Huntington’s disease: light at the end of the tunnel?
The awful thing about Huntington’s is that in most cases, people know they are going progressively lose their mind at an early age, but there is absolutely nothing they can do about it. Recently there has been tremendous excitement around suppressing toxic huntingtin production in the brain by using antisense oligonucleotides (ASOs) administered intrathecally (i.e. in the cerebrospinal fluid through the spine). Two ASOs are in full blown clinical testing: HTTRx (Ionis and Roche) which does not discriminate between mutant and normal huntingtin, and WVE-120101/2 (Wave Therapeutics and Takeda) which specifically targets mutant huntingtin. Despite encouraging testing in animal models, there are some key questions about feasibility in humans: can those drugs be reliably administered into the CSF through an invasive procedure every few weeks? will the drug stick around between doses? will there be a significant suppressive effect on the huntingtin protein? will it be safe? At least for the Ionis/Roche compound, we now have preliminary affirmative answers from a blinded placebo-controlled ascending dose trial involving 46 patients with early stage Huntington’s. The duration (<1 year) was too short to see a clinical effect but on-going phase 3 studies will show whether there is one, probably by 2022. Targeting Huntingtin Expression in Patients with Huntington’s Disease; Oligonucleotide Treatment for Huntington’s Disease (subscriber access)
Genomics is getting cheap AND fast
Identifying the microbial agent responsible for an infection tends to be a slow, low yield process: it often involves waiting for a bug which may or may not grow in a culture in the lab and then antibiotic testing takes yet more time. Serologic testing (i.e. detection of antibodies) can be quicker but is less informative. Genomic analysis has the potential to change all that and has been exploited in specific conditions using specialized molecular probes to detect a pathogen’s DNA, for instance, for TB. An alternative metagenomics approach is to simply amplify all DNA and RNA in a sample, sequence it and see what microbes surface. It has so far been hampered by expense and long processing time but this is changing. A study of 204 patients with symptoms and signs of an infection of the central nervous system demonstrates the feasibility and usefulness of this metagenomics approach to discover infectious causes of disease, with a significant number of instances where identification of the microbe and appropriate therapy would not have happened with standard methods. Turn-around is still a bit slow (1-2 weeks), but technically there is no reason this could not be reduced to 1-2 days. Soon infectious disease docs will be geneticists – or more likely this will be the job of an AI. Clinical Metagenomic Sequencing for Diagnosis of Meningitis and Encephalitis (subscriber access)
The New England Journal of Medicine is a premier weekly medical journal covering many topics of interest to the health sector. In this monthly series we offer an opinionated perspective on selected highlights that might be of interest to our clients and others.