Bernard Lerer, MD, and Lior Greenbaum, MSc, Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah University Hospital.
Background
Psychoses are serious mental illnesses characterized by defective or lost contact with reality. Psychotic patients may suffer hallucinations and delusions as part of their disease. Psychoses exact a tremendous emotional and economic toll on patients, their families, and society as a whole. Traditional (typical) antipsychotic drugs and atypical antipsychotic drugs are indispensable in the pharmacological treatment of schizophrenia and other neuropsychiatric conditions that are associated with psychotic states. In tandem with the benefits of antipsychotic drugs, significant risks are associated with their use. The risks most commonly associated with typical antipsychotic drugs are acute and chronic neurological adverse effects involving voluntary and involuntary musculature, the most common being extra-pyramidal symptoms (EPS). The intolerable side effects induced by antipsychotic drugs often lead patients to stop using them. Therefore, early detection of susceptibility to side effects and appropriate choice of treatment are of critical importance. Currently existing methods do not meet the requirement to determine susceptibility to EPS before initiation of antipsychotic treatment.
There is growing recognition worldwide of the critical importance of early diagnosis of predisposition to the side effects induced by antipsychotic drugs.
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. NIH official information indicates 2.4 million Americans suffering from schizophrenia. Schizophrenia is treated with antipsychotic drugs, as are other neuropsychiatric disorders that may be accompanied by psychosis. Therefore, antipsychotic drugs are widely used and represent an extremely large market. At present, prescription of typical antipsychotic drugs is severely limited by concerns regarding the development of EPS. The newer atypical drugs, which induce less EPS, cause other troublesome adverse effects and are not more effective than the typical drugs. This situation has created an urgent need for a diagnostic test that will allow clinicians to identify a priori patients who have a higher risk of developing EPS and those who are relatively resistant. The cost of typical antipsychotics, almost all of which are off-patent, is a fraction of that of the newer agents. There is constant pressure from health care providers to limit the prescription of the newer, more costly, atypical anti-psychotic drugs.
The Innovation
The discovery made by Prof. Lerer’s group at Hadassah provides methods for detecting genotypes associated with susceptibility to and also resistance to EPS induced by antipsychotic drugs. The findings of the invention indicate that the presence of specific SNP alleles and haplotypes in the RGS2 gene can be used to predict susceptibility and/or resistance to EPS and may thus be helpful in designing a treatment regimen that includes typical antipsychotics. The method of the invention is based in part on the discovery that specific SNPs and haplotypes in the RGS2 gene are associated with relative resistance to development of EPS during treatment with typical antipsychotics, while other SNPs and haplotypes in the RGS2 gene are associated with onset or worsening of EPS upon treatment with typical antipsychotic drugs.
The findings have been supported in a replication study conducted by Prof Lerer's group. Carriers of a specific allele of one of the associated SNPs were 3-5 times less likely to develop EPS (antipsychotic-induced parkinsonism) than non-carriers. This particular allele has been shown to be functional with effects that can influence dopaminergic transmission.
Contact
Yuval Kupitz
Business Development, Pharmaceuticals and Diagnostics
Tel: +972-2-6778364
Email: yuvalk@hadasit.co.il
