Pipeline

Enzerna is focused on addressing three major nucleotide repeat-causing disorders. These three ASRE constructs will allow us to potentially address dozens of disorders caused by these repeats

 
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About Huntington’s Disease

Huntington’s disease (HD) is a major polyglutamine autosomal dominant disorder that affects about 1/10,000 people. The polyglutamine repeat expansion within the Huntingtin protein (HTT) is associated with the depletion of neurons and an increased number of glial cells in the region of the brain critical for movement, memory, and decision-making. All HTT proteins have the polyglutamine repeats, but the number of repeats influences the onset, progression, and severity of the disease. Normal individuals have between 7-34 CAG repeats, while Individuals with ≥40 repeats develop HD. Since HD patients have one normal and one mutated HTT allele with long CAG repeats, an attractive therapeutic strategy would be to selectively degrade the product of mutated allele.  Therapeutic strategies directly targeting total HTT mRNA (healthy and disease allele), such as antisense oligonucleotides (ASO), have produced promising results. However, if selective reduction of mutant HTT expression is not accomplished, it is still unclear whether elimination of the normal Htt transcript would lead to adverse consequences.

About Myotonic Dystrophy

Myotonic muscular dystrophy (DMD) is a genetic disorder characterized by muscle degeneration and weakness. It is a common form of muscular dystrophy that generally begins in adulthood. Myotonic dystrophy can be categorized into myotonic dystrophy type 1 (DM1) and myotonic dystrophy type 2 (DM2). Myotonic dystrophy type 1 (DM1) is result of an abnormal DNA expansion in the DMPK gene on chromosome 19. Myotonic dystrophy type 2 (DM2) is caused by an abnormal expansion of DNA in the ZNF9 gene on chromosome 3. Myotonic dystrophy (DM) 1 is sub divided into congenital-onset DM1, juvenile-onset DM1, and adult-onset DM1. Common symptoms of myotonic dystrophy include stiffness and tightness of muscles, progressive muscle wasting, and muscle weakness in lower legs, neck, hands, and face. Cognitive disabilities can also occur. According to the Centers for Disease Control and Prevention, in 2016, prevalence of myotonic muscular dystrophy was 1 in every 8000 people.