In 2006 the DSRF-UK held a research conference which included Professor Elizabeth Fisher from the Institute of Neurology, UCL  who gave an excellent short summary and presentation on downs syndrome and the use of mouse models.  Last week, a new study was released out of UCL, co authored by Prof Fisher, which is a great example of the insight and benefit of using mice models to gain more understanding in Downs syndrome.

Novel insight into chromosome 21 and its effect on Down syndrome

A UCL-led research team has, for the first time, identified specific regions of chromosome 21, which cause memory and decision-making problems in mice with Down syndrome, a finding that provides valuable new insight into the condition in humans.

“Scientists have traditionally worked on the hypothesis that a single gene, or single genes, was the likely cause of intellectual disabilities associated with Down syndrome.

“We have shown – for the first time – that different and multiple genes are contributing to the various cognitive problems associated with Down syndrome.”

Researchers will now look to discover specifically which gene or genes, within the smaller gene groups, are responsible for impaired memory and decision-making.

Corresponding author Professor Elizabeth Fisher (UCL Queen Square Institute of Neurology) said: “Our study provides critical insights into
the mechanisms underlying neuro-disability in Down syndrome and indicates that intellectual disability in Down syndrome may result from different underlying genetic, functional and regional brain abnormalities.

“This implies that therapies for people with Down syndrome should perhaps target multiple processes, and we have made the initial steps in identifying what some of these processes are.”

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Low Dose Lithium May Stop Alzheimer’s Disease in Its Tracks

 

In a new study, however, a team of researchers at McGill University led by Dr. Claudio Cuello of the Department of Pharmacology and Therapeutics, has shown that, when given in a formulation that facilitates passage to the brain, lithium in doses up to 400 times lower than what is currently being prescribed for mood disorders is capable of both halting signs of advanced Alzheimer’s pathology such as amyloid plaques and of recovering lost cognitive abilities. The findings are published in the most recent edition of the Journal of Alzheimer’s Disease.

Encouraged by these earlier results, the researchers set out to apply the same lithium formulation at later stages of the disease to their transgenic rat modeling neuropathological aspects of Alzheimer’s disease. This study found that beneficial outcomes in diminishing pathology and improving cognition can also be achieved at more advanced stages, akin to late preclinical stages of the disease, when amyloid plaques are already present in the brain and when cognition starts to decline.

“From a practical point of view our findings show that microdoses of lithium in formulations such as the one we used, which facilitates passage to the brain through the brain-blood barrier while minimizing levels of lithium in the blood, sparing individuals from adverse effects, should find immediate therapeutic applications,” says Dr. Cuello. “While it is unlikely that any medication will revert the irreversible brain damage at the clinical stages of Alzheimer’s it is very likely that a treatment with microdoses of encapsulated lithium should have tangible beneficial effects at early, preclinical stages of the disease.”

Moving forward

Dr. Cuello sees two avenues to build further on these most recent findings. The first involves investigating combination therapies using this lithium formulation in concert with other interesting drug candidates. To that end he is pursuing opportunities working with Dr. Sonia Do Carmo, the Charles E. Frosst-Merck Research Associate in his lab.

He also believes that there is an excellent opportunity to launch initial clinical trials of this formulation with populations with detectable preclinical Alzheimer’s pathology or with populations genetically predisposed to Alzheimer’s, such as adult individuals with Down Syndrome. While many pharmaceutical companies have moved away from these types of trials, Dr. Cuello is hopeful of finding industrial or financial partners to make this happen, and, ultimately, provide a glimmer of hope for an effective treatment for those suffering from Alzheimer’s disease.

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