BARCELONA, Spain — A drug for treating HIV may also have the ability to help individuals with Down syndrome who deal with cognitive impairment. Researchers say tests on mice reveal that lamivudine improves cognition, which is a key problem for people with the genetic condition.
Lamivudine is a prescription medication approved for use in the United States to treat HIV infections in both adults and children. Researchers are hoping to start clinical trials in human patients in a near future.
What is Down syndrome?
People with the condition have an extra chromosome in their bodies. Typically, a child only has 46 chromosomes at birth. However, babies with Down syndrome have an extra copy of the 21st chromosome.
Unfortunately, this copy leads to children having mild to moderate intellectual disability, including problems with memory, speech, and attention span. During adulthood, these individuals also experience accelerated aging, which leads to cognitive decline more rapidly than in other older adults.
This puts people with Down syndrome at a much higher risk for the development of Alzheimer’s disease later in life. Specifically, researchers say chromosome 21 carries a gene — amyloid precursor protein (APP) — that creates amyloid proteins. Previous studies have shown that these proteins build up in the brain and lead to declining mental performance.
Amyloid accumulation is a common problem in most adult Down syndrome patients over the age of 40.
How do doctors treat patients with Down syndrome?
Currently, one of the few options available to help people with Down live independently is a psychosocial intervention like cognitive stimulation therapy. Study authors note that there are no drug treatments that can do this at the moment.
However, scientists are now looking at targeting retrotransposons in Down syndrome research. Retrotransposons are segments of DNA which change location inside a genome. The segments do this by making RNA copies of themselves, which then jump into another location on a DNA strand. Through this process, retrotransposons are able to insert themselves into specific genomes and position themselves in gene-promoting regions which have a connection to neurodegenerative diseases. This actually enhances their activity in the body.
The speed at which retrotransposition takes place also increases as someone gets older and more cells die off. This is where the connection to HIV comes in. Retrotransposons are similar to the virus, as they replicate rapidly inside cells.
Blocking retrotransposons may treat Down syndrome
Since lamivudine helps to inhibit HIV from replicating, the researchers examined the drug’s ability to do the same with retrotransposons in mice.
“Both HIV and retrotransposons need the same molecule to make copies of themselves: the reverse transcriptase enzyme,” explains Dr. Bonaventura Clotet, Director of the IrsiCaixa AIDS Research Institute, in a media release.
“We know that lamivudine, a reverse transcriptase inhibitor used against HIV, was shown in aged mice to decrease the activation of retrotransposons which could be linked to age-associated disorders. Therefore, we thought that it could be useful to counteract the cognitive impairment associated with Down syndrome.”
The team used Ts65Dn mice, which are the most studied Down syndrome animal models available for research. Over four months, one group of mice received lamivudine treatments, while a control group only consumed a placebo (water).
During behavioral experiments testing their motor activity, memory, and levels of anxiety, the team found mice on lamivudine enjoyed greater levels of cognitive function. Researchers believe the drug is targeting at least one variant of the APP gene.
“Our work aims to support people with Down syndrome and their families by providing them more options to live independent lives, particularly those affected by early-stage Alzheimer’s disease,” says Dr. Mara Dierssen, researcher at the Centre for Genomic Regulation in Spain.
“We still need pharmacological treatments that consistently help improve memory, attention and language functions, or prevent cognitive decline associated with ageing. This study is one step aiming to change that, revealing retrotransposition as an interesting mechanism to pursue not only in ageing but also in neurodevelopmental disorders,” Dr. Dierssen concludes.
The study is published in the Journal of Cellular and Molecular Medicine.