Alzheimer's disease - tramiprosate
Alzheimer's disease is a distressing form of dementia, whose incidence is rising along with the average age of the population in the developed world. While there is, as yet, no cure, there are a number of medicine that have been shown to have short-term clinical benefits.
Alzheimer's disease is a distressing form of dementia, whose incidence is rising along with the average age of the population in the developed world. While there is, as yet, no cure, there are a number of medicine that have been shown to have short-term clinical benefits.
The disease is linked with damage to the cholinergic neurons in the cortex and hippocampus in the brain, and this leads to a lowering of acetylcholine in the brain. Drug treatments tend to focus on compounds that inhibit the activity of the enzyme that breaks it down, acetylcholinesterase.
A different strategy is being taken by Canadian company Neurochem. It is developing tramiprosate, which interacts with ß-amyloid peptides in the brain. Rather than replacing absent neurotransmitters, it is used to attack the amyloid plaques in the brain that are a characteristic symptom of the disease. Amyloid plaques are predominantly made up of peptide fragments of amyloid precursor protein, which build up because there is an imbalance between production and destruction in Alzheimer's patients. Tramiprosate binds to the soluble ß-amyloid peptides, keeping them soluble and preventing them from being deposited. It may also promote their clearance from the brain.
A double blind, randomised, placebo controlled Phase II trial has been carried out in 58 patients with mild to moderate Alzheimer's disease.1 Tramiprosate was found to be safe at all the doses investigated, up to 150mg twice a day, given in oral doses. The most frequent side-effects were nausea and vomiting, which were both transient and dose related. Levels of ß-amyloid peptides were reduced by up to 70% in those given higher doses.
After three months, 42 patients chose to enrol in an open-label extension of the study, receiving 150mg of the drug twice a day.2 After three years, data from several cognitive function tests suggest that it stabilises cognitive functions, and is particularly effective in patients with mild forms of the disease. Phase III trials are under way.