October 14, 2008
An antihistamine drug once approved in Russia to treat hay fever improved thinking and memory in patients with Alzheimer's disease, experts at Baylor College of Medicine in Houston report. The findings appeared in The Lancet, a medical journal from Britain.
Patients with mild to moderate Alzheimer's disease who were taking the drug, called Dimebon, showed benefit in five critical areas: memory, thinking, the ability to carry out activities of daily living like eating or dressing, behavior, and overall function. Improvements were noted at six months and continued until the end of the 12-month, Phase 2 study, which was conducted in Russia.
By the end of the mid-stage trial, patients treated with Dimebon had not gotten any worse and scored higher on thinking and memory tests, while those taking a placebo continued to deteriorate. "Usually at this point in a drug's development, we are happy to see improvement in one of the outcome measures," said Dr. Rachelle Doody, M.D., Ph.D., professor of neurology at Baylor College of Medicine and lead author of the study. "We saw improvement in all five."
"More research is needed, but we are encouraged by the effect the drug Dimebon had on Alzheimer's patients," Dr. Doody said. The company that makes the drug, Medivation, is continuing follow-up Phase 3 testing in more than 500 patients at various medical centers, including many in the United States. Late-stage testing is not expected to be completed until summer of 2010; if results are positive, only then can the Food and Drug Administration approve the drug for sale at the corner pharmacy.
In the current study, the authors noted that Dimebon is the first drug for Alzheimer's disease that continued to produce improvement in patients over a 12-month period. Other approved drugs for Alzheimer's, like Aricept, Exelon, Namenda and Razadyne, do not have this sustained effect, though new research suggests that these drugs may slow progression of the disease over many years.
In the trial, 183 patients with mild-to-moderate Alzheimer's disease were randomly split into two groups. Half received Dimebon at a dosage of 20 mg three times a day, while the others got a dummy pill. By the end of the study, 12 months later, 120 had completed the trial. Those in the trial were given memory and thinking tests at six months, and again at 12 months, completing such tasks as memorizing a list of words.
"What we saw in the clinical trial is that people on the medication continued to improve over time," Dr. Doody said. "Those on placebo continued to decline."
Researchers believe the medication works by stabilizing mitochondria, which act like tiny batteries to generate energy within the cell. The drug may also act by inhibiting the death of brain cells. In initial studies, it has also shown some potential benefits for patients with Huntington's disease, an inherited movement disorder that becomes progressively worse with age.
In the current trial, the drug appeared to be safe. Nearly one in five participants taking Dimebon complained of occasional dry mouth, and some patients on the drug reported feeling depressed. But no one opted out of the study because of the side effects.
Caregivers, too, appeared to benefit from the healthful effects of the medication on loved ones they cared for. Caregivers reported less distress at six months and one year compared to those who were caring for someone on a placebo. They also spent about one hour less per day on care compared to the placebo group.
"As we continue research, we hope to replicate these results," Doody said. "My belief is that this drug will turn out to be useful for Alzheimer's disease, regardless of the stage of the disease."
Dr. Doody said this is only the first study looking into the effects of Dimebon on Alzheimer's disease. She also noted that it involved only a relatively small population from one specific region of the world. The ongoing Phase 3 study will include several international locations, including the United States.
Patients and caregivers can learn more about that study by visiting Connection Study, or by calling 1-877-888-6386. The company is also recruiting patients for a trial of Dimebon used in conjunction with the popular Alzheimer's medication Aricept. To learn more, visit the National Institutes of Health's ClinicalTrials.gov site. "Combination Therapy with Dimebon and Donzepezil (Aricept) in Patients With Alzheimer's Disease"
Rachelle Doody, et al: "Effect of dimebon on cognition, activities of daily living, behaviour, and global function in patients with mild-to-moderate Alzheimer's disease: a randomised, double-blind, placebo-controlled study." The Lancet, Volume 372, July 18, 2008; pages 207-215. Baylor College of Medicine press office.