Potential Parkinson’s Treatment, CDNF, Shows Safety and Tolerability at One Year

A potential Parkinson’s treatment called cerebral dopamine neurotrophic factor (CDNF) continues to be safe and well tolerated by patients with moderate disease using it for up to one year in a Phase 1/2 trial, and shows a promising potential to ease motor symptoms and slow disease progression, Herantis Pharma, its developer, reported.

CDNF is an investigational therapy based on a protein naturally found in the blood and cerebrospinal fluid (CSF), the liquid surrounding the brain and spinal cord.

The medication is reported to have a multi-modal mechanism of action, allowing it to tackle several mechanisms involved in Parkinson’s at once. These are thought to include lowering brain inflammation, preventing the loss of neurons, improving the workings of damaged neurons, and blocking the formation of toxic alpha-synuclein aggregates.

In preclinical studies, treatment with CDNF prevented dopamine-producing neurons — those that are gradually lost over the course of Parkinson’s — from being destroyed. CDNF was also found to be safe and effective at alleviating both motor and non-motor symptoms of Parkinson’s in rodent and primate disease models.

The safety, tolerability, and preliminary efficacy of CDNF were investigated in a Phase 1/2 trial (NCT03295786) that enrolled 17 people with moderate Parkinson’s disease. Each had five to 15 years of evident motor symptoms.

The study opened with a six-month randomized phase, in which patients were given monthly infusions of one of two doses (medium or high) of CDNF, or a placebo. This was followed by a six-month extension period, in which all were treated with CDNF each month at low or high dose, including those previously on placebo.

During the trial, CDNF was administered directly into patients’ brains through a delivery system provided by Renishaw Neuro Solutions. This system is implanted by a neurosurgeon, as CDNF cannot be delivered as a pill or injection since the body cannot transport it to the brain.

The trial’s main goal was to assess the safety and tolerability of both CDNF and its delivery system. Additional goals included measuring changes in patients’ motor symptoms using the Unified Parkinson’s Disease Rating Scale (UPDRS).

Top-line data from the first phase, reported earlier this year, showed that CDNF was safe and well tolerated in the 15 patients who completed its full six months. Patients who experienced serious side effects, thought related to “the device surgery and the drug administration process,” recovered fully and steps were taken to adjust this process.

Herantis now announced data from the study’s second and open-label part, showing that CDNF continues to be safe and well-tolerated in these 15 people. Two left the study for reasons unrelated to treatment, the company reported earlier.

Treatment emergent side effects were mild, temporary, and fewer compared to those reported in the first part of the study. Serious side effects were also less frequent.

Early 12-month efficacy data supported CDNF’s potential to ease motor symptoms and possibly slow disease progression in some patients, based on changes in their UPDRS scores at one year compared to baseline (study start) scores.

Some patients also had an increase in the levels of dopamine transporter (DaT) — a protein that regulates the flow of dopamine between neurons — visible on positron-emission tomography (PET) imaging in brain areas where CDNF was administered, suggesting an improvement in their dopaminergic function.

“In addition to the study’s favorable safety profile, it is encouraging to observe an improvement in the UPDRS motor score as well as an indication of a biological response compared to baseline, which may be clinically relevant,” Per Svenningsson, MD, PhD, professor at the Karolinska University Hospital, and the trial’s principal investigator, said in a press release.

“As this is the first clinical study of CDNF and was therefore designed primarily to examine the safety and dosing of our drug candidate, we are encouraged by the safety and tolerability we have seen so far as well as the observed improvements in some patients as measured by UPDRS and DAT PET imaging,” said Craig Cook, CEO of Herantis.

“Based on the outcome of this trial, we continue to be optimistic regarding the ongoing development of CDNF and intend to further develop and demonstrate its neuroprotective effects to make a difference in the lives of patients living with PD [Parkinson’s disease],” Cook added.

The company is analyzing data from other exploratory measures assessed during the trial, including the effects of treatment on the levels of alpha-synuclein in the CSF. These analyses are expected to be completed by year’s end.