# US 12,006,549 B2 · Methods utilizing leukocyte RNA expression in prognosis evaluation of medical interventions for epilepsy

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- Number: US 12,006,549 B2
- Document ID: US12006549B2
- Status: Granted
- Kind: B2
- Application number: 17/269,092
- Filed: 2019-10-04
- Published: 2021-08-12
- Granted: 2024-06-11
- Earliest claimed: 2018-10-05
- Assignees: Arizona Board of Regents on Behalf of the University of Arizona
- Applicants: Arizona Board of Regents on behalf of the University of Arizona
- Inventors: Martin E. Weinand; Ryan Sprissler; Michael F. Hammer
- Web page: https://patentgrep.com/patent/US12006549B2

## CPC

- C12Q 1/6883: for diseases caused by alterations of genetic material
- C12Q 1/686: Polymerase chain reaction [PCR]
- A61N 7/00: Ultrasound therapy (lithotripsy A61B17/22, A61B17/225; massage using supersonic vibration A61H23/00 {; using ultrasound for introducing media into the body A61M37/0092})
- C12Q 2600/158: Expression markers
- G01N 2800/2857: Seizure disorders; Epilepsy
- G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- A61N: ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY (measurement of bioelectric currents A61B; surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body A61B18/00; anaesthetic apparatus in general A61M; incandescent lamps H01K; infrared radiators for heating H05B)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

Methods involving analysis of pretreatment leukocyte expression profiles for prognostic assessment of seizure outcome following a treatment or medical procedure, such as stereotactic laser amygdalohippocampotomy (SLAH). In one aspect, RNA sequencing (RNA-Seq) on whole blood leukocyte samples is taken from a patient with intractable epilepsy prior to SLAH. Differential expression (DE) analysis revealed 24 significantly dysregulated genes (≥2.0-fold change, p-value <0.05, and False Discovery Rate, FDR <0.05) useful in prognostic assessment.

## Claims

### Claim 1

A method of treating a subject with intractable epilepsy, comprising the steps of:
a) obtaining RNA from leukocytes from the subject;
b) based on the RNA present in the leukocytes, determining an expression level of 24 genes consisting of: FAM155A, ABCA4, ZFP57, IFI27, C5orf17, PLP1, PVRL2, FAM118A, GFAP, CDYL, CPEB4, FADS2, RSAD2, BIN3, BRSK1, AKAP7, IL22RA1, BGN, MMP8, PF4VI, MDGA1, ALOX15B, HBG1, and B4GALNT3;
c) comparing the determined expression level with a control expression level for each gene;
d) detecting upregulation of FAM155A, ABCA4, ZFP57, IFI27, C5orf17, PLP1, PVRL2, FAM118A, GFAP, CDYL, CPEB4, FADS2, RSAD2, BIN3, BRSK1, and AKAP7, and detecting downregulation of IL22RA1, BGN, MMP8, PF4VI, MDGA1, ALOX15B, HBG1, and B4GALNT3 relative to the control expression level for each gene; and
e) treating the subject with ablation treatment.

### Claim 2 (depends on 1)

The method of claim 1, wherein step c) comprises one or more of quantitative real time polymerase chain reaction (PCR) and digital droplet PCR.

### Claim 3 (depends on 1)

The method of claim 1, wherein said ablation treatment comprises stereotactic laser amygdalohippocampotomy (SLAH) ablation of the amygdala and the hippocampus, from the amygdala anteriorly to the hippocampus at least at a level of the tectum posteriorly.

### Claim 4 (depends on 1)

The method of claim 1, wherein said ablation treatment comprises an MRI-guided focused ultrasound or a focused ultrasound-based intervention.