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Research targets brain disorders such as Alzheimer’s, Parkinson’s

Interdisciplinary CMU team gets NIH funding to deliver DNA to affected cells

| Author: Gary H. Piatek

A team of scientists at Central Michigan University has received National Institutes of Health funding for novel research that has the potential to treat brain disorders, including neurodegenerative diseases such as Parkinson’s and Alzheimer’s.

The goal, fueled by the $433,500 two-year grant, is to devise a way to deliver large DNA fragments into brain cells.

Jumping hurdles: Delivery

Most current research uses adeno-associated viruses to deliver cargo, such as DNA, to cells. The disadvantages of using viruses are that they can carry only small segments of DNA and have potential health risks, said Ajit Sharma, a chemistry and biochemistry faculty member in the College of Science and Engineering.

“In addition, to do the kind of research we and some others are doing, you would need to inject mixtures of multiple viruses,” said Julien Rossignol, a biochemistry and neuroscience faculty member in the College of Medicine.

To overcome the hurdles of safety and size limitations, the team chose to make custom molecules called dendrimers as its delivery tool. They are created in the labs of Sharma and chemistry and biochemistry faculty member Douglas Swanson.

“Our experiments are early stage and require proof-of-principle feasibility studies,” said Dr. Ute Hochgeschwender, a neuroscience faculty member in the College of Medicine. “But they have the potential to lead to a widely useful molecular tool delivery platform for the brain.”

Jumping hurdles: Size

The challenge for Swanson, Sharma and their lab helpers is to figure out how to load a large strand of DNA onto a dendrimer and make the package small enough to get to the targeted cells.

If the packages are too big, the cells in the liver and spleen “will eat them up,” Sharma said. If they are too small, they will be filtered out by the kidneys.

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Senior biochemistry major Rebecca Clark works on DNA/dendrimer formulations in Ajit Sharma's laboratory. "To be able to work on something that might become a major scientific advancement is just amazing," she said.

Student success

Helping with the team’s lab work is senior biochemistry major Rebecca Clark, of Escanaba, Michigan.

Her job is to create DNA/dendrimer formulations for neuroscience lab workers like master’s student Bethany McDonald from Gladstone, Michigan, to feed to cells to see if they take them up.

Once that is successful, they will try it with animals.

It’s the kind of experience that Clark was hoping for when she chose to attend CMU.

“To be able to work on something that might become a major scientific advancement is just amazing,” she said.

Her goals are to earn a doctorate and work in a pharmaceutical lab.

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