【News】Alzheimer's disease detection will be accelerated in 2021, and the technology will become more market-oriented

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Author: John

The diagnosis of Alzheimer's disease (AD) is more commercialized in 2021, with some developers announcing their intention to obtain regulatory licensing for their diagnostic products, while others have formed partnerships or received funding to support technology development. Among them, the FDA accelerated the approval of the Bojian biomonab drug Aducanumab for the treatment of Alzheimer's disease in June, and as the first AD approved drug, it undoubtedly directly promoted market confidence.

The U.S. Food and Drug Administration (FDA) approved aducanumab (Bojian's Aduhelm) as a β amyloid-targeted antibody to treat Alzheimer's disease in June, making it the first Alzheimer's drug to receive such approval in nearly 20 years. Although opponents of the approval say there is not enough evidence to suggest that the drug has any benefit for patients, some IVD developers see it as an important approval that has the potential to increase the need for (AD) testing.

A Fujirebio company based in Malvern, Pennsylvania, is seeking FDA approval for its Lumipulse Gβ-amyloid ratio (1-42/1-40) Alzheimer's in vitro diagnostic test, which runs on its fully automated Lumipulse G1200 immunoassay analyzer.

Hiroshi Sekiya, senior manager of product and account management at Fujirebio, said the FDA's approval of Fujirebio's test will mean clinicians who want to prescribe Bojian AD drugs can use the test to identify suitable patients. The assay is used to quantitatively detect concentrations of β-amyloid (1-42) and β-amyloid (1-40) peptides in human cerebrospinal fluid (CSF) and provides a numerical ratio that can be used to distinguish between Alzheimer's (AD) and non-Alzheimer degenerative dementia (NADD). The company received the EU CE marking for the test in 2017 and said it conducts more than 50,000 tests a year in memory clinics associated with European and other regulated hospitals.

In addition, Roche CEO Severin Schwan said on a July conference call that the company was also seeking FDA approval for its immune tests for diagnosing Alzheimer's disease. One of its tests measures the concentration of β-amyloid peptide, while the other measures the concentration of phosphorylated tau protein (phospho-tau) peptide in cerebrospinal fluid. Roche received "Breakthrough Equipment" certification for the test in 2018 and has been approved for use outside the United States.

In terms of instrumentation, the FDA awarded Quanterix's blood test Simoa phospho-Tau 181 (pTau-181) breakthrough medical device designation in October, a semi-quantitative immunoassay designed to measure pTau-181 concentrations in human serum and plasma using the Quanterix HD-X immunoassay system. Recommended indications include the use of test results in adult patients over the age of 50 to help aid in the diagnosis of Alzheimer's disease (AD).

Other companies are also working on the route of laboratory-developed tests (LDT), such as Alzheimer's testing company C2N Diagnostics, which continues to build cases for PrecivityAD, a highly sensitive blood test using mass spectrometry, to measure blood levels of amyloid (Aβ) 40, Aβ42 and apolipoprotein E. The test, which was launched as an LLT in October 2020, also takes into account the age of the patient and yields a score of 0 to 100, with higher scores indicating the greater likelihood of developing amyloid plaques of the brain characteristic of Alzheimer's disease.

In May, C2N Diagnostics and collaborators published a study in the journal Molecular Neurodegeneration that looked at test performance in 414 plasma samples collected from 6 different US cohorts (populations) and predicted amyloid status with 86 percent accuracy when the copy number and age of ApoE4 were included in the test model.

The St. Louis-based company and its collaborators published a separate study in clinica Chimica Acta that found that the assay has a level of precision, accuracy, sensitivity, and linearity appropriate for clinical testing. In addition, Amprion, a San Francisco-based biomarker testing company, announced the launch of SynTap Biomarker LDT at its CLIA facility in San Diego. It detects a-synuclein aggregates, which are markers of various brain disorders, and helps diagnose synucleosis such as Parkinson's disease, Lewy body dementia, and multisystem atrophy. It also helps distinguish between underlying synucleinopathies in other neurodegenerative diseases, such as Alzheimer's.

In other important studies in the field of Alzheimer's testing in 2021, in June, a team of researchers led by researchers at Lund University and the University of Gothenburg reported findings about the potential application of neurofilamental beam light (NfL) chains in the diagnosis and management of a range of neurodegenerative diseases. The researchers said the increase in NfL in Alzheimer's disease patients was fairly mild, and markers such as phosphorylated tau protein may be more effective in diagnosing the disease. On the other hand, they noted that elevated NfL levels may indicate non-Alzheimer's dementia in the absence of elevated phosphorylated tau proteins.

