Our team specializes in the use of functional imaging to advance towards two objectives: - the identification of diagnostic markers or markers of the progression of neurodegenerative diseases (=biomarkers)
- the exploitation of these markers to study the effects of innovative treatments, such as biotherapies in particular, on these diseases.
This approach is made possible by the use of high-resolution imaging tools, the availability of radiotracers (cyclotron) at the SHFJ and access to cohorts of patients through collaboration with the teams at the Salpêtrière and Henri Mondor Hospitals.
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Identification of Biomarkers |
In Parkinson’s disease, markers of dopaminergic neuron loss, the key feature of this condition, have long been used to assess disease progression. We have also studied other phenomena, such as abnormalities of nicotinic receptors, of this disease. We are currently investigating whether inflammatory processes contribute to neuron cell death in this disease, using a tracer likely to provide evidence of such processes in the zones in which neuron death occurs. We are also exploring the phenotype of subjects carrying a mutation (LRRK2) that may cause Parkinson’s disease, to determine the duration of the preclinical phase of the disease and to identify markers of this phase. |
(Douaud et al., 2006)
For Huntington’s disease, we use the classical markers of progression of this disease: morphological abnormalities on MRI (e.g. striatal atrophy, figure 1) or decreases in metabolism and in the density of striatal D2 receptors.
Evaluation of innovative treatments
We have been involved in analyses of the effect of fetal neuron grafts in a pilot trial on patients with Huntington’s disease (Bachoud-Lévi et al., Lancet 2000, Lancet Neurol 2006, Gaura et al., Brain 2004, figure 2). This work is currently continuing in the framework of a multicenter controlled trial.
In the near future, other treatments, such as gene therapy, will be evaluated with these tools.
Figure 2: Striatal hypermetabolism in a patient with Huntington’s disease after the grafting of fetal neurons
Similar studies have been carried out for Parkinson’s disease: imaging was used to evaluate neuron grafts in the 1990s, and is now used to explore the efficacy of gene therapy in this disease. However, imaging is also used to assess the progression of the disease with a view to identifying drugs that could slow this process (neuroprotective). Finally, functional imaging can also provide descriptions of the mode of action of treatments based on deep brain electric stimulation of the in this disease (Payoux et al., Arch. Neurol., 2004). This technique can also help to explain the adverse effects of deep brain stimulation, particularly those of a psychiatric nature (Mallet et al. PNAS, 2007).
Members of the laboratory associated with these projects
- Sonia Lavisse (researcher)
- Dr Véronique Gaura (neurologist and nuclear medicine doctor at Saint Antoine Hospital)
- Neurologists (placements): Dr Larent Cleret (Henri Mondor Hospital), Dr Claire Thiriez (Henri Mondor Hospital).
Collaborations and funding
- We work with other imaging teams in Lyons (CERMEP), London and Vancouver.
- We work in close collaboration with 1) Frédéric Joliot Hospital at Orsay (SHFJ-CEA) and 2) the neurogenetics and neurology teams of Salpêtrière Hospital and the neurosurgical team at Henri Mondor Hospital.
- We receive funding from public bodies (PHRC), foundations (Fondation de l’Avenir) and patients’ associations (France-Parkinson). Recent publications