ADCY5-related Dyskinesia Clinical Trial
Official title:
Study of Caffeine Efficacy in ADCY5-related Dyskinesia - a Retrospective Study
Heterozygous mutations in ADCY5 induce hyperactivity of striatal adenylate cyclase type 5
(AC5), manifesting as early-onset hyperkinetic movement disorders. Numerous treatments have
been tried without much efficacy thus far. Two patients from the same family reported
efficacy of caffeine on paroxysmal episodes, both to prevent episodes and to reduce their
duration (efficacy estimated to be around 80%), which was specific to caffeine as it was
reproduced with caffeine citrate capsules. Interestingly, there is a rationale underlying
this observation. Indeed, caffeine is an antagonist of adenosine A2A receptors (A2AR), which
activate AC5 and are localized preferentially in striatal neurons that express dopamine
receptors D2 .Caffeine therefore likely induces AC5 inhibition, and thus clinical improvement
in patients with hyperactivity of this protein. This observation has been recently published
in2019.
The investigators will collect preliminary data by interviewing our neurologist and
neuropediatric colleagues, in France and abroad since it is a rare disease, on the effect of
caffeine on motor symptoms and global clinical status in their ADCY5 patients.
Heterozygous mutations in ADCY5 induce hyperactivity of striatal adenylate cyclase type 5
(AC5) manifesting as early-onset hyperkinetic movement disorders. The phenotype combines
chorea, dystonia and/or myoclonus with frequent facial involvement, axial hypotonia,
fluctuations and/or episodes of paroxysmal dyskinesia which can be nocturnal and/or painful,
generally without intellectual deficiency, epilepsy or cerebellar syndrome . It is a very
rare disease, affecting around twenty patients in France.
Scientific context of the research:
Numerous treatments have been tried without much efficacy thus far.
Scientific justification for the study:
Two patients from the same family reported efficacy of caffeine on paroxysmal episodes, both
to prevent episodes and to reduce their duration (efficacy estimated to be around 80%), which
was specific to caffeine as it was reproduced with caffeine citrate capsules. Interestingly
there is a rationale underlying this situation. Indeed, caffeine is an antagonist of
adenosine A2A receptors (A2AR), which activate AC5 and are localized preferentially in
striatal neurons that express dopamine receptors D2. Caffeine therefore likely induces
inhibition of AC5, and thus clinical improvement in patients with hyperactivity of this
protein. This observation has been recently published in 2019 HYPOTHESIS Our hypothesis is
that most patients with ADCY5-related dyskinesia respond well to caffeine.
This study is a multicentric retrospective study, which will be conducted in neurology and
neuropediatric departments across the world.
Participants will be recruited by their own physician. This research will take place over 18
months in total: 12 month to collect all patients' data and 6 months to analyse data.
The number of participants will be between 5 and 20, depending on colleagues replies.
This research will take place over 18 months in total: 12 month to collect all patients' data
and 6 months to analyse data.
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| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Recruiting |
NCT05136495 -
Assessment of ADCY5-related Movement Disorders With Motion SENSors
|
N/A |