Add-on Azilect leads to greater clinical gains than levodopa alone

Treatment tied to reductions in Hcy, IGF-1 elevations

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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A year of treatment with levodopa plus benserazide led to greater clinical improvements among Parkinson’s disease patients who were also using add-on Azilect (rasagiline), according to a small Chinese study.

The use of Azilect was also associated with greater reductions in homocysteine (Hcy), a biomarker associated with disease progression, and elevations in insulin-like growth factor (IGF-1), a neuroprotective molecule.

The study, “Effects of rasagiline combined with levodopa and benserazide hydrochloride on motor function and homocysteine and IGF-1 levels in elderly patients with Parkinson’s disease,” was published in BMC Neurology.

To combat the loss of the brain signaling chemical dopamine that characterizes Parkinson’s disease, patients are treated with levodopa, which provides them with a precursor molecule to generate more dopamine.

Levodopa is usually combined with other molecules to help prevent it from breaking down, allowing more of it to reach the brain where it’s needed. Benserazide is used outside the U.S. In the U.S., where benserazide is not approved, carbidopa is typically used.

Certain add-on therapies are also sometimes used to help combat motor fluctuations, or periods of motor symptom worsening that emerge as the effects of levodopa wear off between doses. One is Azilect, which inhibits an enzyme that normally degrades dopamine, extending the time levodopa is active.

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Azilect use with levodopa treatment

In this study, scientists analyzed the real-world effects of adding Azilect to a levodopa/benserazide treatment regimen among middle to late-stage Parkinson’s patients, ages 60 and older, at a hospital in China.

A year’s worth of data from 64 patients treated with levodopa/benserazide were analyzed, including from 32 people also given Azilect. Patients in the Azilect group (18 men, 14 women) had a mean age of 69.4 and had been living with Parkinson’s for a mean of 7.2 years. The characteristics in the group that didn’t take Azilect were similar.

The Azilect group was given the add-on oral therapy at a dose of 1 mg per day along with a stable levodopa/benserazide regimen. All the participants also received a rehabilitation therapy program.

The total rate of clinical efficacy was significantly higher in the Azilect group after a year of treatment compared with the control group (93.75% vs. 68.75%). The total effective rate was defined as patients who saw improvements in muscle tone and motor function, and who could assist in or carry out daily life activities.

Motor symptom severity, as assessed by the Hoehn and Yahr Stage and Movement Disorders Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part III, was similar between the two groups at the start of treatment and improved in both after a year. Those in the Azilect group saw greater improvements, however, with significantly lower scores on both scales than the controls after a year.

Blood levels of Hcy were significantly lower and IGF-1 significantly higher in the Azilect group than the controls after a year, where levels had been similar before starting therapy. Still, both groups generally saw improvements in these measures after a year.

Higher levels of Hcy are believed to be toxic to nerve cells and have been linked to cognitive and motor dysfunction, as well as motor fluctuations and dyskinesia, or involuntary movements, in Parkinson’s. IGF-1 is critical for nerve cell survival and brain health. Reduced functionality of IGF-1 has been observed in Parkinson’s patients and is linked to disease progression and cognitive declines.

These biomarker changes may indicate the protection of dopamine-producing nerve cells with Azilect, according to the researchers.

The study indicates “relative to levodopa therapy alone, the addition of [Azilect] … is more effective in improving the motor function of patients with Parkinson’s disease,” wrote the researchers, who noted that clinical follow-up is needed, given the small size of the study.