NEW YORK – Precision medicine company Ampel BioSolutions is developing a gene expression test that can predict kidney damage in patients with chronic kidney conditions such as lupus nephritis (LN).
Charlottesville, Virginia-based Ampel is developing the test, called NephroGene, using its Ampel Genomic Platform technology that uses bioinformatics and machine learning to analyze gene expression from microarray or RNA-seq data.
According to the company, the test identifies molecular markers in kidney biopsy samples of LN patients, which can help reveal patients' disease stage. This information, in turn, could help those pharmaceutical companies who have more than 45 LN drugs in development enroll patients in clinical trials with greater precision, Ampel said.
The company expects to bring this test to market in 2025 for LN diagnosis in patients and for pharma companies to identify the right patient population for LN drug trials. In the meantime, the company will offer the test to pharma companies for research.
Amrie Grammer, Ampel's cofounder, president, and CSO, believes the test could also be a game changer in the way doctors prescribe drugs for kidney diseases and shortlist patients for kidney drug clinical trials.
"Ampel's kidney tests are specifically based on the molecular pathways that are abnormal in the kidney biopsy," she added.
While the current standard of care for diagnosing LN is by doing a biopsy, which is viewed under a microscope for kidney damage, Ampel's LN test may be able to diagnose the disease well before damage occurs, the company said.
The foundational research for NephroGene came from a study of mice with LN that was conducted by Ampel along with scientists at the University of Virginia and Virginia Tech. The findings were published in Frontiers in Immunology last month.
For the study, researchers classified the mice kidneys into various disease stages by histological comparison, matching mice by level of disease pathology and amount of immune complex (IC) deposition.
RNA analysis of kidney samples from each stage revealed distinct immune profiles, according to the study's authors. For instance, there were distinct molecular profiles for acute disease; the stage after initial immune complex (IC) deposition in the kidney glomerulus; transitional disease in which inflammatory cell and pathway enrichment is at its peak; and chronic disease.
Next, they compared the gene expression profiles of human LN with those in mice LN samples and comparable stages of LN progression. The gene expression profiles of human LN were similar to those noted in mice with LN, suggesting comparable stages of disease progression.
George Tsokos, a professor of medicine specializing in rheumatology at the Beth Israel Deaconess Medical Center, told GenomeWeb that most LN patients show up in the clinics when their kidneys are already considerably damaged. At that stage, he said that treatments are limited, and, in some cases, the only options are dialysis or a kidney transplant. "Till now we have had no tools to identify patients at the earliest stages of LN," said Tsokos.
According to him, Ampel's study puts forth a concept that LN can be caught at an earlier stage, before the kidney damage begins, and that could have implications on its treatment.
"Ampel's work connecting mouse and human gene expression has clarified that there are initial acute and transitional stages of lupus nephritis that may be reversible with targeted intervention," he said in a statement.
The US Centers for Disease Control and Prevention states that half of patients with lupus — a condition in which the body's immune system attacks its own tissues — suffer from LN, with symptoms such as weight gain, swollen ankles, high blood pressure, and decreased kidney function.
Meanwhile, Ampel is developing tests for lupus in other organs, as well.
Earlier this year, the company had identified two distinct gene signatures for systemic lupus erythematosus (SLE), one of which appears specific to patients experiencing fibromyalgia.
The company also plans to roll out tests for several other indications over the next three years, including LuGene, a blood test for type 1 SLE, which is expected for later this year. Meanwhile, DermaGene, a skin biopsy test for lupus, psoriasis, atopic dermatitis, and scleroderma, is planned for May 2024; and WellGene, an inflammation blood test, is planned for later that same year. Similar to NephroGene, these tests are based on the company's gene expression analysis method.
Ampel released early-access versions of both LuGene and DermaGene last year.