Novel ALS therapeutic intervention shows promise in preclinical trials

Posted June 1, 2020

Mart Saarma, Ph.D., University of Helsinki
Merja Voutilainen, Ph.D., University of Helsinki

Mart Saarma, Ph.D., University of Helsinki
Dr. Mart Saarma

Merja Voutilainen, Ph.D., University of Helsinki
Dr. Merja Voutilainen

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the degeneration of the motor neurons and subsequent rapid deterioration of motor function, muscle atrophy, and eventual paralysis. There is no cure for ALS and currently therapeutic options are limited. Innovations in treatment are critical to improving the quality of life for ALS patients and their families.

In work funded by a FY17 ALSRP Therapeutic Idea Award, researchers at the University of Helsinki, Finland, led by Dr. Mart Saarma, are working to repurpose a potential Parkinson’s disease (PD) treatment for use in ALS patients since the diseases share common pathogenic mechanisms. Cerebral dopamine neurotrophic factor (CDNF) is a novel endoplasmic reticulum (ER) stress regulating protein with neurotrophic activity and a mechanism of action different from conventional neurotrophic factors. CDNF treatment has been shown to protect and restore damaged neurons in rodent models of PD more effectively than any other protein previously tested and it has shown promising topline results in the ongoing Phase 1-2 clinical in patients with PD. In order to investigate and enhance the therapeutic potential of CDNF in ALS, Drs. Saarma, Voutilainen, Sendtner and Harvey have optimized the dose and delivery system of the protein in ALS animal models. They have now been able to show that a single dose of a novel CDNF variant can increase survival and improve motor coordination in multiple ALS murine models. These treatments, or chronic infusion of this protein over time, also delayed symptom onset and protected motor neurons in the spinal cord. Importantly, these findings were observed even in the most severe animal model tested.

This work was recently published in bioRxivs (De Lorenzo, et. al., 2020) and is currently under review for peer-reviewed publication. CDNF has been granted an orphan drug status clearing the pathway for its development into a therapeutic agent for ALS. The research team is hopeful that CDNF holds great promise as a future therapeutic for ALS.



Public and Technical Abstract: Novel CDNF Variants and Optimizing Delivery in SOD1 Mouse Model: Toward Successful Clinical Trials

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Last updated Monday, January 3, 2022