Originally published April 13.
By Turna Ray
Chronix Biomedical is working with undisclosed pharmaceutical partners to apply its circulating DNA diagnostic methodology to personalize treatments for neurological disorders, the company said this week.
Chronix CEO Howard Urnovitz discussed the company's plans to develop and commercialize companion diagnostics with Pharmacogenomics Reporter last week, as a new paper published in the Journal of Molecular Diagnostics provided further evidence of the utility of Chronix's serum DNA blood test in diagnosing multiple sclerosis and predicting response to treatment. The company's testing platform uses sequencing and bioinformatics techniques to analyze circulating DNA in blood.
"We're in discussions with pharmaceutical companies, diagnostic companies, and governments to put together programs to start testing thousands of serum samples," Urnovitz said. Commercial development of companion tests will not begin until validating studies are complete and the data are published, he added.
In the study published in JMD, researchers from Chronix and several other institutions identified genomic DNA fingerprints in the bloodstream of 28 MS patients known to have relapsing or stable disease as compared to 50 healthy volunteers. Furthermore, these circulating DNA signatures were used by researchers to distinguish between MS patients and healthy volunteers, as well as differentiate periods of active disease attacks from periods of disease remission. This form of relapsing-remitting MS affects about 85 percent of patients.
"The focus of this paper is to show how … [one can] use this companion diagnostic test for personalized medicine," Urnovitz said. The study shows how "each person, while they have the same pattern of MS, have their own unique damage done. This can lead to better treatment options."
In the paper, the authors also asserted that the development of a serum-based diagnostic test for MS can reduce healthcare costs.
The researchers pointed out that the current method for monitoring MS status, magnetic resonance imaging with gadolinium dye, costs an average of $3,500 in the hospital setting, which limits the number of patients that can be recruited to randomized-controlled trials. "With the ever-increasing efforts to reduce the costs of medical care, serum-based assays (estimated to be $100 to $250) with appropriate validation could replace Gd-MRI as the primary standard for diagnosis as well as disease monitoring as a function of drug therapy," the researchers wrote in the paper. "The data further suggest that circulating nucleic acids in MS may provide additional tools to address pathogenesis."
Due to confidentiality agreements with Chronix's collaboration partners, Urnovitz could not discuss in detail the companion tests it is developing. However, in a statement announcing the publication of the JMD paper, Urnovitz said that the company is "now preparing to offer laboratory testing services to support clinical trials for new neurologic drugs," including MS, Alzheimer’s disease, amyotrophic lateral sclerosis, Parkinson’s disease, and autism.
The company said it will eventually launch testing services that will allow doctors to monitor ongoing disease status and response to treatment in patients with MS and other neurological diseases.
In the study published in JMD, researchers sequenced serum DNA from 28 patients with definite relapsing-remitting MS using mass sequence and assembly techniques, and diagnosed 13 patients as relapsing into MS. In these patients, blood was drawn within one week and before any treatment was given. The rest of the 15 patients, who were in remission, remained in this state for at least six months before their DNA was sampled.
[ pagebreak ]
"Of all nucleotides obtained from relapsing MS and stable MS patients, 82 percent produced significant hits on one of the public databases, of which greater than 99 percent aligned to the human genome," the researchers wrote in the paper. "The relative amount of genes, pseudogenes, transcribed, and untranslated regions (annotated as RNA and UTR) and coding sequences was calculated and compared with the relative amounts observed in the circulating DNA pool of control samples obtained from 50 apparently healthy individuals."
In comparing the expression of genes and repetitive elements in circulating DNA between MS patients and healthy controls, researchers confirmed that Hs17, a known MS locus, is significantly overrepresented "as a source of DNA motifs in relapsing MS patients …with three distinct chromosomal hot spots."
Additionally, a multivariate regression model using the single repetitive elements AT_rich, L1M5, Hs17, L1MD, satellite, HervK-int (endogenous retrovirus), and L1MA4, along with chromosome-specific nonrepetitive elements of chromosome Hs17, provided "highly significant differences that distinguish relapsing MS patients from healthy control subjects," the researchers reported.
“These positive data further validate the premise underlying the Chronix approach, showing that the many genetic anomalies associated with active and stable relapsing-remitting MS can be detected by analyzing DNA fragments circulating in the blood serum,” Mario Clerici, a coauthor in the study and the chair of Immunology at University of Milan's department of biomedical sciences and technologies, said in a statement. “The prognostic value achieved in this study supports the ability of this new approach to help manage relapsing-remitting multiple sclerosis, potentially offering clinicians a new tool to easily assess which MS treatment options are most effective for their patients, as well as providing critical information that will facilitate development of the next generation of MS therapeutics."
Clerici is a member of the Chronix Medical Advisory Board and has an equity position in the company.
The newly published MS data is a follow-up to Chronix's earlier efforts demonstrating the ability of DNA-based assays to diagnose mad cow disease and chronic wasting disease in live animals, conditions that are usually diagnosed after animals are dead via post-mortem biopsies.
The company also published data earlier this year on the utility of its serum DNA blood for early detection of breast cancer. And last year, the company published data showing that its analysis tools characterizing and categorizing circulating nucleic acid markers can detect the presence of certain diseases in blood samples months to years before clinical symptoms appear.
If ultimately, through its various collaborations with pharma companies, Chronix is able to develop a companion test to gauge drug response in MS, then the diagnostic would be taken through the FDA. According to Urnovitz, Chronix's partners would assist the company through the regulatory submission process for any companion test when the time comes.