US Pharm. 2020;45(1):5.

In December, scientists reported on a pair of gene-therapy breakthroughs that hold the potential to treat various brain-related diseases, such as tumors and amyotrophic lateral sclerosis (ALS), and possibly Alzheimer’s, Parkinson’s, and other neurologic disorders.

Ohio State University scientists reported a gene-therapy technique that transforms human cells into mass producers of tiny nano-sized particles full of genetic material. The technique, they say, promises to deliver targeting drugs and reverse diseases. The experimental therapy slowed tumor growth and enhanced survival in mice with gliomas, which are responsible for the mainstay of human malignant brain tumors.

The patented innovation employs exosomes, fluid-filled sacs that cells release to communicate with other cells. They do not induce an immune response, an additional advantage. When they are injected into the bloodstream, they know exactly where to find their target in the brain. The research was reported in Nature Biomedical Engineering.

“Think of them like Christmas gifts: The gift is inside a wrapped container that is postage paid and ready to go,” said senior study author L. James Lee, professor emeritus of chemical and biomolecular engineering at Ohio State. And they are gifts that keep on giving, Lee noted: “This is a Mother Nature–induced therapeutic nanoparticle.”

In 2017, Lee and colleagues discovered a regenerative medicine technique called tissue nanotransfection, a process that uses a nanotechnology-based chip to deliver biological cargo directly into skin, an action that converts adult cells into any cell type of interest for treatment within a patient’s own body. Experiments in mice showed the exosomes were far more likely to travel to the brain tumors and slow their growth compared with control substances.

Resulting from exosomes’ harmless access to the brain, Lee said, this drug-delivery system has promise for treating neurologic diseases such as Alzheimer’s and Parkinson’s.

In other gene therapy–related news, late last year researchers from the University of California San Diego School of Medicine found that injecting a virus-delivered gene silencer blocks ALS degeneration and preserves motor function in adult mice. Previous research has suggested that SOD1 gene mutations may cause motor neuron cell death, resulting in ALS. The new approach involves injecting shRNA, an artificial RNA molecule capable of silencing a targeted gene, that is delivered to cells by means of a harmless adeno-associated virus.

In this work, single injections of the shRNA-carrying virus were placed at two sites in the spinal cord of adult mice expressing an ALS-causing mutation of the SOD1 gene, either just before disease onset or when the animals had begun showing symptoms. The scientists reported in Nature Medicine that the process suppresses the degenerative motor-neuron disorder if treatment vector is delivered prior to disease onset and blocks disease progression in adult animals with symptoms.

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