Compositions and methods for detecting and treating neurological conditions
| Title: | Compositions and methods for detecting and treating neurological conditions |
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| Patent Number: | 8,518,638 |
| Publication Date: | August 27, 2013 |
| Appl. No: | 12/027834 |
| Application Filed: | February 07, 2008 |
| Abstract: | The present invention relates to the NIPA-1 proteins and nucleic acids encoding the NIPA-1 proteins. The present invention further provides assays for the detection of NIPA-1 polymorphisms and mutations associated with disease states, as well as methods of screening for ligands and modulators of NIPA-1 proteins. |
| Inventors: | Fink, John K. (Ann Arbor, MI, US); Rainier, Shirley (Sylvania, OH, US); Nicholls, Robert D. (Philadelphia, PA, US); Chai, Jinghua (Ardmore, PA, US) |
| Assignees: | The Regents of the University of Michigan (Ann Arbor, MI, US) |
| Claim: | 1. A composition comprising an isolated nucleic acid molecule at least 90% identical to SEQ ID NO: 6. |
| Claim: | 2. The composition of claim 1 , wherein said isolated nucleic acid molecule is at least 95% identical to SEQ ID NO: 6. |
| Claim: | 3. The composition of claim 1 , wherein said isolated nucleic acid molecule is SEQ ID NO: 6. |
| Claim: | 4. A composition comprising an isolated and purified nucleic acid sequence encoding a protein comprising the amino acid sequence of SEQ ID NO: 4. |
| Claim: | 5. A composition comprising an isolated and purified nucleic acid sequence encoding a protein comprising the amino acid sequence of SEQ ID NO: 3. |
| Claim: | 6. A composition comprising the nucleic acid molecule of SEQ ID NO: 1. |
| Claim: | 7. A composition comprising the nucleic acid molecule of SEQ ID NO: 2. |
| Claim: | 8. A composition comprising the nucleic acid molecule of SEQ ID NO: 5. |
| Claim: | 9. A method of detecting the presence or absence of a polymorphism in a NIPA-1 nucleic acid in a test sample, comprising the steps of: a) obtaining a test sample comprising all or part of a NIPA-1 nucleic acid; b) determining the sequence of all or part of the NIPA-1 nucleic acid in the test sample by assaying the sample; c) comparing the sequence obtained in step (b) with a NIPA-1 nucleotide sequence of a control nucleic acid sample, wherein said control sample comprises all or part of SEQ ID NO:5; d) determining the difference between the NIPA-1 nucleic acid sequence in said test sample and the NIPA-1 nucleotide sequence in said control sample; and e) identifying the test sample as containing a NIPA-1 polymorphism if it comprises at least one sequence difference from the control sample NIPA-1 nucleotide sequence. |
| Claim: | 10. The method of claim 9 , wherein the nucleic acid test sample comprises nucleic acids selected from the group consisting of DNA and RNA. |
| Claim: | 11. The method of claim 9 , wherein said difference between NIPA-1 nucleotide sequence in said nucleic acid test sample and SEQ ID NO: 5 is a C to G change at position 159 of SEQ ID NO: 5. |
| Claim: | 12. The method of claim 11 wherein the test sample is obtained from a human and wherein the detection of a C to G change at position 159 of SEQ ID NO: 5 between the test sample and control sample nucleotide sequences is indicative of the human having, or being at risk for developing, hereditary spastic paraplegia. |
| Claim: | 13. The method of claim 9 , wherein the method to determine the nucleotide sequence comprises one or more of the following: sequence analysis, and hybridization assays. |
| Claim: | 14. The method of claim 9 wherein the method to determine the nucleotide sequence includes PCR, RT PCR, or direct sequencing of the polynucleotides. |
| Claim: | 15. A method for identifying an individual having, or at risk of developing, hereditary spastic paraplegia (HSP) comprising: a) obtaining a biological sample comprising nucleic acid from said individual; b) determining the presence or absence of a G at position 159 of SEQ ID NO:5 in a NIPA-1 nucleic acid sequence in the biological sample by assaying the sample; c) identifying the individual as having HSP or as being at risk of developing HSP if a G at position 159 of SEQ ID NO:5 in the NIPA-1 nucleic acid sequence in said sample is detected thereby correlating the individual with having HSP or being at risk of developing HSP. |
