Symptomatic/QoL treatments:
those aimed at easing HD symptoms and improving quality of life. Examples are approved chorea treatments developed by Teva (deutetrabenazine) and Neurocrine Biosciences (valbenazine). SOM Biotech is also developing SOM3355 for the treatment of HD chorea.
Disease-modifying treatments:
those aimed at slowing or stopping the course of HD.
Somatic expansion:
when CAG repeats lengthen in individual cells over time. In HD, this happens at the highest rate in the vulnerable brain cells of the striatum. Companies like Harness, LoQus23, and Rgenta are developing therapies to combat expansion.
Cell replacement:
implanting new brain cells or using genetic methods to cause new neurons to be generated. NeuExcell Therapeutics and Sana Biotechnology are working on this therapeutic avenue.
S1R activation:
Prilenia’s drug, pridopidine, is known to increase signaling through a receptor called Sigma1 Alpha, in hopes of improving cell-to-cell communication and slowing the course of HD.
Axonal transport:
boosting the travel of cargo within neurons is the goal of HuntX Pharma’s therapy, in the early stages of development.
Htt lowering:
removing or preventing the build-up of huntingtin, by blocking its production at the DNA or RNA level, or clearing away the protein.
- ASOs: An antisense oligonucleotide (ASO) is a small piece of man-made genetic material that can stick to a piece of messenger RNA to prevent a protein from being made. This is one experimental method of lowering huntingtin to treat HD. Current ASOs in development by Roche, Vico, and Wave are delivered via spinal injections.
- Splice modulators: small molecules that perform a cut-and-paste within RNA, inserting a sequence that prevents the cell from making a protein. These can be taken by mouth and are in development for HD by PTC Therapeutics and Skyhawk.
- RNAi: a small piece of double-stranded RNA that can prevent the production of a protein. ExoRNA, Alnylam, and Atalanta are all working on using RNAi for huntingtin lowering.
- Gene therapy: a one-time treatment that alters or corrects a DNA sequence to treat a genetic disease.
- AAVs: a harmless virus used to package genetic material accomplishing a DNA change. This is the method used by uniQure for delivery of their HD gene therapy, as well as ones in development by Spark and Latus.
- LNPs: Lipid nanoparticles (LNPs) are a method of packaging CRISPR-based therapies for editing genes, an approach being explored by Incisive Genetics.
- Protein degraders: molecules used to break down protein clumps or to direct toxic proteins to the cell’s waste machinery. Companies like Arvinas, Alchemab Therapeutics, and Origami Therapeutics have approaches of this nature.
Companies with Approved Drugs or Ongoing Trials
Companies with Drugs Headed Toward the Clinic
