In late-stage Parkinson’s disease, the drug levodopa becomes less effective in treating symptoms because of the inexorable loss of dopamine-releasing neurons. But a new preclinical study shows a gene therapy targeting the small brain region where these neurons reside, the substantia nigra, substantially boosts the benefits of levodopa.
The gene therapy restored the ability of neurons in the substantia nigra to convert levodopa to dopamine. In essence, this allowed levodopa to recreate the environment found in the healthy brain and eliminated the aberrant brain activity responsible for difficulty in moving.
In the same study, scientists also provide an explanation for why dopamine-releasing neurons are lost in the disease. Using advanced genetic tools, the authors show that damage to the powerplants inside dopamine-releasing neurons (mitochondria) is sufficient to trigger a sequence of events that faithfully recapitulates what happens to brain circuits in Parkinson’s disease.
The findings in mice published in Nature, may help identify humans in the earliest stages of Parkinson’s disease, develop therapies to slow disease progression and treat late-stage disease.
The key new findings:
Damage to the power plants in dopamine-releasing neurons is enough to cause Parkinson’s disease. When these power plants (mitochondria) begin to shut down, the ability of neurons to do their jobs in the brain is compromised. Without a sufficient source of energy, neurons eventually wither and die. This finding opens a new path to develop therapies to protect the function of mitochondria.
Contrary to the past 30 years of thinking, the emergence of the motor symptoms of Parkinson’s disease requires the loss of dopamine release in a small region of the brain called the substantia nigra. This discovery also opens the door to new therapies for late-stage Parkinson’s disease patients.
Scientists demonstrated that a gene therapy targeting the substantia nigra effectively boosts the symptomatic benefit of levodopa.
“The development of effective therapies to slow or stop Parkinson’s disease progression requires scientists know what causes it,” said the lead study author. “This is the first time there has been definitive evidence that injury to mitochondria in dopamine-releasing neurons is enough to cause a human-like parkinsonism in a mouse.
“Whether mitochondrial damage was a cause or consequence of the disease has long been debated. Now that this issue is resolved, we can focus our attention on developing therapies to preserve their function and slow the loss of these neurons.”
In addition to providing a clear target for disease-modifying therapies, the study provides a model of Parkinson’s disease before clinical symptoms appear. The slow, progressive loss of dopamine-releasing neurons in the model allowed researchers to see what may be happening in the brain well before movement becomes difficult.
“This new ‘human-like’ model may help us develop tests that would identify people who are on their way to being diagnosed with Parkinson’s disease in five or 10 years,” the lead said. “Doing so would allow us to get them started early on therapies that could alter disease progression.”
https://www.nature.com/articles/s41586-021-04059-0
Disruption of mitochondrial complex I induces progressive parkinsonism
- 1,386 views
- Added
Edited
Latest News
Protein that helps COVID-19…
By newseditor
Posted 26 Jul
Spinal Muscular Atrophy (SM…
By newseditor
Posted 26 Jul
Link between bowel movement…
By newseditor
Posted 26 Jul
Inhibition of IL-11 signall…
By newseditor
Posted 25 Jul
Brain changes linked to obe…
By newseditor
Posted 25 Jul
Other Top Stories
Why are memories attached to emotions so strong?
Read more
A drug reduces stroke damage by preventing potassium release from n…
Read more
Vulnerabilities involved in human tooth decay
Read more
How does the brain fold?
Read more
Regulatory region of human embryonic brain telencephalon dissected!
Read more
Protocols
A systems biology approach…
By newseditor
Posted 24 Jul
quantms: a cloud-based pipe…
By newseditor
Posted 22 Jul
Emerging tools and best pra…
By newseditor
Posted 19 Jul
Directly selecting cell-typ…
By newseditor
Posted 17 Jul
PUFFFIN: an ultra-bright, c…
By newseditor
Posted 16 Jul
Publications
Hepatocyte-intrinsic SMN de…
By newseditor
Posted 26 Jul
Aberrant bowel movement fre…
By newseditor
Posted 26 Jul
A pseudoautosomal glycosyla…
By newseditor
Posted 26 Jul
Microglia protect against a…
By newseditor
Posted 26 Jul
Rigor and reproducibility i…
By newseditor
Posted 26 Jul
Presentations
Myelin plasticity in the ve…
By newseditor
Posted 10 Jun
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar