Most folks think they know about Down syndrome. It involves an extra copy of chromosome 21. It’s the most common chromosome abnormality in humans, present in about 1 in 1000 births. Symptoms include specific facial features, slurred speech, and an IQ of around 50.
But here's something you may not know: People with Down syndrome have an especially hard time as they age. They have a life expectancy of only 50 to 60 years with proper health care, which is bad enough, but they’re also incredibly susceptible to an Alzheimer’s-like type of dementia. Of people with Down syndrome who reach age 60, between 50 to 70 percent of them will develop this dementia. Pretty horrible, considering people with Down syndrome already cope with limited mobility, independence and social interaction.
So it was good to hear that the Massachusetts Institute of Technology recently announced a gift of $3.4 million from the Alana Foundation in Brazil for a research collaboration with Case Western Reserve University aimed at advancing understanding of, and therapies for, Down syndrome.
It’s fabulously interesting stuff, and it takes aim right at the intersection of Down syndrome and aging-linked dementia. Four project areas are planned. In the first, Li-Huei Tsai, PhD, director of the Picower Institute for Learning and Memory at MIT, and Alberto Costa, PhD, director of the Intellectual Disability Program in the Research Institute for Children’s Health at CWRU's School of Medicine, will develop personalized human stem cell models of Down syndrome called iPSCs (induced pluripotent stem cells).
You might’ve heard about iPSCs in 2012, when Shinya Yamanaka won the Nobel Prize for discovering how to make them. Basically, Yamanaka found a way to convert adult cells into stem cells by introducing four key transcription factors. Remember the Bush-era dustup over stem cells? Yeah. Figuring out a non-invasive way to create those fabulously versatile little buggers was a big deal.
But I digress: At MIT, Costa ad Tsai will use these iPSCs to create human neuronal models of Down syndrome in order to better understand the disease. So these guys are basically going to build some brain tissue in the lab (what a world, huh?) and study how it operates with Down syndrome. Neat.
Second, they’ll take this human model and use it to test the benefits of Down syndrome therapies already in the works. It's a preclinical drug screening setup that lets researchers test therapies custom-tailored to different types of Down syndrome.
Thirdly—and this is the real WOW one, for me—Tsai and Costa will breed mice that are genetically protected from Alzheimer’s. They’ll breed mice that mimic Down syndrome. THEN they’ll breed them together to determine if the pathology of the two disorders is comparable. Does Down syndrome have anything in common with Alzheimer’s? They’re going to find out, and their research could open a huge window into how to treat both conditions. Tsai has already shown that limiting the expression of protein p25 in mice can slow many of the typical Alzheimer’s impairments—will mice that have Down syndrome benefit from the same treatment? Finding a link here would enable researchers to effectively hit two birds with one stone—not to get carried away with clichés or anything.
A fourth project will use a 3-D imaging technique to study the anatomy, circuits, and pathologies present in the mouse model of Down syndrome, as well as the human tissue models of the condition.
"There is tremendous opportunity to benefit from our combined strengths — MIT's ongoing research to understand the aging brain, and Case Western Reserve's expertise in Down syndrome," said Tsai, who is also the Picower Professor of Neuroscience in MIT's Department of Brain and Cognitive Sciences. "The Alana Foundation's support will allow us to work together to accelerate research projects with the potential to develop treatments that will improve the quality of life for individuals with Down syndrome."