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

immunosupressants

Repurposing a transplant drug for bone growth

The transplant immunosuppressant drug FK506, also known as tacrolimus or Prograf, can stimulate bone formation in both cell culture and animal models. This info comes from orthopedics researcher Nick Willett, PhD and colleagues, published in International Journal of Molecular Sciences (open access).

Nick Willett, PhD

The results suggest that FK506 might be repurposed as a “stand-alone” replacement for recombinant BMP-2 (bone morphogenic protein 2). That product has been a huge commercial success for Medtronic, in the context of spinal fusion surgeries, although controversial because of cost and side effects.

BMP-2 is more potent gram for gram, but FK506 still may offer some opportunities in local delivery. From Sangadala et al (2019)

One of Willett’s co-authors is orthopedics chair Scott Boden, MD, whose lab previously developed a system to search for drugs that could enhance BMP-2. Previously, other researchers had observed that FK506 can enhance the action of BMP-2 – this makes sense because FK506’s target protein is a regulator of the BMP pathway. Willett’s team used FK506 on its own, delivered in a collagen sponge.

“That is the big finding here, that it has the potential to be used on its own without any BMP-2,” he says.

The sponge is a possible mechanism for getting the drug to tissues without having too many systemic effects. Willett’s lab is now working on refining delivery, dosing and toxicity, he says.

Willett, based at the Atlanta VA Medical Center, is in the Department of Orthopedics and the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory. He and Sree Sangadala, PhD (first author of the IJMS paper) currently have a grant from National Center for Advancing Translational Sciences on this project.

 

 

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Tailoring transplant drugs for children

For adult organ transplant recipients, juggling a lifetime regimen of immunosuppressant drugs is difficult enough, but for children it presents an even greater challenge.  These drugs, which also can have toxic side effects, must strike a delicate balance between preventing organ rejection and protecting from infections.

But children’s immune systems are still “learning” what distinguishes them from the world around them, and children are constantly developing and changing, both physically and emotionally. This puts them at greater risk for complications either through inappropriate medication or failure to take these drugs properly.

A grant from the National Institute of Allergy and Infectious Diseases (NIAID), through the American Recovery and Reinvestment Act (ARRA), will support new studies at Emory University and Children’s Healthcare of Atlanta to help clinicians tailor therapies specifically for children receiving transplants.  The project will include hiring of additional personnel to undertake these studies.

Allan D. Kirk, MD, PhD, is principal investigator of the project, which is supported by a two-year grant of nearly $1.65 million. Kirk is professor of surgery and pediatrics in Emory University School of Medicine and a Georgia Research Alliance Eminent Scholar. He also is vice chair of research in the Department of Surgery and scientific director of the Emory Transplant Center.

The ARRA-funded project will not only help determine which medications children should take, but also will give them the support to care for their transplanted organs.  The Emory scientists are studying new biological monitoring technologies that can identify unique ways to determine exactly how much medication a child really needs. These studies are being combined with a novel transition care clinic specializing in helping children cope with their illness and assuming responsibility for their care.

“This award indicates exceptional insight by the NIAID into the critical link between a child’s physical well-being and their emotional maturity,” says Kirk. “It will accelerate progress in this vital area of research for a very deserving subset of chronically ill children.”

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