The PATrOL™ platform gives NeuBase the ability to tackle a multitude of diseases efficiently and cohesively. Our initial focus is on neurological and neuromuscular diseases.
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Central Nervous System, Neuromuscular and Other Programs
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CAG Repeats Causing Polyglutamine Aggregates
Huntington’s disease (HD) is a rare, dominantly-inherited, fatal neurodegenerative disorder, with symptoms such as uncontrolled movements, cognitive impairments and emotional disturbances worsening over time.
HD is primarily caused by the toxic aggregation of mutant huntingtin protein, leading to progressive neuronal loss in the brain. It is one of at least 30 known repeat expansion disorders or diseases caused by the repetition of simple DNA sequences. In the case of HD, the wildtype huntingtin gene has a region in which a three-base sequence, CAG, is repeated many times. When CAG is repeated 35 or fewer times in this region, the resulting protein behaves normally. When CAG is repeated more than 36 times in this region, the resulting protein becomes toxic and causes HD.
Current therapies for patients with HD can only manage individual symptoms. There is no approved therapy that has been shown to delay or halt disease progression.
The PATrOL-enabled NT0100 program is currently in preclinical development for the treatment of HD. NeuBase is conducting preclinical studies with the goal of filing an IND for NT0100 by year end 2021.
CTG Repeats in DMPK Causing Splice Dysfunction and Haploinsufficiency
Myotonic dystrophy type 1 (DM1) is a rare, autosomal dominant disorder characterized by progressive muscle wasting and weakness. While commonly described as a muscle disease, it can also affect the eyes, heart and brain.
DM1 is a repeat expansion disorder caused by an abnormally expanded section of the DMPK gene, which plays a role in cellular communications within heart, brain and muscle cells. The mutated DMPK gene produces an expanded version of DMPK mRNA, which then forms clumps inside cell nuclei due to its abnormal length. These clumps then interfere with the function of many other proteins, leading to the many symptoms associated with this disease.
There is currently no cure for DM1, and treatment is usually targeted at managing symptoms as much as possible.
The PATrOL-enabled NT0200 program is currently in preclinical development for the treatment of DM1. The PATrOL platform is uniquely positioned to treat DM1 due to the technology’s ability to target and open up aberrant secondary RNA structures in the mutant transcript, thereby displacing sequestered splice proteins as well as normalize DMPK protein levels in cells thereby restoring normal cellular function. Data exists that show that the DMPK protein is important for normal adult function, and we believe that strategies which degrade this protein as a mechanism to resolve nuclear aggregates may have downstream negative consequences.
Due to the advantages of the PATrOL™ platform, NeuBase is positioned to address a variety of genetic diseases.