AONM is pleased to offer the FRAT® (Folate Receptor Autoantibody Test), developed by Religen Laboratories in the USA. This specialised diagnostic blood test identifies autoantibodies directed against Folate Receptor Alpha (FRα)—a key protein responsible for transporting folate (vitamin B9) into cells and across the blood–brain barrier into the brain (Ramaekers et al., 2005).

The discovery of folate receptor autoantibodies was first reported in the New England Journal of Medicine, and since then a growing body of research has explored their clinical relevance in neurological and developmental conditions (Ramaekers et al., 2005; Rossignol & Frye, 2021).

The FRAT® Test was validated at Religen Laboratories’ CLIA-certified facility (CLIA certification number 39D2130307) and has been available internationally since 2016.

The FRAT® Test measures two types of antibodies that interfere with folate transport through the folate receptor.

Blocking antibodies
Blocking antibodies prevent folate from binding to the folate receptor, meaning folate cannot be transported into the brain.

Binding antibodies
Binding antibodies attach to other sites on the receptor and disrupt its normal function, which can also impair folate transport.

These antibodies may reduce the movement of folate across the blood–brain barrier, potentially leading to low folate levels within the brain even when blood folate levels appear normal (Ramaekers et al., 2005)

Folate (vitamin B9) is essential for a wide range of physiological processes, including:

• DNA synthesis and repair
• Red blood cell formation
• Neurotransmitter production
• Brain development and function
• Immune system regulation
• Homocysteine metabolism

Disruption in folate transport to the brain can affect neurological function because the brain has high metabolic and nutritional demands.

Autoantibodies against folate receptor alpha can interfere with the transport of folate into the central nervous system, contributing to Cerebral Folate Deficiency (CFD)—a condition characterised by low folate levels in the cerebrospinal fluid despite normal systemic folate levels (Ramaekers et al., 2005; Rossignol & Frye, 2021).

The folate receptor alpha is highly expressed in the choroid plexus, which serves as the main pathway through which folate enters the cerebrospinal fluid and brain. When autoantibodies interfere with this pathway, regions of the brain with high metabolic demand may be particularly vulnerable.

Research has identified folate receptor autoantibodies in a number of neurological and neurodevelopmental conditions, including:

• Cerebral Folate Deficiency
• Autism spectrum disorders
• Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS)
• Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS)

Emerging research suggests that impaired folate transport may affect metabolically active brain regions such as the basal ganglia, which play an important role in behaviour, cognition, and motor control (Wells et al., 2024).

Clinical studies have also investigated the potential benefits of folinic acid treatment in individuals with autism spectrum disorders and language impairment, particularly where folate metabolism abnormalities are present (Frye et al., 2018; Renard et al., 2020; Batebi et al., 2021; Wong et al., 2025; Zhang et al., 2025).

Clinicians may use the test to determine whether folate transport disruption could be contributing to symptoms and to guide potential treatment strategies.

Disclaimer
Test results are not intended to diagnose any disease. These tests were developed by VascularStrategies, LLC for Iliad Neurosciences.

The test requires a small blood sample.

• 2–4 ml of serum from a centrifuged blood sample
• Collected using a standard blood draw
• Sent to Religen Laboratories in the United States for analysis
  

FRAT® testing is performed exclusively by Religen, Inc. Due to increased demand and a record-high volume of specimens, please allow up to 75 days from the date the laboratory receives the sample for results to be reported.

Step 1 – Request a Test Kit
Contact AONM to request a FRAT® Test kit. ORDER ONLINE

Step 2 – Blood Collection
Your healthcare provider or local phlebotomy service collects the blood sample. The sample requires a centrifuge.

Step 3 – Shipment to the USA
AONM organises the paperwork for an international shipment to Religen Laboratories. Simply book the courier for a Monday, or Tuesday morning.

Step 4 – Receive Your Results
Results are returned to the ordering practitioner once analysis is complete.

If you would like to order the FRAT® Test or learn more about whether it may be appropriate for your patients, please contact AONM for further information.

The FRAT® Test is a blood test that detects antibodies against folate receptor alpha, which may interfere with folate transport into the brain (Ramaekers et al., 2005).

Yes. Folate transport across the blood–brain barrier can be impaired by folate receptor autoantibodies, resulting in reduced folate levels within the brain despite normal blood folate levels.

Yes. The test can be used for individuals of different ages where folate transport impairment is suspected.

The FRAT® Test is typically ordered through a healthcare practitioner who can interpret the results.

Batebi, N., Moghaddam, H. S., Hasanzadeh, A., Fakour, Y., Mohammadi, M. R., & Akhondzadeh, S. (2021). Folinic acid as adjunctive therapy in treatment of inappropriate speech in children with autism: A double-blind and placebo-controlled randomized trial. (5), 928–938. 

Frye, R. E., Slattery, J., Delhey, L., Furgerson, B., Strickland, T., Tippett, M., Sailey, A., Wynne, R., Rose, S., Melnyk, S., James, S. J., Sequeira, J. M., & Quadros, E. V. (2018). Folinic acid improves verbal communication in children with autism and language impairment: A randomized double-blind placebo-controlled trial. Molecular Psychiatry, 23(2), 247–256. https://doi.org/10.1038/mp.2016.168 

Ramaekers, V. T., Rothenberg, S. P., Sequeira, J. M., Opladen, T., Blau, N., Quadros, E. V., & Selhub, J. (2005). Autoantibodies to folate receptors in the cerebral folate deficiency syndrome. The New England journal of medicine, 352(19), 1985–1991. https://doi.org/10.1056/NEJMoa043160

Renard, E., Leheup, B., Guéant-Rodriguez, R. M., Oussalah, A., Quadros, E. V., & Guéant, J. L. (2020). Folinic acid improves the score of autism in the EFFET placebo-controlled randomized trial. Biochimie, 173, 57–61 https://doi.org/10.1016/j.biochi.2020.03.003 

Rossignol, D. A., & Frye, R. E. (2021). Cerebral folate deficiency, folate receptor alpha autoantibodies and leucovorin (folinic acid) treatment in autism spectrum disorders: A systematic review and meta-analysis. Journal of Personalized Medicine, 11(11), 1141 https://doi.org/10.3390/jpm11111141 

Wells, L., O’Hara, N., Frye, R. E., Hullavard, N., & Smith, E. (2024). Folate Receptor Alpha Autoantibodies in the Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) Population. Journal of personalized medicine, 14(2), 166. https://doi.org/10.3390/jpm14020166

Wong, C. M., Tan, C. S., Koh, H. C., Gan, X., Hie, S. L., Saffari, S. E., Yeo, J. G., & Lam, J. C. M. (2025). Folinic acid as a treatment for autism in children: A within-subjects open-label study on safety and efficacy. International Journal of Developmental Neuroscience, 85(1), e10402. https://doi.org/10.1002/jdn.10402 

Zhang, C., Chen, Y., Hou, F., Li, Y., Wang, W., Guo, L., Zhang, C., Li, L., & Lu, C. (2025). Safety and efficacy of high-dose folinic acid in children with autism: The impact of folate metabolism gene polymorphisms. Nutrients, 17(9), 1602 https://doi.org/10.3390/nu17091602