| Claim: | 16. The method of claim 15 , wherein said assaying comprises contacting the nucleic acid in the nucleic acid sample with a fragment of SEQ ID NO:2 under highly stringent conditions, wherein the fragment binds to SEQ ID NO:2 but not to SEQ ID NO:1. |
| Claim: | 17. A method of determining the presence of, or risk of developing, hereditary spastic paraplegia (HSP) in a human, the method comprising the steps of: a) obtaining a nucleic acid sample from said human wherein the sample contains a NIPA-1 nucleic acid; b) assaying the nucleic acid sample to determine the presence or absence of a mutation in the NIPA-1 nucleic acid that results in a T to R substitution at position 45 of SEQ ID NO:3 or at position 53 of SEQ ID NO:7 in a NIPA-1 protein; and c) identifying the presence of HSP or a risk of developing HSP in said human if a mutation that results in a T to R substitution at position 45 of SEQ ID NO:3 or at position 53 of SEQ ID NO:7 in the NIPA-1 protein is detected, thereby correlating the human with having HSP or a risk of developing HSP. |
| Claim: | 18. The method of claim 17 wherein the NIPA-1 nucleic acid in the nucleic acid sample comprises SEQ ID NO: 1 and the mutation is a C to G substitution at position 134 of SEQ ID NO: 1. |
| Claim: | 19. The method of claim 17 wherein the assaying comprises direct sequencing of the NIPA-1 nucleic acid in the sample. |
| Claim: | 20. The method of claim 17 wherein the NIPA-1 nucleic acid in the nucleic acid sample comprises SEQ ID NO: 5 and the mutation is a C to G substitution at position 159 of SEQ ID NO:5. |
| Current U.S. Class: | 435/61 |
| Patent References Cited: | 7332282 February 2008 Fink et al. 2003/0092019 May 2003 Meyer 1618814 May 2005 WO2004058805 July 2004 |
| Other References: | Genbank Accession AC016204, Oct. 26, 2002. cited by examiner Genbank Accession No. CQ834738, Jul. 29, 2004. cited by examiner Rainer et al. (Am. J. Hum. Genetics, vol. 73, pp. 967-971, 2003). cited by applicant Kaneko, et al. (Movement Disorders, vol. 21, No. 9, 2006). cited by applicant Chen, et al. (Human Mutations, vol. 25, pp. 135-141, 2005). cited by applicant Hirschhorn, et al. (Genetics in Medicine, vol. 4, No. 2, pp. 45-61, Mar. 2002). cited by applicant Fink et al., “The hereditary spastic paraplegias,” Arch Neurol. 60:1045-1045 (2003). cited by applicant Rainer, et al., “NIPA1 gene mutations cause autosomal dominant hereditary spastic paraplegia (SPG6)” Am J Hum Genet 73:967-971 (2003). cited by applicant Reed et al., “A novel NIPA1 mutation associated with a pure form of autosomal dominant hereditary spastic paraplegia,” Neurogenetics 6:79-84 (2005). cited by applicant Chen, et al., “Distinct novel mutations affecting the same base in NAIPA1 gene cause autosomal dominant hereditary spastic paraplegia in two Chinese Families,” Hum Mutation 25:135-141 (2005). cited by applicant Ioannidis (Nature Genetics, vol. 29, pp. 306-309, Nov. 2001). cited by applicant JP Patent Application No. 2006-524073 Notice of Reasons of Rejection (Translation) dated Jun. 28, 2010. cited by applicant Rainier, et al., “NIPA1 Gene Mutations Cause Autosomol Dominant Hereditary Spastic Paraplegia (SPG6)”, Am. J. Hum. Genet. 2003, vol. 73, pp. 967-971. cited by applicant Fink, John K., “The Hereditary Spastic Paraplegias,” Arch. Neurol., 2003, vol. 60, pp. 1045-1049. cited by applicant Chai, et al., “Identification of Four Highly Conserved Genes Between Breakpoint Hotspots BP1 and BP2 . . .”, Am. J. Hum. Genet, 2003, vol. 73, pp. 898-925. cited by applicant Strausberg, R., GenBank: Database Embl/GenBank/Ddbj (online), Accession No. NM—144599, uploaded Jun. 11, 2002, retrieve on Jun. 23, 2010. cited by applicant Brandriff, B.F., et al., “DNA sequence mapping by fluorescence in situ hybridization,” Environ Mol Mutagen, 1991; 18(4):pp. 259062 (Abstract). cited by applicant Delidow, B.C., et al., “Quantative measurement of mRNAs by polymerase chain reaction,” Gene Anal Tech, Nov.-Dec. 1989;6(6);pp. 120-4 (Abstract). cited by applicant Canadian Office Action dated Apr. 10, 2008 from related Canadian Patent Application No. 2,536,108. cited by applicant Japanese Office Action (and English translation) dated Jun. 28, 2010 from related Japanese Patent Application No. 2006-524073. cited by applicant |
| Primary Examiner: | Goldberg, Jeanine A |
| Attorney, Agent or Firm: | Casimir Jones SC |
| Accession Number: | edspgr.08518638 |
| Database: | USPTO Patent Grants |
| Language: | English |
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