I asked a few researchers to examine the new Salk Institute study on the potential Alzheimer's drug, J147. The biggest question is how much insight can testing the drug in mice provide for human testing.
Greg Sutherland, a neuropathologist at the University of Sydney in Australia, wrote a detailed evaluation of the paper that didn't make it into my article. Because it is so comprehensive, it's worth making available to readers. Because it is so long, it doesn't easily fit as an insert.So instead of placing this into my original story, I'm posting it as a separate blog post and linking back.
For those who want the short version, Sutherland thinks the drug is worth taking into clinical trials. He also praises the study design. However, he cautions that it's far from clear whether the experiments in mice provide a reliable guide to what would happen in human clinical trials.
Sutherland concludes:
"Overall this work advances our present knowledge of AD therapeutics rather than being a ‘revolutionary’ game changer. The study is well performed and addresses an important aspect of AD, namely, symptomatic treatment, at a time when most researchers are turning their attention to preclinical diagnosis and treatment. The latter goals remains elusive at present, but J147 looks ready-made for clinical trials."
And for those who wish to read Sutherland's entire critique, here it is:
The Neurotrophic Compound J147 Reverses Cognitive Impairment In Aged Alzheimer’s Disease Mice
Background
Alzheimer’s disease (AD) is the most common form of dementia with estimates suggesting there will be about 115 million sufferers worldwide by 2050. This rapid increase is due to a combination of an ageing population and the failure of approved therapies such as donepezil to slow or prevent the neurodegenerative process. The symptoms of AD, that include , short term memory deficits result from the loss of neurons. As the disease advances neurons are lost over an increasing proportion of the brain resulting in a wider range of cognitive and eventually motor (movement) deficits.
There are two forms of AD; rare genetic forms that represent less than 5% of total cases and the common sporadic forms. The exact cause of the latter are unknown but the major risk factor is aging. Although AD is not inevitable, about one quarter of the population above 85 years of age will develop the disease. In contrast the rare genetic cases result from mutations in three genes.
These individuals succumb to the disease much earlier. The finding of mutations (first in 1991) allowed the development of transgenic mouse models. Here the human gene or often genes with the mutation(s) is incorporated into mouse embryos and expressed in some of the resulting animals.
These transgenic models are reasonable copies of the human disease but the transgene is permanently on at a single level and this might not equate to the physiological expression seen in humans. Furthermore the transgenic mice don’t experience the neuronal loss seen in the human brain of AD patients.
Overview of Work
Prior et al. based at the Salk Institute have conducted a very elegant study that incorporates many of the features of AD. They have used a double transgenic mouse model (two mutated human genes) but have deliberately waited until these mice are equivalent to old age in humans.
http://news.google.com/news/url?sa=t&fd=R&usg=AFQjCNGST5tqFEeuyI5SU4QRcSswLhXy0A&url=http://www.utsandiego.com/news/2013/may/14/j1467-sutherland-evaluation/
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