DMRF-Funded Investigators Evaluate AZD1446 as Possible Dystonia Drug

DMRF and Cure Dystonia Now jointly supported a research investigation to explore whether a drug called AZD1446 could potentially provide relief for dystonia patients with fewer side effects than existing medications. Although AZD1446 did not demonstrate therapeutic effects in animal and cell models of DYT1 dystonia, the investigation produced important findings.

Experiments verified that dystonia is associated with abnormal neuron signaling in the striatum, part of the basal ganglia deep in the brain. This abnormal activity causes an imbalance of two neurotransmitters critical for muscle control: dopamine and acetylcholine.

AZD1446 belongs to a class of drugs called nicotinic agonists. These drugs mimic the action of acetylcholine in the brain. While the data indicate that AZD1446 is not a particularly promising candidate for development as a treatment for DYT1 dystonia, nicotinic agents do appear to have potential. The study suggests that nicotinic agents should continue to be studied to help better understand dystonia and identify new therapies.

DYT1 dystonia typically begins around age 10 years with the twisting of a foot or arm. Symptoms tend to progress to involve additional limbs and the torso. The symptoms tend to be less severe the later in life they start and if they start in a hand or arm. About 30% of individuals who have the DYT1 genetic mutation will develop dystonia. If a person does not manifest symptoms before the age of 28 years, they will usually remain symptom free for life—even if they have the DYT1 mutation.

The investigation was led by Antonio Pisani, MD, PhD, University of Rome Tor Vergata (Italy) and David Standaert, MD, PhD, University of Alabama Birmingham.

Zimmerman, CN, Eskow Jaunarajs KL, Meringolo M, et al. Evaluation of AZD1446 as a Therapeutic in DYT1 Dystonia. Front. Syst. Neurosci., 13 June 2017.


Article republished with permission from DMRF Dystonia Dialogue, Winter 2017. Volume 40, No 3.


Last update: Oct 2022