ARTICLE IN BRIEF
Investigators are developing the prototype for a bio-nano-chip that uses saliva to check levels of antiepileptic drugs, providing a potential alternative to blood tests.
Epilepsy patients might one day be able to test their levels of antiepileptic drugs (AEDs) by placing a drop of saliva on a home monitoring device the size of a credit card.
Researchers in Houston at the University of Texas and Rice University are developing a bio-nano-chip (BNC) that uses saliva to check AED levels, providing a potential alternative to blood tests. While the device is still in the early phase of testing, the researchers presented preliminary data from their efforts at the American Epilepsy Society (AES) meeting in Washington, DC, last month.
“The idea is to have a monitoring system that is portable, inexpensive, able to be used multiple times, patient-operated, and non-invasive,” said Giridhar P. Kalamangalam, MD, DPhil, associate professor of neurology at University of Texas Health Science Center at Houston. “All it requires is a drop of spit.”
Dr. Kalamangalam, an epilepsy specialist, teamed up with John T. McDevitt, PhD, a professor of chemistry and bioengineering at Rice and a pioneer in “lab-on-a-chip” sensor technology, to see if it could be useful for epilepsy patients.
“Serial serum AED measurements can be crucial in managing a patient's dosing, however, it is impractical for serum levels to be monitored too frequently,” the study authors noted in their abstract for the meeting. “There is an urgent need for alternative AED assay technologies that are non-invasive, repeatable, adapted to domiciliary use, and cost effective.”
BNCs are likely to play an important role in medicine in coming years, for everything from cancer to heart disease to stroke. The compact chemical processors can be programmed to test for any number of biomarkers or drugs, conceivably providing a more convenient and less expensive alternative to laboratory testing.
Dr. Kalamangalam told Neurology Today that he thought the technology could be particularly useful for epilepsy patients who may be medically unstable or undergoing frequent dosage adjustments, or for those in resource-poor settings or without easy access to blood tests at a health care facility. Instead, “they can do it at home,” he said.
The abstract outlines the results of early testing of a BNC programmed to measure levels of two AEDs, phenytoin and phenobarbital. Epilepsy patients taking one or both of the drugs were recruited in an outpatient setting. Each volunteer provided a single serum sample and multiple saliva samples, collected by passive drool or obtained by oral swab.
The researchers then compared drug blood levels measured by the BNC to levels obtained through “gold standard” blood and saliva analyses. In their abstract, the researchers reported on eight sets of those results. [For the eight sets of measures, link to the abstract: http://bit.ly/1ex3e4P.]
“There seems to be a very good correlation between what the BNC and the gold standard tell us,” Dr. Kalamangalam said. His team is continuing to test the approach and plans to eventually report more details on their findings in a published paper. The research was funded by the John S. Dunn Foundation.
“We provide proof-of-concept for a realistic saliva-based BNC assay system for two commonly used AEDs, validating our results against gold standards,” the researchers concluded in the abstract. “Further work aims to produce a practical point-of-care diagnostic of this type — eventually a handheld sensor — for multiple AEDs that will empower patients to monitor their own drug levels in the community.”
Dr. Kalamangalam said that the device makes “long-term economic sense” because it allows patients to monitor their medication level — and make modest adjustments of drug dosages as needed at home — leading potentially to better seizure control and fewer expensive hospital or emergency room visits and lab tests.
Dr. Kalamangalam said that while the prototype device being tested checks for only two AEDs, the eventual goal is to have a device that would be programmed to simultaneously test saliva for levels of many different drugs. He said the plastic sensor card would be inserted into an electronic “reader” machine the size of an electronic pencil sharpener that then would read and display the results.
Epilepsy specialists not involved with the research said the technology under development, if proven to be reliable in further testing, could be useful in certain situations, in particular when patients are starting on an AED or having symptoms that might be related to the AED level. They cautioned, however, that there is a danger in placing too much emphasis on drug levels when treating epilepsy.
“I believe that for some patients this could be very useful,” said Frank Gilliam, MD, MPH, professor of neurology and neurosurgery at Penn State University. For instance, he said, a patient may want to check their drug level during a vulnerable time, such as during an infection or a period of sleep deprivation.
“They could check their level and make sure they are at a comfortable range for them,” Dr. Gilliam said. He said the bio-nano-chip could also provide an immediate drug-level reading after someone has a breakthrough seizure, information that could be useful in determining whether a dosing change is warranted.
But he said there are potential downsides as well to the technology. “Many physicians are conditioned to the idea that good management of epilepsy involves getting frequent blood levels. They make that part of every visit,” Dr. Gilliam said. “In my practice, I infrequently check blood levels.”
He relies on a clinical assessment, including using accurate screening instruments — monitoring whether there were any seizures since the last visit; drug side effects; or comorbid problems such as symptoms of depression — to determine if medication needs to be adjusted or other interventions are needed.
Nathan Fountain, MD, professor of neurology at University of Virginia, agreed that that blood level monitoring isn't necessary for the vast majority of patients. “We like to treat the patient not the blood level,” Dr. Fountain said, noting that an effective level for one person might not be for another.
He said that it was more common to check blood levels with older AEDs, such as phenytoin and phenobarbital, because they have a narrow therapeutic index and a small change in dose can result in side effects.
“The newer drugs tend to be more forgiving,” he said.
Edward Faught, MD, professor of neurology at Emory University, said he could see that the technology, if it's proven to be a valid assessment tool, could be helpful in some circumstances, such as when a patient's dose of a new medication is being adjusted. But he noted that that constant monitoring by a patient could cause confusion, in part, because blood levels can vary throughout the day, depending when a medication is taken. Patients could also become unnecessarily anxious about their readings if they vary from one measurement to the next.
“This could be overused,” Dr. Faught said. “Levels have limited usefulness,” when it comes to determining treatment.