By Forest Ray
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NEW YORK – Precision medicine company AMPEL BioSolutions and academic partners at Duke University identified two distinct gene signatures for systemic lupus erythematosus (SLE), one of which appears specific to patients experiencing fibromyalgia.
If validated, these signatures could be used to confirm diagnoses and inform new treatment strategies. The fibromyalgia signature in particular will form the basis of the company’s FibroGene blood test, expected to launch next year.
“A lot of progress has been made in inflammatory lupus, but the majority of patients experience fibromyalgia-like symptoms, such as brain fog and fatigue,” said Amrie Grammer, AMPEL’s founder, president, and CSO.
Grammer added that because of our limited understanding of fibromyalgia’s biological mechanisms and the resulting lack of medications specific for treating it, the National Fibromyalgia Association refers to the disorder as an “invisible disability.”
AMPEL’s study was published in Lupus Science & Medicine and used whole-transcriptome sequencing to compare the differences in gene signatures between molecular endotypes of SLE among 18 patients with or without co-occurrence of fibromyalgia symptoms, dubbed SLE type 1 and SLE type 2, respectively.
RNA was isolated from blood samples and sequenced on the Illumina HiSeq platform. Gene expression patterns seen in type 1 patients largely associated with type I interferon and neutrophils, while B cell-associated signals and neuromuscular pathways were more prominent among type 2 patients.
The researchers, led by AMPEL and collaborating with the lab of Duke’s David Pisetsky, a professor of medicine and immunology, also examined gene expression data from fibromyalgia patients without SLE via the company’s machine learning-driven AMPEL Genomic Platform (AGP).
Amrie explained that AGP identifies groups of correlated genes and that it has identified approximately 200 groups that the company claims define all immune and inflammation-related pathways. She said that AMPEL must still go through validation studies to identify exactly how many groups will be included in FibroGene.
The researchers found certain molecular signals characteristic of symptoms associated with each SLE subtype.
“The fibromyalgia aspect of lupus looks pretty similar to straight up fibromyalgia,” Grammer said adding that the results, particularly with respect to type 2 SLE, “look like fibromyalgia embedded within lupus because the signatures are the same.
Mary Crow, chair of immunology and inflammation research at Weill Cornel Medical College’s Hospital for Special Surgery, described the study as “provocative,” saying that it provides opportunities to better characterize the underlying biology of SLE and to gain insight into the pathophysiology underlying those patients with fibromyalgia.
Nonetheless, she cautioned that the study’s small size makes further experimentation crucial.
“It will be important to replicate the results in other patient groups,” she said.
Examining mixed symptom cases, as opposed to individuals presenting with largely type 1 or type 2 clinical SLE features, will provide further insights into SLE and fibromyalgia pathophysiology, she explained. How the expression signatures identified in this study change over time will also be important to understand, particularly as the study suggests that the clinical picture in a particular lupus patient can transition between endotypes.
Crow added, though, that the results coming from the fibromyalgia patients are particularly interesting because those symptoms can be so difficult to treat effectively.
“Defining subgroups of fibromyalgia patients based on their gene expression transcript profiles may provide new understanding of the basis of their pain and fatigue and may suggest therapeutic options for those patients,” she said.
AMPEL is now planning a larger study with the goal of obtaining CLIA validation for FibroGene through ResearchDx, a CLIA-certified lab in Irvine California, in the first half of next year.
The company also plans to roll out tests for several other indications over the next three years.
The first test in the pipeline is LuGene, a blood test for type 1 SLE, expected later this year. DermaGene, a skin biopsy test for lupus, psoriasis, atopic dermatitis, and scleroderma, is planned for May of 2024; and WellGene, an inflammation blood test, is planned for later that same year. Similar to FibroGene, these tests also aim to help diagnose their related conditions via gene expression analysis.
All tests consist essentially of sample acquisition, sequencing, and RNA analysis, and Amrie noted that the tests are agnostic to which sequencing platform is used.
AMPEL released early-access versions of both LuGene and DermaGene last year.