The incidence of Parkinson's disease appears to be increasing rapidly worldwide. To date, around 300,000 people in Italy are affected. Although muscle rigidity is a cardinal sign of the disease - along with bradykinesia, or the slowing of voluntary movements, and tremor - this symptom remains poorly understood.

Levodopa, considered the 'miracle' drug for treating Parkinson's disease, is still the most effective treatment for managing the motor symptoms of the disease. However, to date, there have been no trials that have objectively evaluated and clarified the effect of dopaminergic therapy on muscle stiffness in PD patients.

The study, coordinated by Antonio Suppa of the Department of Human Neuroscience at Sapienza University of Rome in collaboration with IRCCS Neuromed, aims to fill this gap. To clarify the effect of levodopa on muscle rigidity in Parkinson's patients, the research team used an innovative experimental approach combining robotic instrumentation and non-invasive neurophysiological measurements. This methodological approach made it possible to precisely reconstruct the mechanisms underlying muscle rigidity, thus enabling a more accurate description of the pathophysiological basis of muscle rigidity in Parkinson's disease.

To investigate the efficacy of the treatment, the motor signs and symptoms of the disease in patients were assessed both in a pharmacological OFF state (at least 12 hours after the last intake of the usual dose of levodopa) and in a pharmacological ON state (at least 1-2 hours after taking the drug).

"We have shown that muscle rigidity depends on a specific reflex, the long-latency stretch reflex (LLR), which is altered in Parkinson's disease patients", says Antonio Suppa, Professor at Sapienza University. Levodopa has been shown to significantly reduce this abnormality by restoring more physiological activation patterns".

Based on their findings, the researchers hypothesised and described a new neural circuit responsible for Parkinson's disease rigidity, linking the brainstem, cerebellum and spinal cord. This circuit is affected by dopamine and could be the starting point for new therapies.

Research into muscle rigidity is still ongoing and is one of the main topics of the new Laboratory of Experimental Neurology, Neuroengineering, and Telemedicine at Sapienza University. By providing an objective and detailed demonstration of the mechanisms by which levodopa acts to reduce muscle rigidity in patients, the study is an important scientific reference on the subject. Furthermore, the identification of the possible neural circuit underlying the muscle rigidity that is sensitive to dopaminergic stimulation opens up avenues for innovative therapies.

References:

Falletti M, Asci F, Zampogna A, Patera M, Pinola G, Centonze D, Hallett M, Rothwell J, Suppa A.Rigidity in Parkinson's Disease: The Objective Effect of Levodopa. Mov Disord. 2025 Jan 8. doi: 10.1002/mds.30114. Epub ahead of print. PMID: 39777428.

Further Information:

Antonio Suppa

Department of Human Neuroscience

antonio.suppa@uniroma1.it