A novel approach to gene therapy is improving lives in ways once thought impossible. Researchers at The Ohio State University Wexner Medical Center and College of Medicine have developed a new platform to deliver the gene therapy precisely to specific areas of the brain.
Their research builds on previous work at Ohio State and the University of California San Francisco using targeted delivery of gene therapy to the midbrain, near the brainstem.
Some of their research now focuses on patients with Alzheimer's disease and Parkinson's disease. Worldwide, more than 55 million people have Alzheimer's disease, according to the World Health Organization. Another 10 million have Parkinson's disease, the second-most common neurodegenerative disease after Alzheimer's disease, according to the Parkinson's Foundation.
One of their biggest successes uses gene therapy to treat a rare genetic disorder called aromatic L-amino acid decarboxylase (AADC) deficiency.
Children with AADC deficient are missing the enzyme that produces dopamine and serotonin in the central nervous system. This affects pathways in the brain responsible for motor function and emotions.
As a result, these children can't coordinate the movements of their head, face and neck. They often don't reach normal childhood milestones, such as sitting up or walking by themselves.
Fewer than 1,000 people worldwide are estimated to have AADC deficiency, according to the Genetic and Rare Diseases Information Center. One of them is 9-year-old Delilah Ramirez.
Along with her mother, Arcelia Ramirez, they traveled 800 miles from their home near Omaha, Neb., so that Delilah could have this life-changing gene therapy surgery at Ohio State Wexner Medical Center.
At the time of the surgery in July 2022, Delilah couldn't hold up her head or sit up by herself. She relied on a motorized wheelchair to move around. She couldn't feed herself, or sleep through the night. She had emotional outbursts, and suffered from seizure-like episodes that could last for hours.
But now, Delilah has changed so much – for the better. On her 9th birthday, she blew out a candle on her cupcake – on purpose. This was the first time she had ever blown out a birthday candle.
She's like a different kid. Her sleeping is a lot better. She can walk now, she can self-feed. When she started using a fork, that was a reason to celebrate. When she started using a straw, that was a reason to celebrate. Walking was a big, big milestone for her that we just celebrated."
Arcelia Ramirez
AADC deficiency is one of thousands of diseases caused by genetic mutations. Krystof Bankiewicz, MD, PhD, professor of neurological surgery at Ohio State, says it's like a typo in Delilah's DNA.
"So we are bringing in a correctly spelled sequence of the gene," said Bankiewicz, who is also chief scientific officer at the Ohio State Gene Therapy Institute.
To do that, neurosurgeon James "Brad" Elder, MD, and his team at Wexner Medical Center infuse genetic material directly to precise parts of the brain, tracked in real time through MRI.
"This helps ensure we put the genetic material in exactly the right place, so the brain will start making dopamine and serotonin again," said Elder, who also is a professor of neurological surgery. "This therapy is designed to approach both parts of the brain that control movements and emotions."
This breakthrough in treating patients with AADC was decades in the making.
"It requires a use of the technology and devices that we had to develop and establish over the years to do these surgeries very precisely, very carefully and then do it safely," Bankiewicz said. "The issue of, 'Is it going to work?' It's no longer being questioned. It works."
In addition to expanding this method to central nervous system diseases such as Alzheimer's, Parkinson's, Multiple System Atrophy and Huntington's disease, Elder and Bankiewicz are also trying to edit genetic mutations in other neurological disorders, including brain tumors.
"We are not treating a gene that causes Parkinson's or Alzheimer's," Bankiewicz said. "We're using this technology to deliver a therapeutic that we believe will, in a positive way, affect the progression of the disease."
For more information about gene therapy clinical trials and research, visit the Ohio State Gene Therapy Institute.
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