Treatment Opportunities for Patients With ALS and FTD: Merit Cudkowicz, MD, MSc

Following the commencement of a study exploring WVE-004, an investigational treatment for C9-ALS and C9-FTD, the director of the Sean M. Healey & AMG Center for ALS discussed the clinical implications and the treatment’s potential.

“Right now, we don’t have any treatments that cure or significantly slow the progression in people with this form of ALS, [with] C9orf72, and we certainly don’t have anything for the people with this mutation and dementia either. This has huge potential because it’s right on [the] disease-causing mutation to make an impact on people’s function, both cognitively and motor skills.”

With dosing of WVE-004, an investigational treatment for patients with C9orf72-associated amyotrophic lateral sclerosis (C9-ALS) and frontotemporal dementia (C9-FTD), recently beginning in the phase 1b/2a FOCUS-C9 trial (NCT04931862), the chair of the trial’s clinical advisory board, Merit Cudkowicz, MD, MSc, spoke with NeurologyLive on the potential impact for patients.

The absence of treatment options for patients with C9-FTD and C9-ALS remains an issue, according to Cudkowicz, who outlined WVE-004’s mechanism of action and its role in these diseases. The treatment targets the expansion of G4C2 in C9orf72, which leads to accumulation of abnormally translated dipeptide repeat proteins (DPRs) and a lowering of C9orf72 protein levels. WVE-004 targets the expansion, lowering the amount of DPRs without affecting healthy proteins, which investigators hope will “reduce toxicity of the mutation,” further leading to clinical efficacy.

Cudkowicz, who is also director of the Sean M. Healey & AMG Center for ALS and chief of neurology at Massachusetts General Hospital, further commented on the potential for WVE-004, which was developed by Wave Life Sciences, to be used in the prevention phase for C9-ALS and C9-FTD, pending evaluations of safety and efficacy.