NEW YORK (GenomeWeb) – Biotech start-up NanoSomix said this week that it plans to launch its exosome-based Alzheimer's assay this fall, targeting the product at academic and pharmaceutical researchers investigating the disease.
The assay isolates neuronal exosomes in patient blood and then measures their levels of the Alzheimer's biomarkers amyloid-β42 and phosphorylated tau protein. According to President and CEO John Osth, this approach lets the company measure patient biomarkers without needing to perform lumbar punctures to collect cerebrospinal fluid.
In a study published this month in Alzheimer's & Dementia, the company and collaborating researchers found that exosomal levels of two phospho-tau isoforms along with exosomal Aβ42 and total tau could classify 96 percent of Alzheimer's patients in a cohort of 57 cases and 57 matched controls.
The study also suggested the exosomal biomarkers might prove useful for identifying asymptomatic patients likely to progress to Alzheimer's, Osth said. For instance, a comparison of 29 amnestic mild cognitive impairment patients with 28 Alzheimer's patients with dementia found no difference in marker levels. Additionally, an analysis of 24 other Alzheimer's patients found that elevated phospho-tau levels were detectable in cognitively normal subjects up to 10 years before their Alzheimer's diagnosis.
Larger studies will be needed to confirm these findings, Osth said, noting that the company has run around 500 patient samples to date.
"We're developing a pretty good database, but we have to go a lot further," he said, adding that NanoSomix currently has studies underway with several outside researchers, including a project looking at the markers for differential diagnosis of various dementias and a longitudinal study further exploring their usefulness for early detection of the disease.
Ultimately, Osth told ProteoMonitor, the goal is to develop companion diagnostics for use by pharmaceutical companies in selecting subjects for their clinical trials and, eventually, for identifying patients likely to benefit from a particular therapy.
According to a theory shared widely by researchers and clinicians, Alzheimer's drug development has proven challenging in large part due to the difficulty of identifying and enrolling patients early enough in the disease process for drugs to have a significant effect.
Typically, Alzheimer's drug trials are done in patients who have already developed dementia, meaning that their brains are likely already so damaged that it's difficult to determine the benefit, if any, of treatment.
This problem has fostered much interest in biomarkers for early detection of the disease, the thinking being that if patients are enrolled earlier, drugs might have a better chance of working. Much Alzheimer's protein biomarker research has revolved around CSF levels of Aβ and tau. However, because many patients – and especially asymptomatic ones – are hesitant to undergo a lumbar puncture, the field is interested in identifying plasma-based markers.
Indeed, a number of academic, government, and industry groups are investigating plasma protein markers for the disease. In 2013, for instance, molecular neuropsychiatry firm Genomind signed an exclusive licensing agreement with Emory University to commercialize blood-based protein markers for the disease that stemmed from a 2012 analysis of potential plasma protein in three separate patient cohorts done by a consortium of researchers under the Alzheimer's Disease Neuroimaging Initiative.
In July, a team led by researchers from King's College London and Proteome Sciences identified a panel of 10 protein biomarkers that could help predict patients likely to progress from mild cognitive impairment to Alzheimer's.
The search for plasma markers, however, presents potential sensitivity issues, as neuronal proteins may be present in the blood only in small amounts given that they must pass through the blood-brain barrier. In the case of phospho-tau, Osth said, the protein phosphorylations are often removed by phosphatases once the protein crosses over into the bloodstream, making it difficult to measure reproducibly in plasma.
This, he notes, is where NanoSomix's exosome-based approach offers a potential advantage. Employing methods developed by company Co-founder and former Hitachi Chemical researcher Masato Mitsuhashi, company researchers are able to capture and isolate neuronal exosomes in plasma using CD171 antibodies. They then lyse them and measure the Alzheimer's markers inside, the idea being that the contents of these neuronal exosomes offer a measure of the levels of the target markers in the brain.
Osth declined to describe this isolation process in detail, but, he said, the ability to reproducibly and in high-throughput capture these neuronal exosomes and measure the proteins inside is at the root of the company's strategic advantage. He added that NanoSomix has filed several patents on the approach.
The company plans this fall to launch research assays for exosomal phospho-tau, tau, and Aβ42 with the aim of developing collaborations in academia and pharma to collect additional data on the markers and their performance for detection of Alzheimer's, Osth said.
He noted as well that in the future the company plans to investigate other potential neuronal exosome markers for conditions like traumatic brain injury and other dementias. Further down the road, Osth added, NanoSomix could turn its technology to looking for markers in other tissue-specific exosomes.
"One specific example is exosomes coming from stem cells in the bone marrow," he said. "You can pull out those stem cells, but it's hard, and you have to administer drugs to get a lot of them. The [stem cell] exosomes, though, are coming out at will. So you can collect the exosomes and measure what's inside the exosomes far more easily than you can collect the stem cells."
In addition to Osth and Mitsuhashi, NanoSomix counts as a Co-founder Edward Goetzl, a senior investigator at the National Institute on Aging. The company currently has five employees, Osth said, and is operating under angel funding, with the three co-founders each among its largest investors.
NanoSomix is planning a Series A financing round for sometime around the end of the year, he said.