Bernard Lerer, MD and Kyra Kanyas, MA., Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah University Hospital and Daniela Zalcenstein-Amann, MSc. Eng., Department of Molecular Genetics, Weizmann Institute of Science.
Background
Schizophrenia is a severe neuropsychiatric disorder that affects thought, perception and cognition and has its onset in late adolescence and early adulthood. It is a common disorder with a lifetime risk of ~1% worldwide. As a chronic illness that is the leading cause of long-term psychiatric hospitalization, schizophrenia poses a major public health problem. Therefore, early detection of schizophrenia, particularly in the prodromal phase before florid symptoms have erupted, and timely implementation of treatment, are of critical importance.
Current methods for identifying susceptibility to schizophrenia are limited to clinical, psychiatric evaluation and are in need of improvement. There are no laboratory tests available.
There is growing recognition worldwide of the critical importance of early diagnosis and treatment of schizophrenia.
Market
Review of published data indicates that the median point prevalence of schizophrenia is 4.6 per 1000 worldwide. Surveys carried out in various countries, show incidence rates of 0.1-0.4 per 1000 population per year. This means 1000 to 4000 new cases per year in a country of 10 million people and 25 times that number in the United States. The number of individuals considered being at high risk due to a family history and sub-syndromal clinical manifestations can be conservatively expected to be at least 5 times as great. Thus, the market for a diagnostic kit to aid in the prediction of susceptibility to schizophrenia is potentially very large.
The Innovation
A genome scan carried out by Prof. Lerer’s group at Hadassah on a sample of families affected with schizophrenia, led to the discovery of a strong linkage signal on chromosome 6q23. This signal was further explored by typing single nucleotide polymorphisms (SNPs) in the vicinity of the linkage peak. A strong genetic association with schizophrenia for single SNPs and haplotypes in a 500 kb genomic region of high linkage disequilibrium was identified within the 95% confidence interval of the linkage peak. Within this region the association signal was strongest in the Abelson Helper Integration Site 1 (AHI1) gene and an adjacent, non-annotated primate-specific mRNA, called C6orf217. The significance of the association was unusually strong and the results focusing on AHI1 were supported by a second, independently recruited family sample. AHI1 has a potentially important role in brain development and mutations in the gene have been shown to be a molecular cause of the severe neurological disorder, Joubert Syndrome. Comparative genomic analysis has suggested accelerated evolution of AHI1 in the human lineage.
deCODE genetics and researchers from Landspitali University Hospital, Reykjavik, Iceland, have recently published findings (European Journal of Human Genetics (2007), 1-4) which support the involvement of the AHI1 locus in schizophrenia.
Contact
Yuval Kupitz
Business Development, Pharmaceuticals and Diagnostics
Tel: +972-2-6778364
Email: yuvalk@hadasit.co.il
