Alzheimer’s drug ineffective in Down’s syndrome patients
MedWire News: The Alzheimer's drug memantine is ineffective in treating the disease in Down's syndrome patients, show MEADOWS trial results.
Clinically significant Alzheimer's disease-like features develop in all people with Down's syndrome by the age of 40 years, explain Clive Ballard (King's College London, UK) and colleagues. After memantine, a drug used to treat Alzheimer's in the general population, showed improved learning and memory in Down's syndrome mouse models, the MEADOWS (Memantine for dementia in adults older than 40 years with Down's syndrome) trial was designed to see whether this could be replicated in patients.
Adults over 40 years of age with karyotypic or clinically diagnosed Down's syndrome, with and without dementia, were randomly allocated to receive memantine (n=88) or placebo (n=85) for 52 weeks.
The researchers found that both groups declined in cognition and function, measured using the Down's syndrome attention, memory, and executive function scale (DAMES), and the adaptive behavior scale (ABS) parts I and II.
After adjusting for baseline scores, they found the memantine-treated group's DAMES scores and ABS I scores were 4.1 and 8.5 units lower than the control group's, respectively. The ABS II scores for the memantine group were 2.0 units higher than that of the control group. These differences were not statistically significant.
Adverse events occurred in 11% of the memantine group and 7% of the control group, and again, this difference was not significant. Five participants in the memantine group and four of the controls died, but the number of deaths and overall serious adverse events did not differ between groups.
The researchers say that despite being "well tolerated," memantine does not confer any significant benefits regarding cognition, independent function, challenging behavior, or global outcome in patients with Down's syndrome. They add that this applies to people over 40 years of age with Down's syndrome irrespective of whether or not they have been formally diagnosed with dementia.
"Thus, we do not believe memantine is an effective therapy for the treatment of cognitive decline in people with Down's syndrome," write Ballard and team.
"These results are disappointing, but help to exclude treatments of little benefit and prevent potential side-effects and depletion of scare resources," add Gill Livingston and Andre Strydom, of University College London, in an accompanying editorial published in The Lancet.
The researchers stress the need for research into therapies that are specific to this group of patients and are based on an understanding of the pathologic processes behind them.
By Chloe McIvor