Resting tremor, one of the most recognizable but also most enigmatic symptoms of Parkinson's disease, may have found a new enemy: a targeted therapy. This is suggested by an innovative study (link here) that has put the spotlight on caudate nucleus1 and on its dopamine content as a possible therapeutic target.
A perspective that overturns traditional beliefs about the role of dopamine in motor symptoms and opens up new scenarios for more precise and personalized treatments. The research lifts the veil on a future in which “one-size-fits-all” therapies could give way to strategies tailored to each patient.
A new light on Parkinsonian tremor
The study, conducted by researchers at the Champalimaud Centre in Lisbon and published in the journal npj parkinson's disease (I link it here), analyzed data from over 500 patients with Parkinson's disease. The aim was to shed light on the complex relationship between resting tremor, one of the cardinal symptoms of the disease, and the dopamine, the key neurotransmitter involved in movement control.
Until yesterday it was believed that the loss of dopamine in brain areas such as the whore2 was primarily responsible for the motor symptoms of the disease. However, the researchers found that, paradoxically, patients with resting tremor had greater preservation of dopamine in the caudate nucleus, a brain region important for movement planning and cognitive function.
An innovative approach to the study of tremor
To reach these conclusions, the research team used a multidisciplinary approach that combined clinical evaluations, Single photon emission computed tomography (SPECT) brain imaging to visualize dopamine neurons, and wearable motion sensors to accurately measure the severity of the tremor.
These sensors have proven to be a valuable tool for obtaining objective measurements of tremor, which are often difficult to capture with traditional clinical assessment scales. Thanks to these devices, researchers they were able to reliably link the symptoms with the underlying neural processes.
Towards a more precise classification of the disease
This study follows on from previous research by the same team, which had already highlighted the importance of treating resting tremor separately from other motor symptoms. A discovery that challenges the traditional approach that tended to consider these symptoms as an indistinct whole.
That research had in fact revealed that resting tremor varies depending on the type of progression of the disease: it is more common in patients with “brain-first” Parkinson’s, in which the pathological process begins in the brain, while it is less frequent in those with “gut-first” Parkinson’s, where the disease begins in the intestine and then spreads to the brain.
Waiting for a targeted therapy
For Joaquim Alves da Silva, senior author of the study and head of the neuroscience laboratory that conducted the research, these results pave the way for a paradigm shift in the treatment of Parkinson's disease.
The loss of dopamine in the Parkinson is not uniform: different patients may lose dopamine in distinct circuits. By focusing on resting tremor in isolation, we are in a better position to identify the specific neural pathways involved. For example, could tremor arise from a dopamine imbalance between the caudate nucleus and the putamen? Identifying reliable biological correlates of individual symptoms is critical, because it paves the way for targeted therapy to alleviate them.
A perspective shared by the first author of the study, Marcelo Mendonca:
Not all dopamine cells are the same. They have different genetic profiles, connections, and functions. This means that the cells a patient loses or retains could influence their symptoms. For example, tremor could be linked to the loss or preservation of specific dopamine populations that connect to certain brain areas. This variation in cell type loss could further explain the wide range of symptoms among Parkinson's patients.
The Future of Parkinson's Research
The research team is already looking to the future. The goal is to establish a causal link between the preservation of dopamine in the caudate nucleus and resting tremor, a difficult task to achieve in humans. To this end, the researchers plan to test this hypothesis in animal models, where it is possible to manipulate specific cells and observe their effects on tremor.
Additionally, the use of advanced imaging techniques, such as high-resolution dopamine PET and MRI, could help identify key nodes in the dopamine system and link them to specific motor symptoms. This approach could shed light on why Parkinson's symptoms vary so much from patient to patient.
In conclusion, this research highlights the importance of going beyond general classifications in Parkinson's disease and underscores the need for more nuanced approaches based on basic biology. As Mendonça states:
By identifying the specific neural circuits involved, we hope to dispel the fog surrounding the heterogeneity of Parkinson's symptoms and contribute to more precise interventions that can improve the quality of life of people affected by this disease.
A perspective that opens the doors to a future in which Parkinson's therapy will be increasingly personalized and targeted, thanks to neuroscience and precision medicine.
- The caudate nucleus is a C-shaped structure found on both sides of our brain, which plays an essential role in controlling movement, learning, and memory. ↩︎
- The putamen is a brain structure that is part of the basal ganglia. It plays a key role in controlling voluntary movements and motor coordination. It works with the caudate nucleus to help regulate and refine movements, and is also involved in aspects of learning and emotion. ↩︎
