University of Florida,
Departments of Medicine & Physiology
Health Science Center
PO Box 100204
Gainsville, Florida 32610-0204
Tel: (352) 392-8952, Fax: (352) 392-8481 Dear

Enclosed is a very brief summary of the background for our study of "exorphins" in the genesis and treatment of autism.

Should you be interested after you have read it, please take it to your doctor and discuss it with him. If he, too, is interested, have him call or write us and we will be happy to discuss it with him.

We are a research lab and while the primary interest behind any research project is to help patients, both present and future, the only way we can be sure of learning is to have a study set up that maximizes the likelihood of accumulating good information and this requires working with a physician who can see your child at frequent intervals so that all of us, patients, physicians and laboratory scientists, have confidence in the reliability of the data we obtain.

Sincerely yours,

J. Robert Cade, M.D.
Professor of Medicine and Physiology

Attachment:

Prior to 1960, most investigators did not consider childhood autism to be a distinct illness but considered it to be a childhood form of schizophrenia. Only during the past fifteen years has there been a concensus [sic] that schizophrenia and childhood autism are different entities.

In 1966, Dohan called attention to the correlation between incidence and severity of schizophrenia and a diet high in cereals such as wheat, barley, oats and rye. In 1977, Wagemaker and Cade reported that dialysis with an artificial kidney which removes small particles from the blood produced a significant improvement in the symptoms of schizophrenia. In 1981, Reichelt reported that both adult schizophrenics and autistic children had excessive amounts of small polypeptides in their urine and that at least some of the peptides were bioactive. Reichelt, in 1990, reported that a group of patients with childhood autism and hyperpolypeptiduria showed significant improvement in behavior when put on a diet free of gluten and casein.

Our studies, which are still in progress, have shown:

I.

• 95% of patients with schizophrenia or childhood autism have a significant hyperpolypeptiduria.
• All of these patients had a greatly increased amount of peptides which have a morphine-like activity and are derived from either casein (milk) or gliadin (wheat).

• The degree of the polypeptiduria can be decreased by either dialysis, diet or the two in combination.
• As the polypeptiduria decreases, the symptoms of schizophrenia or autism decreases.
• If the polypeptiduria can be reduced to normal range, most patients either improve dramatically or become completely normal. A very rigid adherence to a gluten/casein-free diet is required to accomplish this.
• When the urine peptides are fractionated, the most common peptide is b-casomorphine-7 which was found in large amounts in all of the autistic and schizophrenic patients. It was found in small amounts in about half of our normal subjects.
• Gliadorphin-7 was found in very large amounts in 48% of schizophrenics and 54% of autistic patients, while it was found in 32% of normals in very small amounts.

• Among autistic children, 30% had high titer IgA antibodies to both gluten and casein. Among schizophrenics, 86% had high titer IgA antibodies to gluten and 67% to casein. In normal individuals, less than 10% have IgA antibodies to gluten and casein and these are almost all low titer.
• Among autistic children, 87% had high titer IgG antibodies to gluten and 90% to casein, while among schizophrenic patients 86% had high titer IgG antibodies to gluten and 93% to casein.
• The presence of IgG antibodies means that gluten and casein with their morphine-like components get into blood (where they should not be) in large amounts. The presence of IgA antibodies means the intestinal mucosa is sensitive to gluten or casein. The markedly different incidence of IgA antibodies, comparing autism to schizophrenia, means there are two different intestinal abnormalities that allow gluten and casein to enter the blood.

Mean Score During the Control Period and while on a Gluten/Casein-free Diet for Nine Characteristics which Occur Frequently in Autistic Children

(Legend is 0-Normal, 1-Good, 2-Fair, 3-Poor, and 4-Very Poor)

                              - - - - - On Diet - - - - -
                    Control  1 mon   3 mon   6 mon  12 mon

Social Isolation:     3.5      2.9     1.9     1.4     1.4

Eye Contact:          3.2      2.4     2.7     1.2     1.2

Mutism:               2.8      2.1     1.5     0.9     0.8

Hygiene:              1.9      1.9     1.2     1.2     1.2

Learning Skills:      3.3      2.8     2.1     1.6     1.2

Hyper-Activity:       3.1      2.1     1.7     1.6     1.5

Sterotypal Activity:  3.3      2.8     2.1     1.5     1.1

Self-Mutilation:     0.63     0.57    0.37    0.47    0.30

Panic Attacks:        1.5      1.3    0.80    0.83    0.45