Autism spectrum disorders (ASD) are developmental disorders affecting 1:88 children, and which appear to be associated with a variety of complex immune dysregulations including autoimmunity. The enzyme, alpha-N-acetylgalactosaminidase (Nagalase) deglycosylates Vitamin D Binding Protein (VDBP) rendering it incapable of activating macrophage defenses. 

Increased Nagalase activity has been associated with a variety of malignancies, immune disorders and viral infections. Macrophage activating factor (MAF) has been repeatedly published as an intervention to lower serum Nagalase activity for a variety of cancer and HIV patients. 

MAF is a naturally occurring protein with well-established safety and therapeutic benefit(s) supported by numerous human studies.

Uncontrolled observations of MAF therapy in Autism indicated substantial improvements in language, socialization and cognition. During this time a reduction in Nagalase levels was recorded.  Although Nagalase is a nonspecific marker of immune dysregulation, its observed levels in autism may have both etiological and therapeutic significance.

Autism, once a rare disorder, it is now approaching epidemic, if not pandemic, proportions.

While no consensus exists, this trend in autism is at least suggestive of an infective pathogen. Within this context, various organisms have been postulated to be involved, including: gastrointestinal infections,2 Polyomaviruses,3 Chlamydophila,4 Bornaviruses,5 Paramyxoviruses,6 and Borrelia burgdorferi.7 While any of these may contribute to a small percentage of autism cases, it seems unlikely that any of them indi¬vidually represents the origin of this epidemic.

Despite this uncertainty, growing evidence supports significant immune dysfunction, including autoimmunity, in autism.

One possible explanation for the pattern of immune dysregulation and observed in autism spectrum disorders (ASD) could be persistence of active pathogens, perhaps from the perinatal or a subsequent period of child development.11

Nagalase has been published as a biomarker associated with various types of cancer,22–24,29,30 systemic lupus erythematosus (SLE),13 influenza,14 and human immunodeficiency virus infection (HIV).31 It  appears to be an important indica¬tor of secondary immune dysregulation.

Nagalase is an enzyme that deglycosylates the Vitamin D binding protein (VDBP), rendering it inca¬pable of immune activation and thereby preventing its regulation of macrophage activation.18    It is noteworthy that vitamin D deficiency, either in pregnancy or during postnatal development, is an apparent risk factor for autism.19 The impact of Nagalase on VDBP transportation of vitamin D is not known. However, vitamin D deficiency is a known risk factor for autoimmunity.20

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