Many companies have announced progress in the development of technology for Alzheimer's diagnostic tests. Norwegian startup Pre Diagnostics says it is developing a monocyte blood immunoassay that can analyze the inside of innate immune cells to detect before Alzheimer's symptoms appear. The assay, known as PreADx, uses intracellular measurements to monitor clearance of amyloid β plaques in the brain, a hallmark of Alzheimer's pathology.

In addition, Biological Dynamics, a liquid biopsy company in San Diego, has been exploring a new AC electrodynamics-based system called Verita as a number of potential diagnostic applications, including the detection of Alzheimer's disease.

In terms of funding, South Korean diagnostics firm Speclipse announced in August that it had raised $7.7 million to develop additional applications for its laser spectroscopy technology, which has been used to diagnose skin cancer from tissues. The company is using artificial intelligence and deep learning to process and analyze vast amounts of spectral data from the bloodstream to enable early diagnosis of stomach cancer and Alzheimer's disease.

Synaps Dx, developer of neurodegenerative disease testing, announced in October that it had completed a $10 million Series A funding round. The Rockville, Maryland-based company, which operates a CLIA-accredited laboratory, is using the proceeds to scale up production and meet market demand for Discern, a minimally invasive test used to diagnose Alzheimer's disease and differentiate other forms of dementia. According to the company's website, Discern detected Alzheimer's disease in the earliest stages of onset by testing for the presence of biomarkers specific to three undisclosed diseases. In 2018, the company received the FDA's "Breakthrough Equipment" certification.

The neurodegenerative disease diagnostics company Valted Seq announced in November that it had received $10.5 million in seed funding, and the Maryland-based Gaithersburg company has been developing a platform called HiF-Seq to collect single-cell sequencing data from the postmortem brains of patients with neurodegenerative diseases such as Parkinson's and Alzheimer's. Valted Seq announced in April that it had received an exclusive license from Johns Hopkins University to evaluate biomarker analysis to diagnose and manage neurodegenerative diseases.

In addition, Circular Genomics, based in Albuquerque, New Mexico, announced in December that it had raised $4.5 million in seed funding to develop molecular diagnostic tests for depression based on the University of New Mexico's circulating RNA biomarker technology. Circle, which was founded earlier this year, also plans to develop Alzheimer's disease detection and predictive analysis, as well as tests for post-traumatic stress disorder and bipolar disorder.

Tataa Biocenter said in February that it had acquired a majority stake in Swedish genetic testing provider Life Genomics. Life Genomics was spun off from Gothenburg-based Tataa in 2014 to provide Alzheimer's risk tests as well as non-invasive prenatal tests for Roche Harmony chromosome abnormalities.

Among the companies working with Alzheimer's testing in 2021, Yourgene said in March that it had signed a contract with UK-based Cytox to run the company's genetic tests at Citylab1.0 lab in Manchester to predict the risk of Alzheimer's. The two companies previously signed a cooperation agreement and completed array-based inspection tests.

Cytox's GenoScore technology predicts the risk of cognitive decline caused by Alzheimer's disease by using a patient's saliva or blood sample. The technology, which runs on Thermo Fisher Scientific's GeneTitan instrument, analyzes more than 100,000 genes in patients. SNPs are associated with Alzheimer's disease, producing patient-specific polygenic risk scores. In February, Cytox obtained the CE marking for the GenoScore-Lab Alzheimer's disease genetic risk test and launched the test in Europe. Subsequently, the company said in June that it was working with Infinity BiologiX to launch an Alzheimer's disease risk test in the U.S. based on liquid biopsy, which uses Cytox's GenoScore platform. IBX, based in Piscataway, New Jersey, provides laboratories from its CLIA-accredited, CAP-accredited laboratories to develop tests.

In May, biopharmaceutical company Alzheon announced that it had entered into a cooperation and licensing agreement with the Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences to develop a detection method for Alzheimer's disease. Clinical trials are being developed to measure neurotoxicity in human cerebrospinal fluid β amyloid oligomers and address the limitations of the current detection of amyloid oligomers, methods that cannot distinguish individual species of amyloid oligomers.