Vaccination is said to be alpha-synuclein from the brain …

/ Kateryna_Kon – stock.adobe.com

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Vienna – Repeated vaccination against the protein alpha-synuclein, the deposits of which in the brain are said to be involved in the pathogenesis of Parkinson’s disease, has induced the formation of antibodies in patients in the early stages of the disease, and according to the report in Lancet Neurology (2020; DOI: 10.1016 / S1474-4422 (20) 30136-8) the cerebrospinal fluid concentration of alpha-synuclein was reduced.

Alpha-synuclein is the main component of Lewy bodies that occur in Parkinson’s disease and related diseases in the nerve cells and may be involved in their downfall. The elimination of alpha-synuclein (or the prevention of further deposits) could therefore favorably influence the course of the disease.

An Austrian biotechnology company has developed a vaccine for this purpose. It is an antigenic peptide that contains a short section of alpha-synuclein and is said to induce the formation of antibodies after injection. These antibodies are then supposed to neutralize alpha-synuclein in the brain. The effect would be the same as with treatment with monoclonal antibodies, which have been tried in Alzheimer’s disease for years in larger clinical studies (however so far unsuccessful).

Parkinson’s vaccine PD01A has been tested in recent years in a phase 1 study in 32 patients with early-stage Parkinson’s disease where the protective effect of the treatment is most likely to be expected.

Participants were initially randomized to 4 subcutaneous vaccinations in 2 different doses of PD01A. As the team led by Günther Staffler from the manufacturer AFFiRiS from Vienna reported, antibodies against alpha-synuclein were formed, the titer of which decreased again in the course of the first year. The patients therefore received a first refresher after 116 weeks and another booster after 150 weeks.

In this way it was possible to keep the antibody titer at a level for at least 3.5 years, which could create the prerequisites for a disease-modifying effect. According to the publication, there have been no serious complications that would jeopardize the continuation of clinical development.

The most common side effects were local reactions at the injection site. Systemic side effects were fatigue in 4 patients, headache in 3 patients, myalgia in 3 patients, muscle stiffness in 2 patients and tremor in 2 patients.

Patients receiving the higher vaccine dose experienced a 51% decrease in cerebrospinal fluid alpha-synuclein concentration. According to the publication, it correlated with a favorable development of symptoms in the UPDRS (“Unified Parkinson’s Disease Rating Scale”), a scale for monitoring the course of Parkinson’s disease.

However, the vaccination could not stop the disease. In the course of the study, the patients had to increase the dosage of the medication from 355 mg to 587 mg L-dopa (equivalence). The manufacturer announced the continuation of the clinical trial with a phase 2 study. © rme / aerzteblatt.de

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