NEW YORK (360Dx) – Metafora Biosystems recently received support from the French government to undertake a study of its MetaGlut1 test for diagnosing glucose transporter 1 (Glut1) deficiency syndrome.
Set to take place over the next 30 months and to involve 3,000 patients across 60 centers in France, the effort could lead to Metafora's flow cytometry-based assay becoming the standard of care for diagnosing the disease in France.
Glut1 deficiency syndrome, also known as De Vivo disease, is rare and occurs when patients have a deficiency of the glucose transporter 1 protein, which is required for glucose to cross the blood-brain barrier. This lack of sugar in the brain can lead to epileptic seizures, ataxia, and developmental delay. The deficiency is currently identified using a lumbar puncture followed by a sequencing test to identify a genetic mutation in the SLC2A1 gene, which encodes the glucose transporter protein.
Metafora has developed a blood-based test for the disease that can be administered to newborns. It claims the test will improve diagnosis of Glut1 and enable patients to get treatment earlier.
"This is a rare disease and the symptoms can be very unspecific," said Metafora CEO Vincent Petit. "At the same time, treatment exists in the form of a ketogenic diet and physicians have been looking for a blood test as a way to screen these patients," he noted. "If the patient can be diagnosed early using our test, it can prevent the development of the disease."
Petit co-founded Metafora in 2011 to commercialize technology developed at the French National Center for Scientific Research (CNRS) for detecting abnormalities in cellular energetics. The company is based in Évry, south of Paris, and employs roughly a dozen people. It has raised around $5 million from angel investors to date.
Metafora's approach targets cellular nutrient transporters using receptor binding domain probes, or RBDs. This internally developed class of reagents attaches to the transporters, enabling scientists to measure, using automated flow cytometry instruments and informatics tools, their quantity and characterize how they are functioning.
That ability to detect abnormal nutrient consumption underpins the MetaGlut1 test.
"What we propose is to detect abnormal energy transport in cells," said Petit. "We were able to take the technology and make it available for routine use as an in vitro diagnostic for labs," he said. "Everything has been designed to run on high-throughput flow cytometry platforms."
Metafora obtained a CE-IVD mark for MetaGlut1 in February 2017 and partnered with Laboratoire Cerba, a clinical testing laboratory based in Saint-Ouen-l'Aumône, north of Paris, to make the test available in France and Belgium. The assay was also highlighted in an Annals of Neurology paper last summer. In that study, investigators tested MetaGlut1 in 30 patients with the disease as well as 346 healthy controls. They detected reduced Glut1 expression in patients with the syndrome, including those who had inconclusive results using conventional methods.
While the CE-IVD mark and paper have helped to encourage interest in the test, to see a real uptake of the assay, Metafora needs to gain reimbursement for MetaGlut1, which is the rationale for the new study, Petit said.
The French Ministry of Solidarity and Health recently agreed to finance the trial of the test in part via Forfait Innovation, a government program that provides financial support for early-stage medical technologies. Petit said that Metafora will actually be financing part of the study with the help of its investors, but that Forfait Innovation has agreed to reimburse it for the test. The effort aims to show that Metafora's test can detect Glut1 deficiency more efficiently than lumbar puncture and sequencing. Metafora expects the results of the study will be published in 2021.
"We would like to confirm the diagnostic value of the test, that it is as easy to perform as lumbar puncture is in patients suspected with Glut1 deficiency," said Fanny Mochel,  head of the reference center for adult neurometabolic diseases at the Hôpital de la Pitié-Salpêtrière in Paris and the principal investigator of the study.
"We want to see how in real life we can better characterize patients using the test," said Mochel. "The question is if we are going to diagnose more patients than we have been identifying in recent years."
Currently there is no consensus as to the prevalence of Glut1 deficiency syndrome. A 2006 Australian study estimated its incidence to be 1 in 90,000. However, it is possible that many with the disease simply go undiagnosed. "Prevalence is always a bit of an issue when it comes to rare diseases," acknowledged Mochel.
According to Mochel, diagnosing patients via lumbar puncture is not a comprehensive method, as some that suffer from Glut1 deficiency still show normal lumbar puncture results. In addition, lumbar puncture requires hospitalization, making it more expensive than a blood-based test.
Therefore, should Metafora's test diagnose more patients than lumbar puncture in a less invasive and more accurate way, the investigators will consider the outcome a success, setting it up for potential adoption in routine care, Mochel said.
Should that happen, the test would be used in neuropediatric and neurology departments in France not only to screen patients suspected of having Glut1 deficiency, but any who present symptoms associated with the disease, such as cognitive impairment, movement disorders, epilepsy, or all three, Mochel said.
"The point of the study is to convince the authorities that this is worthy of reimbursement and should be considered a routine diagnostic test," said Mochel. She noted that it is unclear how many samples will ultimately be screened using MetaGlut1, considering it's a prospective study, though the researchers hope to look at between 2,000 and 3,000 samples in France.
For Metafora, a successful outcome will not only result in the adoption of MetaGlut1 for routine use in France, but will allow it to better reach customers in other countries.
"This is quite a big study that will demonstrate that the product will be used for working clinical practice," said Petit."But it will also allow the company to promote the test globally," he said, citing other European countries, the US, and China as Metafora's most immediate target markets after France. "This large clinical study is key to providing clinical evidence for introducing the test in other countries, and to make it a good test in terms of feasibility, as well as sales," he said.
In terms of serving markets outside of France, Petit said that Metafora is currently "talking to opinion leaders" in Asia and the US. "The next step is to identify a market entry strategy," he said, adding that Metafora will outline its plans for international expansion at a later date. However, it will maintain its strategy of manufacturing and marketing the tests while partnering with clinical labs, such as Laboratoire Cerba, to offer them.
"We are looking for new partners to make the test available for users across Europe, North America, and Asia as well," he said.
Metafora continues to make its RBD technology available to partners for research use as well, and has other tests in its pipeline, including for use in cancer diagnostics, Petit said, though he did not elaborate. It is clear, though, that the firm sees MetaGlut1 as a flagship assay that will allow it to establish a route to market for other assays as they become available. "We think we are at the beginning of a big story with this first test," said Petit.