CEREBRAL FOLATE IMBALANCES
Treatable auto-immune disorders
Folates are essential to the development of the human brain, particularly early in life when folate demand is highest. Cerebral folate imbalances occur when the body develops an auto-immune response to the folate transporter on the blood brain barrier. Researchers believe this response occurs when the immune system recognizes folate receptors in dairy products as foreign antigens, and turns the body's immune response against its own folate transport system, resulting in a deficiency of folates in the brain.
Research has shown that as many as 75% of autistic children suffer from this immune response and have low levels of folates in the brain and cerebral spinal fluid. Other mental disorders, including schizophrenia, epilepsy, and depression, are similarly associated with this immune response. The miracle is that this immune reaction can be overcome by high dose folates, if the correct folate is administered. People normally think of folic acid when folates are mentioned, but folic acid is not absorbed in high enough quantities to overcome this immune-response; excess folic acid is simply excreted in the urine. Levoleucovorin, a drug originally developed for use with cancer treatments is the answer. High doses of levoleucovorin have been shown to restore levels of folates in the cerebral spinal fluid, halt seizures, and restore normal brain functioning in autistic children and other people suffering from CFD.
Cerebral Folate Publications
Expect the unexpected in research. Check out the list of publications below, and don’t hesitate to contact me for more information.
RE Frye et al. (2016)
FOLINIC ACID IMPROVES VERBAL COMMUNICATION IN CHILDREN WITH AUTISM AND LANGUAGE IMPAIRMENT: A RANDOMIZED DOUBLE-BLIND PLACEBO-CONTROLLED TRIAL. MOL. PSYCHIATRY 00, 1–10 (2016).
This double blinded placebo controlled trial in 48 children, funded by the National Institutes of Health, demonstrated with statistical significance that a compounded form of folinic acid could improve language abilities and other social functions in autistic children. The study enrolled patients whether they had the immune response to the folate receptor or not, and analyzed the effect of the immune response post-hoc. Positive results were observed only in the subset of children positive for the immune response with a remarkable effect size of 0.9. Psychiatric products are normally approved with effect sizes 1/3 as large.
RE Frye et al. (2013)
CEREBRAL FOLATE RECEPTOR AUTOANTIBODIES IN AUTISM SPECTRUM DISORDER. MOL. PSYCHIATRY 18(3), 369–381 (2013).
This publication reports the discovery of an antibody to the folate receptor in 75% of 93 randomly selected autistic children. Cerebral spinal fluid was drawn in a subset of these patients and low folate levels observed in 100% of these children. High dose folates administered in an open label trial had significant impacts on social functioning and language skills.
VT Ramaekers et al. (2007)
FOLATE RECEPTOR AUTOIMMUNITY AND CEREBRAL FOLATE DEFICIENCY IN LOW-FUNCTIONING AUTISM WITH NEUROLOGICAL DEFICITS. NEUROPEDIATRICS 38(6), 276–281 (2007).
This publication reports early work by Belgian researcher Dr. Vincent Ramaekers diagnosing children with low functioning autism, epilepsy, and other neurologic sequelae based on the presence of folate receptor autoimmunity and consequent cerebral folate deficiency. The author reports exceptional results from high dose folate therapy, and that the best results are obtained when the child is treated early in life.
Treating autism and other CNS disorders
Cox Biosciences is a phase II/III pharmaceutical company developing proprietary treatments for autism and other disorders that require high dose reduced folate therapy.
Cox’s first drug product, LL-One, is a patent protected oral solution of levoleucovorin for the treatment of cerebral folate imbalances characterized by low folate concentrations in the brain and cerebral spinal fluid. Clinical studies conducted by pediatric neurologist Richard Frye at Phoenix Children's Hospital have yielded remarkable improvements in language skills in autistic children. Cox has developed a convenient liquid dropper and formulation that can be administered as early as the autism is suspected in a child. By treating this deficiency early, Cox hopes to halt the development of many autistic features and allow these children to live normal productive lives.
Cox is run by Clark Sullivan, ChE, JD, a lawyer with more than 28 years helping companies develop drug products. Cox has assembled an excellent team including high ranking FDA officials, one of the premiere folate scientists in the world, and regulatory consultants covering clinical outcome assessments and complex chemistry issues. In addition, Cox is closely advised by, or partners with:
Dr. Edward Quadros at Downstate Medical Center, the scientist who discovered the folate receptor immune response at the heart of Cox’s development programs.
Dr. Richard Frye at Phoenix Children’s Hospital, the pediatric neurologist who conducted the first studies of high dose folates in autistic children.
Iliad Neurosciences, a diagnostic company in Plymouth Meeting, Pennsylvania that developed and markets the test for the folate receptor immune response.
Cerbios-Pharma, a reduced folate manufacturer in Lugano Switzerland, which has provided invaluable support during formulation development and stability testing.
Aprofol AG, a Swiss drug development company that has supported the development of Cox’s finished drug product using Swiss and German technology.