Johns Hopkins physicians report success in a small study of a modified skin biopsy that hastens the earlier diagnosis of an inherited and progressively fatal nerve disease and seems to offer a clearer view of the disorder’s severity and progression. With a quicker and less invasive way to visualize the hallmark protein clumps of the rare but lethal disease – familial transthyretin amyloidosis – the researchers say they hope to more rapidly advance clinical trials of treatments that may slow the disease and extend patients’ lives.

In a report on their study, published June 20 in the journal Annals of Neurology, the Johns Hopkins team found that increasing levels of the protein clumps corresponded with worsening nerve damage, indicating that the smaller skin biopsies they used appear to work well as a measure of disease severity.

For the study, his group recruited 30 patients with six different genetically–confirmed transthyretin amyloidosis mutations. Twenty patients had neuropathy symptoms and 10 did not. They also recruited 20 age and gender–matched healthy controls, and 20 age and gender–matched patients with diabetic neuropathy – a different form of peripheral nerve damage due to high blood sugar. Participants ranged in age from 17 to 83; 42 percent were women.

Each subject had skin biopsies taken from their outer ankle and upper thigh. The biopsies were thinly sliced and stained with a dye called Congo red that allowed the researchers to view the protein clumps in the layers of skin or within the sweat glands and pilomotor muscles (those that cause goose bumps) under the microscope. These red protein clumps looked yellowish–green when observed with a polarized lens distinguishing them from other structures in the skin sample.

Researchers observed the protein clumps in 14 people with symptoms of neuropathy and the disease and in two people with the disease but without accompanying neuropathy symptoms. The protein clumps weren’t seen in any of the healthy controls or in samples from people with diabetic neuropathy.

Based on their results, Gigi Ebenezer, MBBS, MD, assistant professor of neurology and the first author on the study, reported that protein clumps were detected in 70 percent of cases and 20 percent of patients who carried disease–causing genes but hadn’t yet developed symptoms. None of the control cases showed amyloid.

“But if further studies confirm and extend what we have found, we may use the skin biopsy as a biomarker for disease severity. And we will be able to diagnose more patients sooner, which is important for patients and their families so they can begin planning for the future,” says Polydefkis. “The good news is that drug companies are using our skin biopsy technique in ongoing clinical trials to monitor treatment success.” He says results from phase II and III trials on these new therapies designed to stall the disease are slated to come out within the year.