Amyotrophic Lateral Sclerosis (ALS) is a devastating and fatal neurodegenerative disease affecting motor neurons, leading to progressive paralysis. With a lifetime risk of 1:400 and no effective treatment available, there is an urgent need for novel therapeutic strategies to slow disease progression and improve patient outcomes.

OUR SOLUTION
We have identified miR126-5p as a novel gene therapy target for ALS. miR126-5p plays a crucial protective role in motor neurons and muscles, counteracting toxic signals that contribute to neurodegeneration. Our RNA-based therapy aims to restore miR126-5p levels, protecting motor neuron axons, improving muscle contraction, and delaying paralysis.

miR-126 5p beneficial effect in ALS disease. A) In a non-cell autonomous process, muscle and MN communication is alter in ALS disease. Downregulation of miR126-5p promote axon degeneration, NMJ disruption and cell death by regulating muscle

TECHNOLOGY & MECHANISM OF ACTION
Our approach leverages miR126-5p overexpression to restore neuroprotection and prevent ALS progression by:
Extending motor neuron survival and axonal growth in ALS models.
Preserving neuromuscular junction (NMJ) function, reducing denervation, and enhancing muscle contraction.
Inhibiting toxic signaling pathways, preventing TDP-43 mislocalization and aggregation, a hallmark of ALS pathology.

(A) Diseased muscles promote axon degeneration and NMJ disruption by secreting toxic factors that impair motor neuron survival.
(B) The formation of the CRMP4-dynein complex is enhanced in ALS, driving neuronal loss through altered retrograde signaling.
(C) Muscle-derived exosomes normally transport miR-126-5p to NMJs, where it regulates TDP-43 mRNA translation in presynaptic axons.

DEVELOPMENT STATUS
In vitro validation: miR126-5p overexpression in ALS-diseased neurons extended axonal growth and preserved muscle contraction in a proprietary microfluidic “lab-on-a-chip” co-culture platform.
In vivo validation: Intramuscular injection of miR126-5p in ALS mouse models rescued muscle denervation, improved motor function, and delayed paralysis progression.
Mechanistic insights: Our research has elucidated the neuroprotective effects of miR126-5p, demonstrating its potential as a disease-modifying therapy for ALS.

INTELLECTUAL PROPERTY
Patent: PCT/IL2019/050545 – miR126-5p for Treating Motor Neuron Diseases.
National Phase: USA & Europe.