Magazine article Clinical Psychiatry News

FDA Panel Blocks Urine Test for Alzheimer's: Test Detects Neural Thread Protein, but It's Unclear Whether That Is a Valid Biomarker of the Disease

Magazine article Clinical Psychiatry News

FDA Panel Blocks Urine Test for Alzheimer's: Test Detects Neural Thread Protein, but It's Unclear Whether That Is a Valid Biomarker of the Disease

Article excerpt

GAITHERSBURG, MD. -- A simple, nonnvasive urine test aimed at helping physicians determine whether a patient has Alzheimer's disease is unlikely to become widely available in the near future.

According to the manufacturer, what is under Food and Drug Administration review is the test kit, which has been approved in Europe. The actual test already is approved for sale in the United States, but it is only available through the manufacturer's lab. Approval of the kit would enable the company to provide it to other laboratories.

At a summer meeting of the FDA's Immunology Devices Panel, the majority of the panel agreed in a 5-2 vote that a urine test kit that detects neural thread protein (NTP), a protein that is present in Alzheimer's disease (AD) brain lesions, was "nonapprovable" for use as an aid to diagnosing AD. Concerns raised included whether the test was a valid biomarker for AD, whether the test result would have a positive impact on the diagnostic decision-making process, and uncertainty over whether it would be elevated in other neurodegenerative diseases.

Evidence suggests that NTP is "involved in neuronal sprouting, apoptosis, and cell death," and "is a marker for Alzheimer's disease," according to the manufacturer. New Jersey-based Nymox Pharmaceutical Corp. The company has proposed that the test kit be used to measure levels of NTP in urine samples of patients with cognitive complaints or other signs and symptoms of suspected AD.

The proposed label says that the results "are intended for use, in conjunction with, and not in lieu of, current standard diagnostic procedures, to aid the physician in the diagnosis of Definite Non-AD versus Probable AD, Possible AD or MCI [mild cognitive impairment]." Nymox CEO Paul Averback, M.D., emphasized that the test should not be considered a stand-alone diagnostic, but, rather, "a measurement that adds useful information" and "moves the diagnosis along." The FDA usually follows the recommendations of its advisory panels, which are not binding. A statement issued by Nymox after the panel's vote said the company would continue to pursue approval of the test kit and would work with the FDA to meet possible requirements for more data resulting from the panel's suggestions.

The panel's vote was based on the results of a prospective study of 200 patients presenting to one of nine cognitive/memory disorder centers for an evaluation by experts in AD and related cognitive disorders.

The aim of the study was to show that the NTP test had a high degree of correlation with the results of a comprehensive specialist exam using National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for diagnosing probable AD.

Patients had the urine NTP measurement and, based on a comprehensive evaluation that included a neurocognitive assessment, a Mini-Mental State Examination, and structural imaging with CT, MRI, or other scans, were classified as having probable AD, possible AD MCI, or definite non-AD.

Patients categorized as "definite non-AD" were determined to have conditions that included age-related memory decline, pseudodementia due to depression, and metabolic disorders. An elevated NTP was set at above 22 mcg/mL, with a normal level at 22 mcg/mL or less; the test was performed on a first morning urine sample.

Nearly 80% (156 patients) had probable AD, possible AD, or MCI and were lumped together in the category of "not definite non-AD" in the study. Of the 57 patients with probable AD, 51 had an elevated NTP level and 6 had a normal level. Of the 56 with possible AD, 21 had an elevated NTP level and 35 had a normal level. The 43 patients with MCI were split, with 22 having an elevated level and 21 having a normal level. Only 4 of the 44 patients with definite non-AD had an elevated NTP level.

The sensitivity of the test--the proportion of patients in the "not definite non-AD" category who had an elevated NTP measurement--was 60% (94 of 156 patients), according to the company's analysis of the results. …

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