The data were published online on July 1 and will appear in the July 2019 issue of "Nature Medicine." The company said the publication describes research by Sangamo and collaborators at the CHDI Foundation, in which ZFP-TFs were engineered to selectively target the mutant form of the huntingtin gene and repress its transcription, selectively lowering production of the mutant Huntingtin protein
. Preclinical data from HD patient-derived fibroblasts and neurons demonstrated that a single administration of ZFP-TFs resulted in the selective repression of over 99% of HD-causing HTT disease alleles over a wide dose range, while preserving the expression of at least 86% of healthy wild-type HTT alleles, according to Sangamo.
Huntington's disease is an autosomal dominant neurodegenerative disorder caused by expansion of cytosine-adenine-guanine (CAG) trinucleotide repeats within the Huntingtin (HTT) gene on chromosome 4, which codes for the huntingtin protein
. (2,3) While the function of "normal" huntingtin protein
is not fully understood, it is known that CAG repeat expansion in the HTT gene of >35 repeats codes for a mutant huntingtin protein
RG6042 demonstrated its ability to reduce the toxic mutant huntingtin protein
(mHTT), which is believed to be the underlying cause of HD, in a Phase I/Ha study.
The overexpression of IncRNA AC111653.1 upregulated rno-Hypm gene substantially, indicating that this novel IncRNA is accurately associated with the huntingtin protein
But the Huntingtin protein
is expressed in every cell from the earliest stages of embryonic development.
In a Phase I/IIa study, RG6042 demonstrated its ability to reduce the toxic mutant huntingtin protein
(mHTT), which is believed to be the underlying cause of HD.
Mutations in the huntingtin gene cause the disease, resulting in the toxic aggregation of the huntingtin protein
The disease is caused by a defect in a section of DNA called the huntingtin gene, which normally carries the instructions for making the huntingtin protein
vital for brain development.
(2004) Distinct aggregation and cell death patterns among different types of primary neurons induced by mutant huntingtin protein
It encodes huntingtin protein
and is ubiquitously expressed in most tissues (Becanovic et al., 2015).
With functional MRI, Lee and colleagues scanned the brains of 26 children ages 6 to 18 who had inherited genetic instructions for a dangerous version of the huntingtin protein
. These kids will go on to develop Huntington's.