Brain organoid model shows molecular signs of Alzheimer’s before birth

In a model of human fetal brain development, Emory researchers can see perturbations of epigenetic markers in cells derived from people with familial early-onset Alzheimer’s disease, which takes decades to appear. This suggests that in people who inherit mutations linked to early-onset Alzheimer’s, it would be possible to detect molecular changes in their brains before birth. The results were published in the journal Cell Reports. “The beauty of using organoids is that they allow us to Read more

The earliest spot for Alzheimer's blues

How the most common genetic risk factor in AD interacts with the earliest site of neurodegeneration Read more

Make ‘em fight: redirecting neutrophils in CF

Why do people with cystic fibrosis (CF) have such trouble with lung infections? The conventional view is that people with CF are at greater risk for lung infections because thick, sticky mucus builds up in their lungs, allowing bacteria to thrive. CF is caused by a mutation that affects the composition of the mucus. Rabindra Tirouvanziam, an immunologist at Emory, says a better question is: what type of cell is supposed to be fighting the Read more

siRNA

Regrowing adult heart muscle

In adulthood, our hearts generally can’t grow again in response to injury. Emory cardiology researchers Ahsan Husain and Nawazish Naqvi and their colleagues have been chipping away at this biological edifice in animal models, demonstrating that it is possible to remove constraints that prevent the heart from growing new muscle cells.

Husain and Naqvi’s teams accomplished this by combining the thyroid hormone T3 — already FDA approved — with siRNA-based inhibition of an enzyme called DUSP5. Their latest paper, published in the journal Theranostics, applies the combination in an animal model of drug-induced heart failure.

The anticancer drug doxorubicin is sometimes known as the “red devil”

The anticancer drug doxorubicin is notorious for its cardiotoxicity, yet it is a mainstay of treatment for breast cancer in adults and several types of cancer in children. Cardiotoxicity affects a fraction of breast cancer patients treated with doxorubicin (20 percent in some studies) and severely impacts mortality and quality of life.

In the mouse model, doxorubicin generates severe heart failure, with a 40 percent drop in left ventricular ejection fraction (LVEF), a measure of the heart’s pumping capacity. In response to the combination of T3 and DUSP5 siRNA, a large increase in LVEF is seen. The researchers also report that the treatment has a marked effect on the health of the animals, restoring their activity levels, grooming and posture. See the video for an example of a mouse heart treated with the T3/DUSP5 siRNA combination.

The results are potentially applicable to other situations when doctors would want to regrow or repair cardiac muscle. Husain reports plans for a clinical study in patients with drug-induced or other forms of heart failure, supported by a generous gift from the Atlanta-based ten Broeke Family Foundation.

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Posted on by Quinn Eastman in Cancer, Heart Leave a comment