Wave Is Developing Two Drugs That Target a Common ALS Mutation

Wave Life Sciences is developing two ALS and frontotemporal dementia therapies that target a gene mutation common in both.

The therapies target mutations of the C9orf72 gene, Wave said in a business update.

“I am excited to announce our next development program targeting C9orf72 mutations in ALS and FTD,” Dr. Paul Bolno, the company’s president and CEO, said in a press release. “With the progression of our pipeline and advancement in our [therapy] platform capabilities, we are closer to potentially bringing new hope and precision medicines to patients living with serious, genetically defined diseases.”

C9orf72 mutations are involved in 30 to 40 percent of inherited ALS cases of amyotrophic lateral sclerosis, and are risk factors in non-inherited forms. Previous studies have also linked them to earlier onset of ALS and more aggressive disease progression.

The mutation of the gene stems from a DNA problem known as the GGGGCC six-letter string expansion. While healthy people have just 20 to 30 copies of this sequence in their genes, those with the mutation can have hundreds.

This leads to the production of abnormal RNA molecules and proteins that contribute to neurological toxicity in both ALS and frontotemporal dementia, or FTD. RNA plays an important role in transmitting gene information from DNA.

Wave can use its proprietary development platform to design nucleic acid-based therapies that target molecular mechanisms or specific genetic sequences.

The company hopes to start clinical trials of its new therapies’ ability to combat ALS by the end of 2018.

Wave is also working on treatments for other genetic-based diseases, including Huntington’s and Duchenne muscular dystrophy. And it is collaborating with Pfizer on therapies for liver diseases.

“Within our discovery engine, we continue to generate compelling data for new modalities [therapy approaches] such as single-stranded RNAi [RNA interference], as well as splice correction,” Bolno said. “We recently achieved two major milestones: transitioning to a clinical stage company, with the commencement of our two Phase 1b/2a trials in Huntington’s disease, PRECISION-HD1 [NCT03225833] and PRECISION-HD2 [NCT03225846]; and the opening of our new cGMP [current good manufacturing practice] manufacturing facility.”