MJFF, Parkinson’s UK fund sleep-based research in Parkinson’s disease
Studies will test whether restorative sleep can improve brain waste clearance
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- New research is exploring whether enhancing restorative sleep may help slow Parkinson’s disease progression.
- REM sleep behavior disorder can occur years before Parkinson’s motor symptoms and is considered an early indicator of the disease.
- Preclinical studies are testing compounds designed to increase slow-wave activity, improve brain waste clearance, and reduce toxic protein buildup.
AstronauTx has received $1.2 million in research funding from The Michael J. Fox Foundation for Parkinson’s Research (MJFF) and Parkinson’s UK to explore whether improving restorative sleep could help slow the progression of Parkinson’s disease.
The MJFF-funded project will investigate whether novel compounds developed by AstronauTx can enhance restorative sleep and reduce the accumulation of toxic protein aggregates linked to Parkinson’s. One of AstronauTx’s programs, ATX0926, is designed to increase slow-wave activity, the slow electrical brain-wave activity that is highest during deep, or slow-wave, sleep, with the aim of supporting the brain’s clearance of neurotoxic proteins.
In parallel, a study led by Ian Harrison at University College London and supported by AstronauTx will further explore whether increasing slow-wave sleep can enhance the brain’s natural waste-clearance process, known as glymphatic flow. This process is more active during deep sleep.
“Restorative sleep mechanisms are an emerging area of interest for therapeutic development in Parkinson’s disease, with the potential to offer new opportunities to intervene earlier in the disease process,” Shalini Padmanabhan, PhD, senior vice president and head of translational research at MJFF, said in a press release.
Funding aims to advance sleep-based approach toward clinical testing
“The studies supported through this award will generate important preclinical evidence to evaluate this therapeutic approach and help determine its potential to advance toward clinical development,” Padmanabhan added.
Parkinson’s is caused by the progressive dysfunction and death of nerve cells that produce dopamine, a signaling molecule involved in controlling movement. A hallmark of Parkinson’s is the accumulation of misfolded alpha-synuclein protein into toxic clumps inside nerve cells, which are believed to contribute to nerve-cell damage.
Sleep problems are common in Parkinson’s, including REM sleep behavior disorder (RBD), a condition in which people act out their dreams. RBD can occur years before the motor symptoms that often lead to a Parkinson’s diagnosis and is considered an early indicator of the disease.
Deep sleep, also known as slow-wave sleep, is the deepest stage of sleep. During this stage, the brain produces slow electrical waves known as slow-wave activity. Deep sleep is thought to support physical recovery and important brain functions, including removing waste products from the brain.
During slow-wave sleep, glymphatic flow — the movement of fluid that helps clear waste from the brain — increases. ATX0926 is designed to increase slow-wave activity with the aim of supporting this waste-clearance process and the clearance of neurotoxic proteins.
The company noted that preclinical work using a compound that acts through the same mechanism as ATX0926 increased slow-wave activity and glymphatic flow and reduced neurotoxic proteins.
Studies examine whether restorative sleep can reduce toxic proteins
The MJFF-funded project, titled “Ligand-Gated Ion Channel Modulation as a Disease-Modifying Treatment for Prodromal Synucleinopathies,” aims to generate preclinical evidence on whether enhancing restorative sleep with compounds developed by AstronauTx can reduce the accumulation of pathological proteins linked to Parkinson’s. The findings may support development of one of the company’s compounds as a potential disease-modifying treatment for the early, or prodromal, stage of Parkinson’s.
The award was made through MJFF’s Parkinson’s Disease Therapeutics Pipeline Program, which supports preclinical and clinical development of potential disease-modifying treatments.
The complementary Parkinson’s UK project, “Measuring the Effects of Increasing Slow-Wave Sleep Using a Novel Mechanism on Glymphatic Transport of Alpha-Synuclein in a Parkinson’s Disease Mouse Model,” will use a mouse model of Parkinson’s to test whether a sleep-enhancing compound that increases slow-wave activity and glymphatic flow can help remove alpha-synuclein from the brain.
“We are grateful for the support from The Michael J. Fox Foundation and Parkinson’s UK as we investigate the relationship between restorative sleep mechanisms and Parkinson’s disease and evaluate the therapeutic potential of these approaches,” said Jane Rhodes, PhD, AstronauTx’s CEO.
“By targeting the mechanisms that regulate restorative sleep, we aim to unlock a completely new approach to treating Parkinson’s disease and other neurological diseases at their earliest stages, and we believe this grant-funded work has the potential to directly support the development of new disease-modifying approaches for patients,” Rhodes added.
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