Study proposes novel approach to slow neuromuscular degeneration in ALS patients

A study led by the Center for Biomaterials and Tissue Engineering (CBIT) of the Universitat Politècnica de València (UPV), member of Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), in collaboration with the Instituto de Investigación Sanitaria La Fe (IIS La Fe) (member of Biomedical Research Networking Center in rare diseases-CIBERER) and the University of Zaragoza (Unizar) (member of Biomedical Research Networking Center in neurodegenerative diseases-CIBERNED) proposes a novel approach to slow neuromuscular degeneration in patients with Amyotrophic Lateral Sclerosis (ALS). This pathology causes the loss of motor neurons and paralysis of skeletal muscles, and currently, there is no cure or effective treatment.

In this research, the team from UPV, CIBER BBN, IIS La Fe, and Unizar started with the hypothesis that skeletal muscle may have an active contribution to the pathology of the disease and identified skeletal muscle tissue as a therapeutic target for treating ALS.In previous studies, the UPV team demonstrated that the boron transporter NaBC1, after its activation, synergistically enhances and accelerates muscle repair.. They have corroborated its effectiveness in a mouse model of ALS, representative of the disease's familial (genetic) SOD1 variant model, which overexpresses the mutated human gene for the SOD1 protein. "This model is the most studied for conducting preclinical trials prior to human research, as it recapitulates the degeneration of lower motor neurons, and muscle denervation atrophy occurs before any evident signs of neurodegeneration," explains Patricia Rico, a researcher at CBIT-UPV.

In their study, they injected a boron-loaded alginate hydrogel - developed in the CBIT laboratories - into the quadriceps muscles of the ALS mouse model. "We found that only four injections of the treatment administered in the quadriceps of symptomatic mice significantly improved motor function.

Furthermore, hydrogels effectively reduced muscle atrophy, delaying symptoms onset and prolonging mice survival. NaBC1 activation enhanced muscle repair processes, resulting in the reduction of several pathological features in muscles affected by ALS and a decrease in muscle inflammation along with the activation of essential muscle metabolic pathways," highlights Patricia Rico.

Moreover, the UPV, CIBER BBN, and IIS La Fe team found that the recovery of muscular pathology had a retrograde neuroprotective effect, modulating neuroinflammation and mitigating motor neuron loss.

These findings are highly relevant for understanding the influence of muscle tissue on ALS progression and confirm the suitability of establishing skeletal muscle as a therapeutic target. With our study, we propose a novel approach to slow down neuromuscular degeneration in ALS, which could complement existing therapies targeting motor neuron death. A possible combined therapy of treatments targeting motor neuron inflammation together with treatments targeting muscle regeneration could have a greater chance of success in extending and improving the quality of life of patients suffering from this terrible disease."

Juan Francisco Vázquez, researcher at IIS La Fe and coordinator of the ALS Unit at Hospital la Fe

Currently, the team of researchers are evaluating in the same ALS mouse model, SOD1, a boron compound drug, to propose its repositioning targeting muscle with a different application from its original indication.

"If the results with this drug are positive, the new therapeutic indication could be the regeneration of skeletal muscle. The repositioning of this drug would represent a significant advance in the regulatory pathway and a great advantage for its use in clinical trials, reducing the time to reach ALS patients", emphasizes Dr. Vázquez.

Donation from the StopELA Association

The work led by the UPV has aroused the interest of the StopELA Patients' Association, which has donated to contribute to this research's progress. Specifically, the donation will go to the recruitment of a student who will do his doctoral thesis under the coordination of Patricia Rico and Juan Francisco Vázquez, neurologist coordinator of the Motor Neuron Diseases Unit at the Hospital Universitari i Politècnica La Fe de València.

StopELA was born in 2019 as an educational project of the Sant Cristófor Mártir school in Picassent. One of the school's teachers, José Eduardo Rubio, who died of the disease, launched together with his wife, Fran Ferrer, and with the support of the educational community, friends, family, relatives, and the majority of the town, a great wave of solidarity and activities to raise awareness in society about ALS and the need for research.

Thanks to the sale of wristbands and the celebration of sporting and cultural events, the StopELA Association has since raised 70,000 euros to help fund the project of the Research Group in Neuromuscular Pathology and Ataxias of IIS La Fe. The StopELA Association continues its work to raise awareness and support for research by selling solidarity key chains and voluntary contributions from members.