A new study led by scientists at Rutgers University – New Brunswick has demonstrated an exciting new gene therapy treatment that stimulates inner ear stem cells into becoming auditory neurons. The technique could potentially reverse hearing loss in many people, but the researchers urge caution as the stimulation of these stem cells could also have major side effects, such as increased cancer risk.

"It's a cautionary tale," says senior author of the study Kelvin Kwan. "People say, 'we'll just put stem cells in and we're going to replace lost neurons.' We're saying that 'yes, we can make neurons,' but you have other side effects that are unanticipated, such as increased proliferation of stem cells."

The Rutger team's work focuses on over-expressing a gene called NEUROG1, which plays a role in the development of auditory neurons, or spiral ganglion neurons (SGNs). These neurons can either be damaged from prolonged exposure to loud noise or age-related degeneration, and when they're gone they don't regenerate.

The team discovered that over-expressing NEUROG1 does successfully result in a proliferation of SGNs that could restore hearing in a human subject, but this also has problematic side effects.

"... since that leads to increased cell division and NEUROG1 is used in other stem cells to make other types of neurons, scientists in other fields should be aware that when using this factor, they'll probably also increase cell proliferation," warns Kwan.

To try and mitigate these side effects, the researchers found that managing the chromatin state of targeted genes successfully helped reduce undesirable stem cell proliferation. Chromatin is a molecule complex comprised of DNA and histone proteins.

"Ideally, we would change the chromatin state before we start overexpressing NEUROG1 and prevent unwanted stem cell proliferation," suggests Kwan.

Ultimately, this study offers scientists working with stem cell therapies a fair warning into how the treatment can be a double-edged sword. As Kwan points out, this is a cautionary tale that may not apply to all forms of stem cell research, but is a strong reminder that there is still great deal of work to do before we can safely and confidently deploy these treatments widely.

The study was published in the journal Stem Cell Reports.

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