New study shows antibody therapy could offer treatment path for genetic form of ALS and FTD

Drs. Laura Ranum and Lien Nguyen

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GAINESVILLE, Fla. — New preclinical research shows promise for a potential treatment pathway aimed at slowing the disease process and extending survival in patients with ALS, often called Lou Gehrig’s disease, an insidious neurological condition.

The research by University of Florida neurogeneticists Laura Ranum, Ph.D., and Lien Nguyen, Ph.D.; Neurimmune; Biogen; and collaborators at Johns Hopkins University shows that targeting a specific mutant protein in the brain with a human-derived antibody can lower neuroinflammation, slow neurodegeneration and lengthen survival in the most common genetic form of amyotrophic lateral sclerosis, or ALS, and frontotemporal dementia, or FTD.

The mouse-model study, published online today in the journal Neuron, offers the first evidence that a novel type of immunotherapy could be a viable treatment approach for a genetic type of ALS and FTD involving repetitive DNA that produces “repeat associated non-ATG (RAN) proteins.” The study demonstrates that antibodies delivered by injection can cross the blood-brain barrier, enter cells and target the RAN proteins that build up in the brain.

The study, carried out by the UF College of Medicine’s Center for NeuroGenetics team in collaboration with investigators at biopharmaceutical companies Neurimmune and Biogen as well as Johns Hopkins University, opens a prospective new path to treating the diseases by targeting a particular pathological protein produced by a mutant C9orf72 gene.

“These proteins, which are unexpectedly produced without the normal signals for protein production, accumulate in the brains of affected individuals,” said Ranum, director of the Center for NeuroGenetics and the Kitzman Family Professor of Molecular Genetics and Microbiology. “We have tested the idea that we can use human antibodies derived from healthy elderly people to target a protein that is made from the genetic mutation. We found that by targeting one mutant protein, there is a collateral beneficial effect that results in the reduction of multiple related mutant proteins. In other words, the treatment antibody leads to the activation of a garbage disposal-like system in cells that gets rid of multiple types of proteins produced by the disease mutation.”

The study offers evidence that RAN proteins trigger motor neuron loss and other characteristics of ALS and FTD, and shows how antibodies enter cells, bind to these proteins and then haul the bad proteins away to other parts of the cell that can process and get rid of them.

“We have identified an important protein that can be targeted in the disease and found a way to attack that mutant protein to slow down and lessen the impact of disease,” Nguyen said. “This can be developed further to create a drug candidate for human clinical trials. A similar antibody-based approach may be applicable to other neurologic diseases.”

Jan Grimm, managing director and chief scientific officer of Neurimmune, said: “We are excited about the rapid progress of this collaborative project to develop human antibodies addressing the most common genetic cause of ALS and FTD. The discovery of antibodies with therapeutic potential in preclinical models is an important milestone in our quest to develop urgently needed novel therapies for these devastating diseases.”

For more information, please contact: Michelle Koidin Jaffee at or 352-273-5810.