Children affected by the Down Syndrome (DS) carry three copies of chromosome 21 which hosts the same gene that in Alzheimer Disease (AD) is responsible for the accumulation of beta-amyloid in the brain. Amyloid plaques start depositing in the brain very early and by age 40 the amyloid is widely accumulated in their cortex, contributing to a risk of developing AD dementia. Patients with DS now live longer than before and AD has become their main cause of death. Seventy per cent of DS patients develop dementia before they die. No treatment is presently available to slow down or to stop the disease.
Due to the concomitant cognitive deficits, testing dementia treatments in DS patients is more difficult than in AD. The psychological tests developed to measure the efficacy of therapies in AD do not work for DS because these patients have grown up with cognitive impairment and their mental deficit varies greatly from one to another. Fortunately, the same fluid (plasma and cerebrospinal fluid ) as well as the same imaging ( MRI and PET ) biomarkers seems to work for both diseases.*
Despite these difficulties, the striking similarity of pathology between the two diseases has encouraged drug companies such AC Immune to test the first therapy for DS as anti-abeta amyloid immunization.* The first Phase 1 trial recruited 16 individual with DS, ages 25 to 45 who did not jet develop dementia, to be treated for a year.
The company selected an active vaccine because it is anticipated that the therapy will have to continue over a long time and one single immunization per year would be more cost effective. A second Phase 2 trial is planned by the same company in the US and Europe in 73 young adult DS patients who have a positive amyloid PE scan.
Several other amyloid-targeting approaches are being contemplated by other companies. Therefore, it is probable that other clinical trials on several hundreds of DS patients will follow in the next few years.
Review written by Ezio Giacobini, MD, PhD
From : In Down’s Syndrome, amyloid vaccine opens door to trials, in Alzforum Network, 20 May 2021, part 1* and part 2**