PUTATIVE TARGET FOR AN IMMUNOTHERAPEUTIC APPROACH TO PREVENT, AND STOP THE NEUROLOGICAL AND OTHER SYMPTOMS OF LESCH-NYHAN SYNDROME IN HUMANS: RECONSTRUCTED CDNA AND PROTEIN ANTISENSE TO THE HUMAN HPRT GENE

摘要

Point mutations and/ or deletions in the human hypoxanthineguanine phosphoribosyl transferase (HPRT) gene is believed to be the cause of Lesch-Nyhan syndrome in humans; however, the disastrous neurological symptoms which are characteristic of this disease cannot be easily explained by these mutations/deletions or even by the complete loss of the gene. There is no known cure for the disease. We reconstructed a cDNA (chprt) which is 100% homologous to a region of the antisense strand of hprt mRNA. The cDNA encodes a 30 amino acid protein (phrpt) which appears to be an intracellular activator of proteins involved in human neurological diseases. Because of the antisense relation with hprt mRNA, phprt cannot be expressed in humans carrying a normal wild type hprt gene; however, mutations in critical regions of the hprt gene can stop antisense repression and permit expression of phprt and the appearance of the pathophysiological symptoms of Lesch-Nyhan disease. The antisense protein is a very good target for immunotherapeutic reagents to stop the devastating neurological processes caused in humans afflicted with Lesch-Nyhan.