Gene therapies for lysosomal disorders
Inventors
Abeliovich, Asa • Heckman, Laura • RHINN, Herve
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12570963-B2
Publication Date
2026-03-10
Expiration Date
Abstract
The disclosure relates, in some aspects, to compositions and methods for treatment of diseases associated with aberrant lysosomal function, for example Parkinson's disease (PD) and Gaucher disease. In some embodiments, the disclosure provides expression constructs comprising a transgene encoding beta-Glucocerebrosidase (GBA) or a portion thereof alone or in combination with one or more PD-associated genes. In some embodiments, the disclosure provides methods of Parkinson's disease by administering such expression constructs to a subject in need thereof.
Core Innovation
The document discloses gene therapy approaches for lysosomal disorders, including Parkinson’s disease associated with GBA1 and Gaucher disease. It uses AAV-based expression constructs to encode lysosomal genes and/or Parkinson’s disease-associated genes in the central nervous system. The constructs are provided singly or in combinations intended to address lysosomal dysfunction relevant to these disorders.
The document further discloses AAV expression constructs that optionally include inhibitory nucleic acids targeting α-Syn (SNCA/SCNA) and/or TMEM106B. It also discloses vector design features in the expression constructs, including codon optimization, promoter/enhancer elements, IRES, and self-cleaving 2A peptides (T2A or P2A). Additional disclosed components include AAV ITR flanking and polyA elements, including WPRE and bGH polyA.
The document also describes modifications involving the AAV ITR region placement, including positioning in relation to a modified ITR “D” region, to improve packaging and/or reduce toxicity. It states that the gene therapy constructs may act synergistically to reduce Parkinson’s disease signs. The disclosure includes nonclinical and in vitro assessment concepts using mouse models, including a CBE chemical mouse model and a 4L/PS-NA genetic model, and measurements such as GCase activity, glycolipid substrate levels, biodistribution, and cell-based expression or knockdown readouts.
Claims Coverage
Not explicitly described in patent.
Not explicitly described in patent.
Stated Advantages
Documented Applications
Use for gene therapy approaches for lysosomal disorders, including Parkinson’s disease associated with GBA1 and Gaucher disease.
Assessment of nonclinical outcomes in a CBE chemical mouse model and a 4L/PS-NA genetic mouse model with motor and cognitive outcomes.
Measurement-focused applications including evaluation of CNS/CSF substrate levels, GCase activity, and vector biodistribution.
Clinical trial concept application for PD/LBD/Gaucher, including direct CNS delivery approaches such as intracisterna magna/sub-occipital injection and other intracranial routes mentioned, including intracerebroventricular, intrathecal, and intraventricular delivery.
Interested in licensing this patent?