Aspects of the disclosure relate to compositions and methods useful for treating neurological diseases and disorders. In some embodiments, the disclosure provides a method for treating a neurological disease or disorder comprising administration of both a viral vector comprising interfering nucleic acids (e.g., artificial miRNAs) and a viral vector comprising a CYP46A1 protein. In some embodiments, the disclosure provides a method for treating Huntington's disease comprising administration of both a viral vector comprising interfering nucleic acids (e.g., artificial miRNAs) targeting the huntingtin gene (HTT) and a viral vector comprising a CYP46A1 protein. In some embodiments, the viral vector comprises a modified viral capsid, such as for preferentially targeting cells in the CNS or PNS.

The present invention relates to a vector for use in the treatment of a polyglutamine repeat spinocerebellar ataxia, which vector comprises cholesterol 24-hydroxylase encoding nucleic acid.

The present invention relates to a vector for use in the treatment of a polyglutamine repeat spinocerebellar ataxia, which vector comprises cholesterol 24-hydroxylase encoding nucleic acid.

The present invention relates to a vector for use in the treatment of a polyglutamine repeat spinocerebellar ataxia, which vector comprises cholesterol 24-hydroxylase encoding nucleic acid.