Study Suggest Imaging Technology Could Measure Disease Severity in Friedreich Ataxia

Rare Daily Staff

A non-invasive eye exam that uses innovative imaging technology effectively measures the severity of disease in patients with the rare and progressive neuromuscular disease Friedreich ataxia, according to a new study.

Researchers at Weill Cornell Medicine, Weill Cornell Medicine-Qatar, and New York-Presbyterian published their findings in a study in the Annals of Neurology. The results suggest that the exam, known as corneal confocal microscopy (CCM), could be a rapid and sensitive tool for assessing patients in the clinic and the images could act as a biomarker in clinical trials testing new therapies for the disease.

Friedreich ataxia is an inherited genetic condition that causes increasingly impaired muscle coordination over time. People with the condition typically require a wheelchair about 10 years after signs and symptoms appear, and most die in their late 30s. The symptoms include the loss of coordination of gait, hand, and eye movements, slurred speech, uneven weakness in muscles of the limbs, sensory loss, wasting of the optic nerve, abnormal thickening of the heart muscle, and diabetes. The disease is diagnosed through clinical and neurologic evaluations, followed by genetic testing.

CCM produces high-resolution images of thin layers of corneal tissue, allowing investigators to measure nerve fiber density, length, and branch density. The test takes a few minutes and requires a couple of drops of anesthetic in each eye before the pictures are taken. By contrast, current clinical assessments involve a series of evaluations to assess muscle movement and neurological performance and take much longer to complete.

“The corneal nerves are a window into the health of the nervous system,” said senior author Ronald Crystal, chairman of the Department of Genetic Medicine at Weill Cornell Medicine.  Crystal is a paid consultant for Adverum, a biotechnology company that partially supported this study.

“The fact that our results align so well with the gold standard clinical evaluation tools, the Friedreich Ataxia Rating Scale (FARS) and the Scale for the Assessment and Rating of Ataxia (SARA) and the underlying genetics provides strong evidence that CCM is an efficient and accurate tool we should add to our diagnostic techniques,” he said.

For the study, researchers in New York and Qatar used the technology to examine the corneal nerves of 23 patients with Friedreich ataxia and 16 people without the disease. Patients with Friedreich ataxia had a significantly lower number of nerve fibers and shorter nerve lengths compared with people without the disorder.

The researchers compared the CCM test results with data from the current clinical assessment tools and genetic testing. The CCM results correlated with disease severity, age of disease onset and diagnosis, FARS and SARA scores, and genetic test results.

For six of the 23 patients with Friedreich ataxia who were still ambulatory, the CCM results also correlated with gait abnormalities observed in walking tests. The strong correlation with existing assessment tools suggests that CCM could act as an accurate biomarker for the disease.

The researchers believe using CCM as a biomarker for future clinical trials of experimental therapies for Friedreich ataxia could help identify responders more quickly, optimize doses, and save valuable time in the drug development process.

“As a rapid, non-invasive diagnostic test, CCM may serve as an effective therapeutic endpoint for measuring outcomes in future studies for Friedreich ataxia and potentially other neurological diseases such as Alzheimer’s disease,” said Crystal.

January 30, 2019

Photo: Ronald Crystal, chairman of the Department of Genetic Medicine at Weill Cornell Medicine.  Photo credit: Jesse Winter