Clinical Trials

Date: 2017-12-11

Type of information: Presentation of results at a congress

phase: preclinical

Announcement: presentation of results at 28th International Symposium on ALS/MND

Company: Wave LIfe Sciences (USA - MA)

Product: WVE-3972-01

Action mechanism: antisense oligonucleotide.

Disease: amyotrophic lateral sclerosis (ALS) frontotemporal dementia (FTD)

Therapeutic area: Rare diseases - Genetic diseases - Neurological diseases - Neurodegenerative diseases

Country:

Trial details:

Latest news:

• • On December 11, 2017, Wave Life Sciences announced data from preclinical studies of WVE-3972-01, the company’s investigational stereopure antisense oligonucleotide designed to target the pathogenic allele of the C9ORF72 gene for the treatment of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). In preclinical studies, WVE-3972-01 demonstrated substantial reduction in disease-associated biomarkers and superior potency to stereorandom oligonucleotides. Wave Life Sciences intends to initiate clinical trials of WVE-3972-01 in ALS and FTD in Q4 2018.
• Data from in vitro and in vivo studies of stereorandom and stereopure oligonucleotides, including WVE-3972-01, were presented by Robert Brown, Jr., DPhil, MD at the 28th International Symposium on ALS/MND in Boston during the closing plenary session on December 10, 2017. Dr. Brown is Chair and Professor of Neurology at the University of Massachusetts Medical School.
• Mutations in the C9ORF72 gene are believed to be the most common cause of familial ALS and FTD. These mutations cause the production of repeat-containing transcripts, resulting in accumulation of RNA foci and an increase in dipeptide repeat proteins in the brain and spinal cord. C9ORF72-associated diseases such as familial ALS and FTD are postulated to arise from a reduction of normal C9orf72 protein or a gain in toxic RNA foci or dipeptide repeat proteins.
• Wave Life Sciences, in collaboration with Dr. Brown and his team, showed that WVE-3972-01 preferentially reduced repeat-containing transcripts versus all transcripts in neurons derived from ALS patients with a C9ORF72 mutation and demonstrated greater potency when compared with stereorandom oligonucleotides of the same sequence. In vivo studies conducted in a transgenic animal model containing the mutated C9ORF72 gene demonstrated that WVE-3972-01 produced a significant and sustained preferential knockdown of repeat-containing transcripts, RNA foci and dipeptide repeat proteins without altering total C9orf72 protein levels. When measured at eight weeks after treatment, RNA foci in the spinal cord were reduced by 70%. Dipeptide repeat proteins achieved a maximum reduction of 76% and 87% in the spinal cord and the cortex, respectively, and remained significantly low through eight weeks, the last observed time point.

   

Is general: Yes