First ‘gene silencing’ drug for Alzheimer’s disease shows promise

Effect of MAPTRx on CSF concentrations of p-tau protein and tau/Aβ42. a, The mean percentage change from baseline in p-tau over time according to dose group. b, The mean percentage change from baseline in the ratio of t-tau to Aβ42 over time according to dose group. Error bars indicate the standard error of the mean. Q4W and Q12W indicates dosing every 4 or 12 weeks, respectively. *Participants assigned to cohort A or B did not seamlessly transition to LTE part 2 and experienced a variable gap ranging from 5 to 19 months between completion of MAD part 1 at day 253 and start of LTE part 2 (D1P2). χPlacebo group was pooled. Subjects assigned to cohorts A or B and randomized to placebo had a variable gap between completion of MAD part 1 and start of LTE part 2 (D1P2).

A world-first trial at UCL and UCLH has found a new genetic therapy for Alzheimer’s disease that is able to safely and successfully lower levels of the harmful tau protein known to cause the disease. The trial, led by consultant neurologist Dr. Catherine Mummery (UCL Queen Square Institute of Neurology & the National Hospital for Neurology and Neurosurgery), represents the first time that a “gene silencing” approach has been taken in dementia and Alzheimer’s disease. The approach uses a drug called BIIB080 (/IONIS-MAPTRx), which is an antisense oligonucleotide (used to stop RNA producing a protein), to “silence” the gene coding for the tau protein-known as the microtubule-associated protein tau (MAPT) gene. This prevents the gene from being translated into the protein in a doseable and reversible way. It will also lower the production of that protein and alter the course of disease.

By University College London

Article can be accessed on: MedicalXpress