Target ALS is proud to announce four newly funded research projects through the In Vivo Target Validation Program, which accelerates drug discovery by supporting proof-of-concept studies in ALS-relevant mouse models. Among the 2025 grantees is Dr. Sarah Knutson of ROME Therapeutics, whose pioneering work explores a bold new therapeutic strategy: targeting LINE-1 activity to halt neuroinflammation in ALS.
A Novel Therapeutic Approach
At the heart of ROME’s project is the idea that LINE-1 retrotransposons, genetic elements normally silent in healthy cells, become overactive in ALS. This activity may fuel inflammation and DNA damage in neurons.
“We’re developing inhibitors of LINE-1 reverse transcriptase, the enzyme that drives this activity,” said Dr. Knutson. “Our compounds are designed to cross the blood-brain barrier and directly target the source of neuroinflammation.”
By blocking LINE-1 activity, her project aims to reduce disease markers in ALS models and restore healthier cellular function, potentially advancing an entirely new class of therapies.
Why Target Validation Matters
The In Vivo Target Validation Program provides researchers like Dr. Knutson with the opportunity to answer critical questions early in the development process, such as “Can experimental therapies engage their target in the brain?” and “Does that engagement meaningfully alter disease biology?”
“We’re understanding how and when LINE-1 activation can play a role in this disease,” Dr. Knutson explained. “Using our inhibitors in this model can bridge the gap between preclinical models and predicting a clinical response.”
Conducted in partnership with the contract research organization Biospective, these studies generate standardized, rigorous results that are valuable not only to the grantees but also to the broader ALS research community.
Driving Toward Patient Impact
Beyond the science, Dr. Knutson emphasized how following this novel biological connection with new perspectives is an opportunity to develop a medicine, which drives her work.
“ALS is a devastating and fast progressing disease. It’s important to remember the reality of patients living with ALS so we as scientists have that human connection with why we do drug discovery,” she said.
Her perspective underscores the power of collaboration. “What excites me is how the ALS field is very collaborative and grateful for the research efforts in this indication., It’s refreshing to see consortiums across academia, nonprofits, and biotech come together with similar ideas and diverse capabilities.”
Looking Ahead
With Target ALS support, ROME Therapeutics will test whether LINE-1 inhibitors can meaningfully impact ALS progression in mouse models. Positive results could provide the foundation for clinical development, helping bring a novel treatment approach one step closer to patients.
The In Vivo Target Validation Program exemplifies Target ALS’s commitment to advancing promising therapies toward the clinic, ensuring that bold ideas like Knutson’s have the opportunity to transform ALS research, and ultimately, patient outcomes.
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