Method for diagnosing and treating subjects having single nucleotide polymorphisms in chromosome 2, 2:107,510,000-107,540,000 locus

Inventors

Zisapel, Nava • Laudon, Moshe

Assignees

Neurim Pharmaceuticals 1991 Ltd

Abstract

Methods and products for identifying individuals who are likely to respond in a positive (benefit) or negative (harm) manner to a pharmacological drug treatment intended for treating or preventing a neuropsychiatric disorder, neurodegeneration, sleep-wake cycles such including and not limited to Alzheimer's disease, schizophrenia, autism and attention disorders based on single nucleotide polymorphisms (SNP) chromosome 2, 2:107,510,000-107,540,000 locus (as disclosed in the Genome Reference Consortium Human genome build 37 (GRCh37)).

Core Innovation

The invention relates to genotype-guided, paradoxical response-based treatment selection for a human subject diagnosed with symptomatic AD or early onset dementia. It directly detects carrier status by assessing whether the subject carries at least one C allele at rs12328439 (T>C), at least one A allele at rs62155556 (T>A), at least one T allele at rs62155557 (G>T), at least one A allele at rs62155558 (G>A), at least one G allele at rs17033479 (A>G), or at least one A allele at rs9789618 (T>A). The genotype information predicts different therapeutic benefit versus harm depending on the diagnosed condition.

The core selection rule distinguishes between subjects who are carriers and subjects who are not carriers of the specified SNP alleles. For a subject diagnosed with symptomatic AD or early onset dementia that is a carrier, the subject is administered a therapeutic agent that is not a melatonin/5-HT1A receptor agonist or is administered 3 to 10 mg piromelatine. For a subject diagnosed with symptomatic AD or early onset dementia that is not a carrier, the subject is administered the melatonin/5-HT1A receptor agonist.

The invention further incorporates DNA handling and allele-determination approaches using probe arrays. DNA is extracted and/or amplified from a sample from the human subject, and the DNA is contacted with an array comprising a plurality of probes suitable for determining the identity of one or more alleles selected from the specified SNP allele set. In this way, the method directly detects carrier status and then administers the therapeutic agent according to the carrier-based rule.

Claims Coverage

The document includes two independent methods. Across the two independent claims, six SNP allele positions are used to determine carrier status, and the administered therapy is chosen by an explicit carrier versus not-a-carrier rule while specifying a DNA-probe-array allele-detection workflow in one independent claim.

Overall, the claim coverage centers on determining whether a symptomatic AD or early onset dementia subject is a carrier of specified SNP alleles and then selecting therapy according to a carrier/not-a-carrier rule, with one independent claim emphasizing DNA contacted with a probe array to determine allele identity.

Stated Advantages

Documented Applications