The invention relates to inhibitors of CDK12 (cyclin-dependent kinase 12), and there use in the treatment or prevention of a disorder in a subject caused by the generation of repeat expansion transcripts.

The invention relates to inhibitors of CDK12 (cyclin-dependent kinase 12), and there use in the treatment or prevention of a disorder in a subject caused by the generation of repeat expansion transcripts.

The present disclosure provides methods for predicting a patient's response to biglycan therapy for diseases or conditions associated with an abnormal level or activity of biglycan; disorders associated with an unstable cytoplasmic membrane, for example, due to an unstable dystrophin associated protein complex (DAPC); disorders associated with abnormal synapses or neuromuscular junctions, including those resulting from an abnormal MuSK activation or acetylcholine receptor (AChR) aggregation. Examples of such diseases include muscular dystrophies, such as Duchenne's Muscular Dystrophy, Becker's Muscular Dystrophy, neuromuscular disorders and neurological disorders. This application also provides combination therapeutics, such as a biglycan therapeutic and a utrophin therapeutic.

Embodiments of this invention include synthetic compounds (NRP analogues) of peptides termed neural regeneration peptides (NRPs). NRP analogues are made by substituting amino acids in the native peptide sequence, modifying amino acids chemically, by replacing amino acids with synthetic moieties, by stabilizing -turns, acetylation of terminal glycine residues or by cyclization. NRP analogues can be used to treat a variety of conditions involving degeneration of neural cells, and includes treating disorders of the nervous system, including peripheral neuropathy, multiple sclerosis, diabetic peripheral neuropathy, neurotoxin-induced neurodegeneration, and amyotrophic lateral sclerosis.

Embodiments of this invention include synthetic compounds (NRP analogs) of peptides termed neural regeneration peptides (NRPs). NRP analogs are made by substituting amino acids in the native peptide sequence, modifying amino acids chemically, by replacing amino acids with synthetic moieties, by stabilizing -turns, acetylation of terminal glycine residues or by cyclization. NRP analogs can be used to treat a variety of conditions involving degeneration of neural cells, and includes treating disorders of the nervous system, including peripheral neuropathy, multiple sclerosis, diabetic peripheral neuropathy, neurotoxin-induced neurodegeneration, and amyotrophic lateral sclerosis.