Gene responsible for stargardt-like dominant macular dystrophy

• US 20040067226A1
• Filed: 10/03/2003
• Published: 04/08/2004
• Est. Priority Date: 05/16/2000
• Status: Active Grant

• Current Assignee: Johns Hopkins University, Merck & Co., Inc.
• Original Assignee: Johns Hopkins University
• Inventors: Li, Wen, Zhang, Kang, Petrukhin, Konstantin
• Granted Patent: US 7,091,005 B2
• Time in Patent Office: Days
• US Class Current: 424/94.5
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: C07K 14/705 Receptors; Cell surface antigens; Cell surface determinants tumour specific antigens C07K14/4748
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers
• CPC Class Codes: C12Q 2600/158 Expression markers

Abstract

The gene responsible for Stargardt-like macular dystrophy has been identified, along with its normal allelic form. The mutant gene encodes a mutant protein containing a frameshift mutation, resulting in abnormal fatty acid synthesis and transport in the retina. Also disclosed are assays for Stargardt-like macular dystrophy and therapies.

Claims

1. An Elongation of Fatty Acids (ELF) protein, free from associated proteins, comprising the amino acids shown in SEQ.ID.NO. 1.

2. A pharmaceutical composition comprising the protein of claim 1 and a pharmaceutically acceptable carrier.

3. A pharmaceutical composition according to claim 2 wherein the composition is an ophthalmic composition.

4. A method of treating, preventing or lessening the severity of Stargardt-like macular dystrophy comprising administering a pharmacologically effective amount of the composition of claim 2 to an individual at risk or who manifest symptoms.

5. An Elongation of Fatty Acids (ELF) protein, free from associated proteins, comprising the amino acids shown in SEQ.ID.NO. 2.

6. Mouse ELF protein, free from associated protein, comprising the amino acids shown in SEQ.ID.NO. 5.

7. A method of determining if an individual is at risk for developing symptoms of Stargardt-like macular dystrophy comprising determining if the individual carries a gene encoding the protein of SEQ.ID.NO. 1 or SEQ.ID.NO. 2 wherein the protein of SEQ.ID.NO. 2 is associated with Stargardt-like macular dystrophy, and the protein of SEQ.ID.NO. 1 is not.

8. A method according to claim 7 wherein the determination is an assay comprising

contacting a probe and a nucleic acid sample of the individual, wherein hybridization of the probe and the nucleic acids in the sample indicates that a normal ELF nucleic acid is present in the sample.

9. A method according to claim 7 wherein the determination is an assay comprising

contacting a probe and a nucleic acid sample of the individual, wherein hybridization of the probe and the nucleic acids in the sample indicates that a mutant ELF nucleic acid is present in the sample.

10. A method according to claim 7 wherein the determination is an assay comprising

obtaining a sample of the protein produced by the individual and

determining if the sample is the protein of SEQ.ID.NO. 1 or SEQ.ID.NO. 2.

11. A method according to claim 10 wherein the determining step comprises contacting the protein sample with an antibody specific for either the protein of SEQ.ID.NO. 1 or SEQ.ID.NO. 2, and determining if binding occurs.

12. A method of isolating nucleic acids encoding an ELF protein in a non-human mammal comprising contacting a retinal library from the non-human mammal with a probe from human ELF DNA.

13. A nucleic acid encoding an amino acid selected from the group consisting of:

SEQ.ID.NO. 1, SEQ.ID.NO. 2, and SEQ.ID.NO. 5, free from associated nucleic acids.

14. A nucleic acid of claim 13 which is DNA.

15. cDNA selected from the group consisting of SEQ.ID.NO. 3, SEQ.ID.NO. 4, and SEQ.ID.NO. 6.

16. A DNA, free from associated nucleic acids comprising the sequence of SEQ.ID.NO. 7.

17. A vector comprising an ELF expression cassette.

18. A host cell comprising a vector of claim 17.

19. A method of making an ELF protein comprising culturing a host cell comprising an ELF expression cassette, and recovering ELF protein.