A protein called alpha-synuclein that accumulates and ravages the brains of some people with Parkinson’s disease is the target of several experimental drugs. Until recently, the only way to detect it was by opening someone’s brain when they died.
That’s starting to change. Amprion, a 30-person biotech based in San Diego, has developed a way to detect small amounts of alpha-synuclein from spinal fluid. A study published last year in The Lancet Neurology suggests the method could help confirm suspected diagnoses and even predict Parkinson’s before common symptoms arise. And now Amprion is scaling up to commercialize the test.
CEO and co-founder Russell Lebovitz told Endpoints News in an exclusive interview that Amprion has raised $6 million in the first portion of its Series B, which will help it hire 15 more employees and expand its salesforce and operations throughout the US. The round was led by Formation Venture Engineering, with participation from Eli Lilly.
Lilly’s interest is notable because the pharma company helped pioneer the use of diagnostics to detect amyloid in the brains of people with Alzheimer’s disease. The drugmaker is also developing drugs for Parkinson’s, and the company’s scientific leaders have mentioned alpha-synuclein as an area of interest for future neurodegenerative research at the company.
“They have recognized, as have a lot of the drug companies, that this is going to be important in the future,” Lebovitz said.
Mad cow origins
The technology underlying Amprion’s test was forged in the early 2000s in the aftermath of the mad cow disease crisis.
Claudio Soto, a biochemist and professor of neurology at the UTHealth Houston McGovern Medical School, developed a way to detect prions, the misfolded proteins that cause bovine spongiform encephalopathy in cattle and Creutzfeldt-Jakob disease in humans. The infectious proteins cause natural versions of the proteins to misfold, leaving tainted and toxic prions in their wake as they spread through the brain.
That natural amplification formed the basis of Soto’s test. He added highly purified and properly folded proteins to spinal fluid or blood from a patient suspected of having the disease. If prions were present in the sample, they would quickly convert the normal proteins into diseased ones. He compared the method to PCR, the technique used to make many copies of DNA for easier sequencing.
Soto formed a startup with Lebovitz in 2007 that aimed to refine the technique, now dubbed a seed amplification assay. The mad cow crisis abated, but the duo believed the technique would be valuable to help detect other misfolded proteins, such as amyloid and tau in Alzheimer’s and alpha-synuclein in Parkinson’s.
The first 10 years were slow going. The test originally took nearly two weeks to run, but they got it down to 20 hours. And a fluorescent dye that only lights up in the presence of misfolded proteins made the results easy to interpret.
The tests are currently run out of its CLIA-certified lab in San Diego. The company is developing a simplified kit of the test that other labs can run, and hopes to submit it to the FDA in about 18 months.
By 2019, Amprion had developed an alpha-synuclein test for Parkinson’s that it believed would be scalable. The company raised a $13.7 million Series A over the next three years and began offering the test to doctors at major medical centers and research institutions in 2023, Lebovitz said.
The study published last year revealed that the test had a sensitivity of about 88%, meaning that about 12 in 100 people with Parkinson’s had a false negative result. Among the 1,100 healthy volunteers, the test had a 97% specificity, meaning about 3 in 100 people without the disease had a false positive. The test performed more poorly for certain subsets of Parkinson’s disease, including those with mutations in the LRRK2 gene linked to the disease.
New questions about alpha-synuclein
Drugmakers and regulators alike are increasingly turning to biomarkers to decide which patients to include in a clinical trial and how to assess whether the drug is working. In August, the FDA issued a letter of support encouraging “further study and use of” seed amplification assays for alpha-synuclein.
Amprion has worked on similar amplification assays for amyloid and tau, but these tests are still experimental. The company offers clinical tests for amyloid, tau and another brain biomarker called neurofilament using machines sold by Fujirebio.
With the new funding, Lebovitz said “we can hit every major medical center doing cognitive and motor disorders in the US.” He’s hoping to raise another $9 million in the Series B round this year to help the company open a lab in Europe.
But Amprion’s efforts to scale up come at a challenging time. About two weeks ago, an investigation published in Science cast doubt on several research papers supporting the role of alpha-synuclein in Parkinson’s disease.
More than 130 papers published by National Institutes of Health neuroscientist Eliezer Masliah had “suspect images,” including doctored and duplicated results, according to the report. Some of the questionable studies were cited as evidence underpinning the alpha-synuclein-targeting antibody prasinezumab, which is being developed by Prothena and Roche.
Lebovitz said that other scientists have consistently demonstrated alpha-synuclein’s role in Parkinson’s and other neurodegenerative diseases irrespective of Masliah’s studies.
“None of Amprion’s data relies on any work ever performed or published by Eliezer Masliah,” Lebovitz said. “We have never met with Dr. Masliah, and he has never provided any advice or other counsel.”