Four scientists at Rocky Mountain Laboratory in Hamilton and several of their Italian colleagues from the Neurosciences Department, Biomedicine in Verona University, the Cellular Biology and Neurosciences Department of the National Institutes of Health in Rome, and the G.B. Rossi Hospital in Verona were all recipients of the 2019 Aspen Institute Italia Award for scientific research and collaboration between Italy and the United States.
Established in 2016, this annual award honors a research contribution in the theoretical or applied natural sciences which is the product of collaboration between scientists and/or research organizations in Italy and the United States. The aim of the Award is to raise the profile of collaborative efforts between Italy and the United States in the field of scientific research in the natural sciences and its associated applications.
According to a press release from the Aspen Italia Institute, the team of scientists received the award in recognition for their collaborative effort in developing a test for Creutzfeldt-Jakob Disease (CJD) using nasal brushings, stating, “Their research represents a significant step forward in diagnosing prion diseases and opens a new and broad perspective of diagnosis in the field of those neurodegenerative diseases that are more common and that have a significant social and economic impact.” The award was presented to the scientists at the institute headquarters in Italy on October 23.
The originality of the research lies in having devised a simple and non-invasive procedure for the reliable diagnosis of prion diseases. The neurons of the olfactory mucosa are taken with nasal brushing and then analyzed with a new technique that amplifies prions in vitro, called “real-time quaking-induced conversion (RT-QuIC).” This test is highly innovative
because it combines the high sensitivity of the RT-QuIC technique (used to identify the pathogenetic marker of prion diseases) with a non-invasive collection technique that can be used on living patients.
International criteria require that the definitive diagnosis of prion disease be obtained exclusively by a biochemical or histological exam. Indeed, before the research being recognized here was undertaken and proved successful, a certain diagnosis of prion disease could only be obtained after death, with a brain autopsy. A biopsy of a living brain is never recommended because of the high risk of contamination and the high costs of sterilizing healthcare facilities.
“Having a test capable of making a definite diagnosis of prion disease while a patient is still alive, therefore, is an extremely important step forward in our understanding of these diseases,” states the Institute, “It informs family members, avoids further tests, reduces costs and allows timely treatment.”
In the near future, the diagnostic use of nasal brushing coupled with the RT-QuIC technique could be extended to other neurodegenerative diseases (such as Parkinsonʹs, Alzheimerʹs and Lewy Body Dementia). RT-QuIC performed on samples of olfactory epithelium could identify the marker proteins of these diseases, thereby allowing diagnoses even in very early stages of the disease. In most neurodegenerative diseases – in particular Parkinsonʹs – the first neuropathological lesions are observed in the olfactory system; indeed, olfactory disorders represent a very early non-motor symptom of the disease.
Dr. Byron Caughey, the lead investigator at RML’s Laboratory of Persistent Viral Diseases, said that it was Dr. Gianluigi Zanusso at Verona University who set the research in motion. He said it was Dr. Zanusso who recognized that CJD patients had pathological protein deposits in lesions in the upper regions of their nasal cavities. When he learned about the research being done here by Dr. Christina Orru (who works at RML but received her education in Italy at Verona University), specifically her work on identifying a corrupted protein associated with prion disease, he called Dr. Caughey.
He asked whether, if he sent a nasal swab in a sealed test tube, the lab could test for prion seeding activity. Dr. Caughey said yes, even though it was Dr. Urro who would primarily conduct the “real-time quaking-induced conversion (RT-QuIC)” tests.
Dr. Caughey said the lab performed the tests blind. The samples included many patients suffering from CJD and some from healthy people. He said the RT-QuIC test identified 97% of the CJD patients and did not identify any of the non-CJD samples as positive.
Caughey said that Orru and the team at RML have already had success with a test using samples of spinal fluid. But that procedure involves a lumbar puncture, that is a needle into the spinal canal. Sometimes that procedure is not possible, he said, or the patient refuses it. He said that the nasal swab has shown itself to be an effective test on its own and can now be used as a back-up.
“It’s really nice to have back-ups,” said Caughey, “when you do a test and you are about to tell a person that they have a horrible, fatal, untreatable and rapidly progressing neurological disease it’s nice to have further confirmation.” The lab can now issue a certified diagnosis of CJD to a patient who samples test positive and be close to 100% certain, he said.
“A decade ago we couldn’t diagnose CJD at all except post-mortem,” he said.
Caughey said that the work toward developing tests applicable to Alzheimers, Parkinsons and other diseases is ongoing, and they were “having considerable success.”
He said that being able to identify particular diseases in living patients as well as identify people who are not helps researchers tremendously in setting up clinical experiments. He said the lab was also looking at groups of people who have a certain gene mutation that renders them likely to develop CJD in their lifetime. Studying the disease in its early stages of development, before any symptoms present could present a better opportunity for successful therapeutics.
Currently in the U.S. alone there are 5 to 6 million people with Alzheimer’s Disease. This is expected to rise to 14 to 15 million in the U.S. alone over the next 30 years. The cost of dealing with it has been estimated at $1 trillion.
Dr. Orru has already trained people at 30 different laboratories around the world how to perform these tests. She and Dr. Andy Hughson have also just finished a blind examination of 200 samples testing for Parkinsons disease and performed well. They also performed well on a large set from Sweden.
“We are doing these tests on multiple fronts,” said Orru. The aim is to produce a battery of tests for all the major neurodegenerative diseases and get people trained around the world to conduct the tests.