JAMA Neuro: Is the lipid-lowering drug simvastatin expected to be a disease-modifying treatment for patients with Parkinson's disease?

Current treatments can control the symptoms of Parkinson's disease (PD), but there are no known treatments that can slow the progression of
the disease.
Preclinical and epidemiological studies support the potential use
of statins as disease-modifying therapies.
To this end, this study aimed to determine whether simvastatin has the potential as a disease-modifying therapy
for patients with moderate Parkinson's disease.

This randomised clinical trial was a double-blind, parallel-group, placebo-controlled, inactive trial conducted
in 23 UK National Health Service Trusts from March 2016 to May 2020.
The included participants were aged between 40 and 90 years and diagnosed with idiopathic PD, with a modified Hoehn-Yahr stage ≤ 3.
0
during medication.
Assigned 1:1 to simvastatin or matched placebo by computer-generated random sequences, stratified
by site and Hoehn-Yahr stage.
In the simvastatin group, participants entered a 1-month simvastatin phase of 40 mg per day, followed by a 23-month simvastatin of 80 mg per day, followed by a 2-month washout period
.

The pre-specified primary outcome was a 24-month change in MDS-UPDRS Part III scores (a high score indicates a worse outcome).

The primary ineffectiveness analysis included participants
who started the 80 mg phase with valid primary outcome data.
The safety analysis included all participants who started the trial treatment, reported
by dose at the time of the event.

The results showed that of the 332 patients who were evaluated for eligibility, 32 refused and 65 were ineligible
.
Of the 235 participants recruited, 97 (41%) were female and 233 (99%) were white, with an average (SD) age of 65.
4 (9.
4) years
.
A total of 216 patients progressed to a dose
of 80 mg.
Analysis of primary outcomes (n = 178) showed an additional deterioration in the MDS-UPDRS III score (1.
52 points; bilateral 80% CI, -0.
77 to 3.
80; unilateral ineffectiveness test P = .
006) when simvastatin was not dosed for 24 months compared with placebo.

Participants receiving 0 mg simvastatin reported a total of 37 serious adverse events (AEs), including 3 deaths, and 171 AEs; Participants who received either 40 mg or 80 mg of simvastatin reported a total of 37 severe AEs and 150 cases of AEs
.
Four participants withdrew from the trial
due to AEs.

In this randomized clinical trial, simvastatin failed
as a disease-modifying therapy for patients with moderate PD.

References:

Evaluation of Simvastatin as a Disease-Modifying Treatment for Patients With Parkinson Disease: A Randomized Clinical Trial.
JAMA Neurol.
Published online October 31, 2022.
doi:10.
1001/jamaneurol.
2022.
3718