical trial may be next.
“Large Phase 3 clinical trials cost millions of dollars,” says Dr. Zhong, “and the full development of a drug from initial discovery through FDA approval can cost in excess of a billion dollars.”
“Personal philanthropy, however, can make a significant difference,” says Dr. Zhong. “Individuals who support our studies allow us to do preliminary testing to know whether a drug or mechanism should be further studied in Alzheimer’s disease. Individual donors can have an important impact on helping to find new treatments and diagnostic approaches to Alzheimer’s disease.”