Gene therapy tries to replace, repair, augment or manipulate a patient's own genes with the goal of treating illness. The technique not only can save lives but also can treat chronic conditions such as hearing impairment.
Hearing loss affects roughly 28 million Americans because the nearly 50,000 inner ear hair cells that humans are born with die off gradually over time. Unlike those hair cells in fish, amphibians and birds, those of mammals cease proliferating early in life, meaning hearing loss is usually permanent. Two research teams have demonstrated the possibility of regrowing hair cells.
In 2003 Yehoash Raphael of the University of Michigan Medical School at Ann Arbor and his colleagues had triggered inner ear hair cell growth in guinea pigs using adenoviruses that inserted a gene called Atoh1. Normally Atoh1 is active only during embryonic development in cells that go on to become hair cells. Expanding on these experiments, they reported the first instance of scientists restoring function to inner ear hair cells in live adult mammals.
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In March they published a study in which they employed their gene therapy on the left ears of 10 guinea pigs deafened by drugs. Eight weeks afterward the nonsensory cells lining the ears transformed into new inner ear hair cells and led to improved hearing. Raphael's group is not the only one working in this area.
Zheng-Yi Chen of Massachusetts General Hospital and his colleagues also found they could regenerate inner ear hair cells in mice. They started with a broad survey of gene expression patterns during embryonic development of the inner ear in mice and isolated a gene, Rb1, that appears to permanently brake hair cell growth. Their study, published in January, reported that deleting Rb1 led to mice with more apparently functional inner ear hair cells than normal. They also found that cultured mature inner ear hair cells from mice were able to regenerate when they had Rb1 knocked out.
Raphael and his team caution that they improved hearing but did not restore normal hearing and that it will take many years before Atoh1 gene therapy will prove ready for humans. Chen and his colleagues remarked that knocking out Rb1 made hair cells divide continuously, which could potentially lead to tumors. Future research should focus on inactivating Rb1 only long enough for clinical benefit.
As effective as gene therapy might prove in the future, the viruses that gene therapy often employ to carry genes into the body can sometimes kill a patient or cause cancer. Paras N. Prasad, executive director of the University of Buffalo Institute for Lasers, Photonics and Biophotonics, and his team are developing silica particles roughly 30 nanometers wide as nonviral vectors for carrying out gene therapy.
Organic molecules coating the nanoparticle surfaces bind to genetic payloads and protect the delicate DNA from enzymatic digestion. Prasad and his colleagues reported in July that when injected into mouse brains, the nanoparticles affected more than one third of targeted cells, with equal or greater effectiveness than existing viral delivery systems. No mice showed adverse side effects one month after the injections. Research on both new therapies and gene delivery methods point toward ways of overcoming the tremendous obstacles that this form of therapy has confronted.