- The compound itanapraced was found to reverse damage to brain cells caused by Parkinson’s disease (PD) in cultured neurons and animal models.
- The potential early stage Alzheimer’s drug breaks a vicious cycle caused by the LRRK2 gene mutation, a common gene mutation linked to PD.
- These findings open the possibility of a common drug to treat both PD and Alzheimer’s disease.
Singapore, 19 October 2022 – Researchers from Singapore have identified how a gene mutation causes a vicious cycle resulting in damage to brain cells linked to Parkinson’s disease (PD) and an experimental drug for cognitive impairment can break this cycle and reverse the damage.
LRRK2 is a common gene mutation linked to PD. People who have Asian specific variants of this mutation have a 1.5 to 2-fold increased risk of getting PD. LRRK2 triggers toxic changes in brain cells that are responsible for producing dopamine. Dopamine is a neurotransmitter required for movement – a lack of dopamine results in symptoms of PD such as uncontrollable tremors, slow movement and stiffness.
LRRK2 can damage dopamine-producing neurons in several ways. The team’s studies on cultured neurons and animal models found a self-sustaining molecular loop between LRRK2 and AICD, a portion of the APP gene, which is also an important molecule in Alzheimer’s disease. This loop damages mitochondria (needed to generate energy for cell functions) in dopamine-producing neurons, resulting in neuron cell loss and PD. (See Annex B for details). The researchers also discovered that the potential cognitive impairment drug itanapraced could break this cycle and reverse damage to the dopamine-producing neurons.
Breaking this self-perpetuating cycle not only reduced neuron damage in models with the LRRK2 gene mutation but also in PD models with no genetic cause (idiopathic PD). The team’s findings were published in Science Signaling
“We found that AICD promotes LRRK2 activity and this is highly interesting because it connects AICD and LRRK2 on a common pathway; so drugs targeting the AICD could not only work for AD, but also PD”, said Associate Professor Zeng Li, a Senior Research Scientist and project co-lead, NNI.
Itanapraced has undergone phase II clinical trials for cognitive impairment, so it has already passed the necessary safety tests required for testing in humans.
“This important discovery opens the way to finding a common therapeutic target for both Parkinson disease and Alzheimer’s disease which are the two most common neurodegenerative diseases globally. This novel drug has the potential to improve and preserve the function and quality of life for those afflicted with these diseases,” said Professor Louis Tan, Director, Research and Senior Consultant, Department of Neurology, NNI.
The team’s next steps are to study how reversing damage to dopamine-producing neurons using itanapraced affects PD symptoms in both patients with LRRK2 and idiopathic PD.