A recent multicenter trial shows a natural factor that encourages nerve growth may bring relief from one of the more common effects of HIV infection: sensory neuropathy. The study, led by Johns Hopkins researchers, is supported by the AIDS Clinical Trials Group at the National Institutes of Health.
While not life-threatening, sensory neuropathy brings misery to thousands of HIV patients by producing burning, aching or tingling feelings as a result of injury to small sensation-bearing nerves. The injury comes from either the viral infection itself or the toxic effects of specific antiviral treatments. "Nearly a third of people with AIDS have these neuropathies, most often affecting the legs and feet," says neurologist Justin McArthur, MBBS, M.P.H., "Patients may be in constant pain and many have difficulty walking. It's quite a problem."
This spring, McArthur and a research team reported on a multicenter trial of 271 patients with HIV-related sensory neuropathy to evaluate genetically engineered nerve growth factor as a treatment. Nerve growth factor (NGF), found naturally in the body, is a small, potent molecule that helps maintain certain nerve cells. It also prods those nerve cells to grow and to communicate with other cells.
In the study, presented at this year's International AIDS Conference in Geneva, the patients got injections of either a moderate dose of lab-created NGF, a higher dose or a placebo. Throughout the 18-week trial, the team asked patients about improvements, had them rate their pain and took other neurological measures. The result, says McArthur, was that "patients said the intensity of pain was significantly lessened, and neurological exams showed improved sensation."
One offshoot of the study is that the researchers have verified precisely which nerves are involved in the injury -- something not done before. With a punch biopsy, a relatively painless technique little-used in neurology but common in dermatology, they removed small samples of the outer layers of skin. Under the microscope, the researchers found far fewer of the tiniest sensory nerves in the epidermis than normal. "We suspect other, larger nerves are recruited to take over the missing function," says John Griffin, M.D., head of neurology at Johns Hopkins. Those nerves are somehow more prone to produce pain.
As for the next step -- seeing if NGF triggers regrowth of patients' nerves -- that's under way, the researchers say. "For now," says McArthur, "we can measure the damage and treat the symptoms."
Currently, no existing treatment for HIV-related sensory neuropathy stops its degenerative path. Therapy has been limited to treating the pain by combining drugs such as tricyclic antidepressants, anti convulsants and/or painkillers, and using common-sense approaches like avoiding tight shoes.
Co-researchers on the study were Constantin Yiannoutsos of Harvard University, David Clifford of Washington University in St. Louis, Giovanni Schiffito of the University of Rochester, Betsy Smith of the NIAID, David Simpson at Mt. Sinai Hospital in New York City and research teams at 17 sites across the country.
The study was funded by grants from the National Institute of Neurological Disorders and Stroke (for grantholder David Clifford, M.D.) and by the National Institute of Allergy and Infectious Disease. It is under review for publication.
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