The Science Advisory Council enthusiastically embraced the work of Healey Center for ALS faculty Mark Albers, MD, PhD, who discovered a new mechanism that damages nerve cells and triggers an inflammatory response in people with ALS and those with Alzheimer’s disease (AD). Based on this work, Dr. Albers and the Healey Center Trial Design Team designed a trial to test a promising therapeutic, baricitinib, with the potential to treat individuals with either ALS or Alzheimer’s disease. This will be the first time a therapy is tested in two neurodegenerative disorders at once (called a basket trial).

Inflammation is a key indicator of viral infections, and, in the case of ALS and AD, also plays a crucial role in neuronal death. A primary feature of many viral infections is cytoplasmic double-stranded RNA (cdsRNA). Dr. Albers and his team’s new discovery is that cdsRNAs are present in 97% of patients with ALS (both sporadic and familial) and in approximately 50% of patients with sporadic AD. The Albers Lab discovered that inflammation in ALS and AD is not solely caused by viral infections, but is also the result of a genomic lesions expressing RNA that forms cdsRNA.

Janus kinase inhibitors (JAK inhibitors) are a type of medication that interfere with the signaling pathway that causes inflammation from these cdsRNAs in ALS and AD. Several JAK inhibitors, including baricitinib, are FDA-approved and are used successfully to treat some cancers and rheumatoid arthritis.

Working collaboratively with Mass General’s Healey Center for ALS and Mass General’s Interdisciplinary Brain Center, the team analyzed cerebral spinal fluids from both patients with ALS and AD. Through this work they identified a panel of inflammatory and neuronal death biomarkers in the cerebrospinal fluids that are elevated in both ALS and AD patients.

The Neurodegenerative Alzheimer’s disease and ALS (NADALS) basket trial will test the impact of baricitinib on reducing the levels of inflammation in individuals with ALS and individuals with Alzheimer’s disease. Dr. Albers and his team will use the biomarkers that were identified to measure the amount of inflammation and neuronal death reduction as well as an unbiased discovery program to identify new biomarkers that are drug responsive. The data gathered in this initial trial will provide key information needed before this drug enters the Platform Trial for ALS.