MDA 2026: New ALS platform trial adds RT1999 to speed search for treatments
Adaptive trial will screen potential ALS therapies using a blood biomarker
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- RT1999, an experimental neuroprotective therapy, will enter the EXPERTS-ALS trial for ALS.
- The trial uses a blood biomarker (NfL) to quickly screen potential ALS therapies.
- Preclinical data suggest RT1999 may improve motor neuron health and survival in ALS models.
An experimental nerve-protecting therapy called RT1999 (smilagenin) will soon be tested in people with amyotrophic lateral sclerosis (ALS) as part of a U.K. platform trial designed to quickly screen potential ALS treatments.
The study, called EXPERTS-ALS, is testing several experimental ALS therapies to determine whether they can reduce levels of neurofilament light chain (NfL), a blood marker of nerve damage. The goal is to quickly identify therapies that show early promise so they can be prioritized for future testing, helping speed the development of new ALS treatments.
Preclinical findings support testing RT1999 in ALS trial
The decision to move RT1999 into clinical testing for ALS was based in part on encouraging results from preclinical studies of the therapy in ALS models.
Scientists at Raya Therapeutic, the company developing RT1999, presented the preclinical work at this year’s Muscular Dystrophy Association (MDA) Clinical & Scientific Conference in a poster titled, “RT1999 (smilagenin): a neuroprotective neurotrophic factor modulator entering clinical development for amyotrophic lateral sclerosis (ALS).”
ALS is characterized by the degeneration and death of motor neurons, the nerve cells that control voluntary movement, leading to progressive muscle weakness and eventual paralysis. Although several therapies are approved for ALS, their benefits remain limited. This highlights the need for additional treatments that can better improve outcomes for people living with ALS.
RT1999 is a neurotrophic factor modulator, a therapy designed to increase levels of signaling molecules that help nerve cells grow and survive. The therapy is being developed to support nerve cell survival in ALS and other neurodegenerative diseases.
Poster data suggest RT1999 may help protect motor neurons
In the MDA poster, scientists at Raya reported results from laboratory studies showing that RT1999 improved motor neuron health in cell models of ALS and prevented the abnormal buildup of TDP-43 outside the nucleus, a hallmark of the disease.
The therapy also preserved motor neurons, improved motor function and strength, and prolonged survival in mouse models of ALS. In one mouse model carrying mutations in the SOD1 gene, survival was extended by 44% with RT1999 compared with untreated animals. This contrasts with a nonsignificant, 12% extension in survival with the approved ALS therapy riluzole (sold as Tiglutik and generics).
RT1999 has also been well tolerated in early studies involving healthy volunteers and people with Parkinson’s disease, the researchers said.
“These unpublished data form the basis on which RT1999 will enter the Phase 2 EXPERTS-ALS clinical trial later this year,” the researchers wrote in their abstract.
The EXPERTS-ALS study is sponsored by Sheffield Teaching Hospitals NHS Foundation Trust and funded by the U.K.’s National Institute for Health and Care Research along with several ALS-focused charities.
EXPERTS-ALS trial designed to rapidly screen potential treatments
The study aims to test between nine and 12 experimental therapies over the next five years. As an adaptive trial, new drugs can be added and evaluated while the study is ongoing and removed if predefined signs of benefit are not seen.
Three therapies are already being tested in EXPERTS-ALS: the antidiabetes drug metformin, the calcium channel blocker nifedipine, and the Parkinson’s treatment ropinirole. An experimental oral therapy called neflamapimod has also been selected for inclusion.
EXPERTS-ALS does not include a placebo arm. All participants will receive one of the study drugs for about six months. In addition to tracking NfL levels, the study will assess safety and examine how treatments affect clinical measures of ALS severity. The RT1999 arm of the trial is expected to begin before the end of this year, the researchers said.
Note: The ALS News Today team is providing live coverage of the 2026 MDA Clinical & Scientific Conference March 8-11 in Orlando, Florida. Go here to see the latest stories from the conference.
