Neuroprotective therapy for amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) or Lou Gehrig's disease is one of the most common neuromuscular diseases worldwide and characterized by rapidly progressive weakness and muscle atrophy throughout the body. Until now, there is only one FDA-approved treatment that has been found to improve survival but only to a modest extent. Riluzole, however, does not reverse the damage already done to motor neurons, and people taking it must be monitored for liver damage. Thus, there is a high unmet clinical need for new therapy approaches. One or two out of 100,000 people develop ALS each year in the US, hence it is an orphan drug disease. Scientists at the University of Göttingen developed a novel therapeutic approach, which shows a significant prolonged survival and clear neuroprotective effects in the widely used pre-clinical SOD mouse model.

Challenge

Until now, there is only one FDA-approved treatment with Riluzole (Rilutek) that has been found to improve survival but only to a modest extent. Riluzole, however, does not reverse the damage already done to motor neurons, and people taking it must be monitored for liver damage. Thus, there is a high unmet clinical need for new therapeutical approaches.

Our Solution

Scientists at the University of Göttingen developed a new therapeutic approach for ALS based on early neuroprotective mode of action: significant prolonged survival and clear neuroprotective effects.

Survival is significantly prolonged in ALS mice treated in early phase of disease. Kaplan-Meier survival plot for age at death in SOD1G93A mice, the "gold standard" for screening ALS compounds. Source: Dr. Lars Tönges.

Advantages

• Novel therapeutic approach: early treatment with neuroprotective and possible regenerative effects.
• Compound is non-toxic and already clinically tested.
• Oral application of compound.
• In vivo Proof of Concept in the “gold standard” preclinical ALS mouse model successfully achieved:
  • Prolonged survival.
  • Improved motor coordination.
  • Clear signs of motoneuron protection: increased survival of spinal cord motoneurons and a decreased astrogliotic infiltration.

Applications

New neuroprotective and neuroregenerative therapy for ALS.

Developmental Status

Currently in first clinical trial.

Patent Status

Granted IP: US9980972B2, EP2825175B1 (validated in DE, FR, GB, IT, ES, AT, CH, FI, NL, SE, IE, DK, NO). Patent Owner: University of Göttingen public law foundation.

References

Tönges et al.: Rho kinase inhibition modulates microglia activation and improves survival in a model of amyotrophic lateral sclerosis. Glia 2014;62(2):217-32.
Günther et al.: Rho Kinase Inhibition with Fasudil in the SOD1G93A Mouse Model of Amyotrophic Lateral Sclerosis-Symptomatic Treatment Potential after Disease Onset. Front Pharmacol. 2017;8:17.

Our data have been independently verified by Takata et al.:
Fasudil, a rho kinase inhibitor, limits motor neuron loss in experimental models of amyotrophic lateral sclerosis. Br J Pharmacol. (2013) 170(2):341-51.

Contact

Dr. Stefan Uhle
Patent Manager Life Science
E-Mail: suhle(at)sciencebridge.de
Tel.: +49 551 30724 154
Reference: BioC-1198-UMG

Tags: Therapy