Objective: To develop a novel disease-modifying therapy in Parkinson’s disease (PD) that affects both motor and non-motor symptoms, based on a novel stress-protective protein CDNF.

Background: CDNF is a member of a novel family of unconventional neurotrophic factors which – despite the similar name – has very little in common with GDNF. CDNF protects midbrain dopaminergic neurons and improves both motor and non-motor functions in rodent and primate models of PD via a mechanism of action distinct from any other known growth factor-like protein. A novel therapy for PD is currently being developed based on intracerebral infusion of recombinant human CDNF protein. Previous failures of neurotrophic factors in phase II trials have provided important information on how to improve brain infusion of therapeutic proteins. Characteristics and location of infusion catheters, infusion protocol and the distribution properties of the therapeutic protein are among the key determinants of efficacy of an intracerebral protein therapy.

Methods: A phase I-II clinical study with a goal to enroll 18 patients with idiopathic PD of moderate severity is on-going. A surgically implanted drug delivery system (DDS; developed by Renishaw Plc, a co-sponsor of the study), capable of intermittent intracerebral protein drug delivery will be used in this first-in-human study with CDNF. A placebo-controlled clinical long-term study design, including cross-over to CDNF after six months of treatment, will be used for assessment of safety and tolerability of the treatment (primary endpoint), as well as for preliminary assessment of CDNF’s effects on motor function (UPDRS) and activity of the nigrostriatal dopamine pathway (DAT-PET). In addition, data will be collected on the safety and functionality of the DDS.

Results: First PD patients have been implanted with the DDS and dosed with rhCDNF in early 2018. Preclinical development challenges, clinical study design and preliminary safety findings will be discussed.

Conclusions: Based on preclinical data, rhCDNF has robust regenerative effects in the midbrain and improves both motor and non-motor symptoms of PD. The state-of-the-art brain delivery method used in the clinical study and the physicochemical properties of the rhCDNF allow optimal distribution of the drug in the target brain area, and will thus allow proper assessment of the pharmacodynamic properties of rhCDNF in PD patients.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/a-first-in-human-clinical-study-to-test-the-safety-and-preliminary-efficacy-of-cdnf-in-parkinsons-disease/