Frataxin expression constructs

A method of increasing frataxin levels in a subject having a frataxin deficiency, the method comprising administering to the subject:

• an adeno-associated viral (AAV) vector, wherein said AAV vector comprises a nucleic acid molecule encoding human frataxin operably linked to:
• a 5′UTR selected from 5U2, FTH1, GAPDH, and RPL6-5′Splice;
• a 3′UTR selected from a SV40 early adenylation sequence, a SV40 late adenylation sequence, a human growth hormone polyadenylation sequence (hGHpA), and a synthetic 3′ regulatory element having a nucleic acid sequence of SEQ ID NO:7;
• and
• a control element that directs transcription and/or translation,
• wherein the frataxin encoded by the nucleic acid molecule is produced by the subject at a level that is at least 25% of frataxin levels produced by a subject not having a frataxin deficiency,
• wherein the administering comprises intrathecal (IT) administration, intracerebroventricular (ICV) administration, intraparenchymal administration, intracerebellar administration, or a combination thereof.

A method of treating at least one symptom of Friedreich's Ataxia in a subject in need thereof, the method comprising administering to the subject a pharmaceutical formulation comprising:

• (a) an adeno-associated viral (AAV) vector, wherein said AAV vector comprises a nucleic acid molecule encoding human frataxin operably linked to a 5′UTR, a 3′UTR, wherein:
• the 5′UTR is FTH1 and the 3′UTR is a SV40 early polyadenylation sequence or a SV40 late polyadenylation sequence;
• the 5′UTR is GAPDH and the 3′UTR is a SV40 late polyadenylation sequence or a synthetic 3′ regulatory element having a nucleic acid sequence of SEQ ID NO:7;
• the 5′UTR is 5U2 and the 3′UTR is a human growth hormone polyadenylation sequence (hGHpA) or a synthetic 3′ regulatory element having a nucleic acid sequence of SEQ ID NO:7;
• or
• the 5′UTR is RPL6-5′Splice and the 3′UTR is a synthetic 3′ regulatory element having a nucleic acid sequence of SEQ ID NO:7, and
• (b) phosphate buffer solution (PBS) or Dulbecco's phosphate buffer solution (DPBS),
• wherein the frataxin encoded by the at least one nucleic acid molecule is produced by the subject at a level sufficient to treat at least one symptom of Friedreich's Ataxia in the subject;
• and
• wherein the at least one symptom of Friedreich's Ataxia comprises loss of coordination in the arms and/or legs;
• and
• wherein the administering comprises intrathecal (IT) administration, intracerebroventricular (ICV) administration, intraparenchymal administration, intracerebellar administration, or a combination thereof.