Experimental therapy could improve lifespan for patients with amyotrophic lateral sclerosis.
A stimulatory antibody may be able to reduce muscle paralysis and slow the progression of amyotrophic lateral sclerosis (ALS), according to new research published by eLife and funded by the ALS Association.
The authors discovered that the antibody was able to increase the activity of the MuSK protein, which is crucial for maintaining connectivity between motor nerves and muscles.
“The therapeutic strategy described here targets a disease mechanism, namely the loss of neuromuscular synapses, which is common to familial and sporadic forms of ALS and is based on a therapeutic antibody format with considerable clinical precedence,” said lead researcher Steven Burden, PhD.
Signaling between muscle and motor neurons plays a significant role in maintaining neuromuscular synapses and muscle health. Loss of these synapses is the precursor to motor neuron loss and is a major cause of muscle paralysis, which are hallmarks of ALS, according to the authors of the study.
Due to the crucial role of MuSK in nerve and muscle attachment, the study explored whether neuromuscular function could be preserved. The authors also investigated whether increasing MuSK activity could increase the health and lifespan of mice.
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The authors injected an MuSK-stimulatory antibody into mice models of ALS and found that the therapy reduced the detachment of motor endings from muscles. The investigators found that the antibody improved the function of the diaphragm and reduced the loss of spinal motor neurons.
Notably, treatment with the MuSK-stimulatory antibody modestly extended survival in mice.
These findings suggest that the antibody-based therapy may be an effective strategy to reduce disability and improve outcomes for human patients with ALS.
“Although the MuSK agonist antibody cannot override the many pathological pathways that occur in motor neurons and in non-neuronal cells, therapeutic interventions that preserve neuromuscular synapses have the potential to improve the quality of life for a majority of ALS patients,” Dr Burden said.
Although the FDA approved edaravone (Radicava) in May 2017 for the treatment of ALS, more work needs to be done to find a cure.