Gene therapy for overexpressing Neuregulin 1 promotes functional improvement in the SOD1 ALS mice

In two recently published papers, members of the Group NP&R showed that overexpression of Neuregulin 1, mediated by gene therapy, improved the evolution of the disease in the SOD1G93A mouse model of Amyotrophic Lateral Sclerosis (ALS). They suggest that this therapy could be considered in the future as a treatment for ALS.

In the first, an AAV vector was injected intravascularly to increase NRG1-type I in the mouse muscles. The results showed that SOD1G93A mice with higher levels of NRG1-I began to develop symptoms of the disease later, and had a slower disease progression than the controls. In addition, this therapy promoted an increase of the number of surviving motoneurons in the spinal cord compared to control mice, as well as improved preservation of their connections with skeletal muscles.

Mòdol-Caballero G, et al. Gene therapy for overexpressing Neuregulin 1 type I in skeletal muscles promotes functional improvement in the SOD1(G93A) ALS mice. Neurobiol Dis 2020; 137:104793. doi: 10.1016/j.nbd.2020.104793.

In the second paper, we used gene therapy based on intrathecal administration of AAV virus to overexpress NRG1-III in the spinal cord of SOD1G93A mice. Our results indicate that overexpression of NRG1-III preserved neuromuscular function of the hindlimbs, improved locomotor performance, increased the number of surviving MNs, and reduced glial reactivity in the treated female SOD1G93A mice. However, NRG1-III did not have a significant effect on male mice, indicating relevant sex differences.

Mòdol-Caballero G, et al. Therapeutic role of Neuregulin 1 Type III in SOD1-linked Amyotrophic Lateral Sclerosis. Neurotherapeutics 2020 in press. doi: 10.1007/s13311-019-00811-7.

Project funded to develop a new treatment to stop ALS

The project lead by Rubén López-Vales, from the Group NPiR, entitled "A new treatment to stop the progression of amyotrophic lateral sclerosis (ALS)", will investigate the contribution of a new family of lipids to modulate neuroinflammation in mice with ALS, looking for a new therapy that will be more effective than the current ones. The objective is to stop the progression of ALS and find new biomarkers that predict their evolution.

The project has been selected, after a rigorous selection process with the participation of more than 250 experts, and will receive a maximum of 500,000 euros, which will be provided by the "La Caixa" Foundation and the Luzón Foundation.

NeuroHeal Biomedicals, a new technology-based company to develop a new treatment for peripheral nerve damage

NeuroHeal Biomedicals, a new technology-based company to develop a new treatment for peripheral nerve damage

The research team led by Dr. Caty Casas, from the Institute of Neurosciences of the Universitat Autònoma de Barcelona (INc-UAB), has created the company NeuroHeal Biomedicals to develop a new neuroprotective treatment that also accelerates the regeneration of damaged peripheral nerves.

The peripheral nerves allow us to perform all daily activities, such as walking, running, catching, hugging or feeling. There are several types of injuries that peripheral nerves can suffer due to trauma, infection, metabolic or inherited problems or exposure to toxins. For example, some injuries can happen after a violent accident, through the section of the nerves of the hand, but also by complications, such as hernias or carpal tunnel syndrome. Common symptoms include tingling, numbness and pain and, in the most severe cases, loss of sensory, motor or autonomic nervous function.

NeuroHeal, the drug proposed by the research team, is a combination of two active ingredients and has been designed to encourage neurons to conveniently activate their own endogenous mechanisms of neuroprotection and nerve regeneration; among them a fine-tuned activation of autophagy. The team innovated a platform to discover NeuroHeal based on the use of systems biology approaches and machine learning.

"Preclinical trials developed so far have shown that NeuroHeal exerts neuroprotective effect on spinal motor neurons after peripheral nerve injury and it reduces the damage-associated microgliosis involved in neuropathic pain apparition. In addition, it accelerates nerve regeneration, and reduces muscle atrophy due to denervation, improving functional recovery in animal models with peripheral nerve damage, "explains Caty Casas, project leader.

To reach these results and non-regulatory preclinical development, which demonstrate a lack of toxicity, there has been public and private financial support: from the Knowledge Industry Aid of the Agencia de la Gestió d'Ajuts Universitaris i de Recerca ( AGAUR) of the Generalitat de Catalunya, the investment of GENESIS Ventures, La Marató de TV3 and the Spanish Ministry of Economy and Competitiveness.

In addition, this was the first project funded by the new GENESIS Ventures fund, and according to José Luis Falcó, CEO of this company "we are very happy to have invested in this promising project, even before it became a biotech-based company . Now we see it constituted and as the first success story of our vehicle". 

The research team has already patented the new drug. Now the company's aspiration is to complete the regulatory preclinical phase and move forward to conduct clinical studies in humans. "The development of a medicine is a long road, but we hope to start phase I trials in 2022 and move forward with this new therapy," says Caty Casas.

Group of Neuroplasticity and Regeneration

The research activities of the Group focus on the study of physiopathological mechanisms of neural lesions, neuropathic pain and neurodegeneration, and on the application of novel therapeutic strategies for regenerating traumatic and degenerative lesions of the nervous system.

The members of the group have combined expertise in microsurgery, neurophysiology, rehabilitation, morphology, cell culture, cellular and molecular neurobiology, bioelectronics and immunology.

The group has established cooperative research in clinical neurosciences, particularly on new nerve repair therapies with the Hospital Clinic of Barcelona, in modulation of neural plasticity after brain and spinal cord lesions with the Institute Guttmann of Neurorehabilitation, and in motoneuron diseases and neuropathies with the Hospital of Bellvitge.

Which are the research lines of the group?

What can the group offer?