Our other areas of Research
Caffein (David Blum)
Caffeine is the most widely consumed psychoactive substance in the world. It is well established that it promotes attentional processes, arousal, information processing and therefore has a significant impact on cognitive performance in humans and animals. The main targets of caffeine are receptors called adenosinergic receptors. The effects of caffeine are particularly linked to its ability to block one of these receptors called the A2A adenosinergic receptor.
Recent work also suggests an effect of caffeine on memory processes, and long-term memory in particular, independent of its attentional effects. This observation is linked to various epidemiological studies proposing that habitual caffeine consumption reduces cognitive decline during aging.
Other prospective studies also emphasize the inverse relationship between caffeine consumption and the risk of developing Alzheimer's disease. The protective effects of caffeine would be optimal for doses corresponding to 3 to 4 cups per day.
Finally, our experimental studies on animal models of Alzheimer's disease reproducing the lesions and associated memory disorders demonstrate a beneficial effect of caffeine at comparable doses. The conversation, 23 Juillet 2018)
All of these observations suggest that the use of caffeine or caffeine-derived molecules could be a therapeutic option in patients with Alzheimer's disease. We have set up CAFCA, a multicenter, double-blind, placebo-controlled phase 3 therapeutic trial evaluating the effect of a 30-week caffeine treatment on cognition in early to moderate Alzheimer's disease. https://www.cafca-alzheimer.fr/
Retinal dystrophies and neurodegenerative diseases (Claire-Marie Dhaenens)
MFSD8 gene variants are associated with isolated macular dystrophies (macular damage with reduced visual acuity) but also with syndromic forms: ceroid lipofuscinoses (a group of progressive neurodegenerative genetic diseases clinically characterized by intellectual deficit, epilepsy, and vision loss with retinal degeneration).
Our aim is to study the impact of different MFSD8 genotypes on the CLN7 protein itself and on global gene and protein expression.
This project will allow us to research the markers and mechanisms responsible for the phenotypic continuum linked to mutations in the MFSD8 gene.
RFC1 and Parkinsonian syndromes (Vincent Huin)
Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a neurodegenerative disease characterized by sensory neuronopathy, cerebellar ataxia, and vestibular ataxia. CANVAS is caused by biallelic mutations in intron 2 of the RFC1 gene. The RFC1 gene encodes a ubiquitous protein involved in DNA replication and repair. The phenotype of patients includes chronic cough, dysautonomia, and cognitive impairment.
Our team recently reported cases of parkinsonism in 10% of CANVAS patients. Similarities have also been noted between CANVAS and the clinical impairments observed in multiple system atrophy with the association of cerebellar dysfunction, dysautonomia, cognitive impairment, and parkinsonism. Other studies in small cohorts of Parkinson's disease (PD) patients have reported 1–2% of early-onset PD patients with biallelic RFC1 mutations.
These parkinsonian syndromes are characterized by the abnormal accumulation of α-synuclein aggregates in the brain of patients, classified as synucleinopathies. These observations and preliminary data raise the question of a possible association between RFC1 mutations and the occurrence of synucleinopathies.