Nav: Home

Antihistamines and similar drugs could slow down Huntington's disease

June 09, 2020

Scientists have described a potential new therapeutic strategy for slowing down early-stage Huntington's disease in a new study published today in eLife.

The research in mice indicates that targeting the histamine H3 receptor (H3R) - a well-established drug target for other conditions such as hay fever - could help to prevent imbalances in dopamine signalling that lead to brain-cell death and deficits in movement and memory.

"It was already well known that dopamine signalling goes away in Huntington's disease, but we and other research teams have shown more recently that dopamine receptors and histamine receptors are found together and control signalling in the brain," explains lead author David Moreno-Delgado, who was a Postdoctoral Research Scientist at the University of Barcelona, Spain, at the time the research was carried out, and is now Biology Team Leader at NovAliX, Belgium. "Because dopamine receptors are found in many normal cells throughout the central nervous system, we proposed that targeting dopamine signalling through the histamine receptor might be a more effective strategy to slow the progression of Huntington's disease."

The team looked at whether these protein partners are found together in mice with Huntington's disease and could potentially be targets for treatment. They found that at two- and four-months-old, both healthy mice and those with asymptomatic Huntington's disease have the dopamine D1 receptor (D1R)-H3R complex. But when the team looked at older mice aged six- and eight-months-old, the mice with Huntington's disease (now symptomatic) had completely lost the D1R-H3R complexes. The individual receptors were still present, but at the most advanced stage of the disease, these proteins were no longer acting together as partners.

To confirm the role of the D1R-H3R complex, the team tested the effects of an antihistamine drug called thioperamide on movement, learning and memory in mice with Huntington's disease. Mice treated with thioperamide were only as likely to fall as healthy mice of the same age, while those treated with saline were unable to maintain their balance. Moreover, in a test of memory, the mice treated with saline showed no preference for familiar objects, whereas those treated with thioperamide had no such memory deficits.

The team next explored whether these results were due to the treatment preserving the D1R-H3R complexes. Studies of tissues from treated and untreated mice showed that only the treated animals still had H3R/D1R complexes at six and eight months of age. Moreover, when they treated mice with Huntington's disease that had already reached seven months of age (when these protein partners are no longer found together), thioperamide had no effect on movement, learning or memory deficits. This confirms that the protective effects of thioperamide occurs through the D1R-H3R complexes and that these need to be present for the drug to work.

Finally, the team looked at human brain tissue samples for the presence of D1R-H3R complexes. They found that, in healthy individuals and people with early-stage Huntington's disease, the D1R-H3R complexes were present. By contrast, in people with more advanced disease, the D1R-H3R complexes were almost absent.

"The imbalance of dopamine signalling in disease progression represents a potential 'point of no return' for Huntington's disease patients as it can eventually lead to nerve-cell dysfunction and death," explains senior author Peter McCormick, Senior Lecturer at Queen Mary University of London, UK. "In this study we show that D1R/H3R complexes are found within the brain at early- but not late-disease stages and that targeting these complexes could potentially slow the progression of early-stage disease.

"In addition, our data help explain previous studies attempting to target H3R by showing the dependency on D1R/H3R complexes for these drugs to work. This is important as there are multiple H3R compounds either in the clinic or that have been through phase two and three trials that could be opportunities for drug repurposing."
-end-
Reference

The paper 'Modulation of dopamine D1 receptors via histamine H3 receptors is a novel therapeutic target for Huntington's disease' can be freely accessed online at https://doi.org/10.7554/eLife.51093. Contents, including text, figures and data, are free to reuse under a CC BY 4.0 license.

Media contact

Emily Packer, Senior Press Officer
eLife
e.packer@elifesciences.org
01223 855373

About eLife

eLife is a non-profit organisation created by funders and led by researchers. Our mission is to accelerate discovery by operating a platform for research communication that encourages and recognises the most responsible behaviours. We work across three major areas: publishing, technology and research culture. We aim to publish work of the highest standards and importance in all areas of biology and medicine, including Neuroscience, while exploring creative new ways to improve how research is assessed and published. We also invest in open-source technology innovation to modernise the infrastructure for science publishing and improve online tools for sharing, using and interacting with new results. eLife receives financial support and strategic guidance from the Howard Hughes Medical Institute, the Knut and Alice Wallenberg Foundation, the Max Planck Society and Wellcome. Learn more at https://elifesciences.org/about.

To read the latest Neuroscience research published in eLife, visit https://elifesciences.org/subjects/neuroscience.

eLife

Related Memory Articles:

Memory of the Venus flytrap
In a study to be published in Nature Plants, a graduate student Mr.
Memory protein
When UC Santa Barbara materials scientist Omar Saleh and graduate student Ian Morgan sought to understand the mechanical behaviors of disordered proteins in the lab, they expected that after being stretched, one particular model protein would snap back instantaneously, like a rubber band.
Previously claimed memory boosting font 'Sans Forgetica' does not actually boost memory
It was previously claimed that the font Sans Forgetica could enhance people's memory for information, however researchers from the University of Warwick and the University of Waikato, New Zealand, have found after carrying out numerous experiments that the font does not enhance memory.
Memory boost with just one look
HRL Laboratories, LLC, researchers have published results showing that targeted transcranial electrical stimulation during slow-wave sleep can improve metamemories of specific episodes by 20% after only one viewing of the episode, compared to controls.
VR is not suited to visual memory?!
Toyohashi university of technology researcher and a research team at Tokyo Denki University have found that virtual reality (VR) may interfere with visual memory.
The genetic signature of memory
Despite their importance in memory, the human cortex and subcortex display a distinct collection of 'gene signatures.' The work recently published in eNeuro increases our understanding of how the brain creates memories and identifies potential genes for further investigation.
How long does memory last? For shape memory alloys, the longer the better
Scientists captured live action details of the phase transitions of shape memory alloys, giving them a better idea how to improve their properties for applications.
A NEAT discovery about memory
UAB researchers say over expression of NEAT1, an noncoding RNA, appears to diminish the ability of older brains to form memories.
Molecular memory can be used to increase the memory capacity of hard disks
Researchers at the University of Jyväskylä have taken part in an international British-Finnish-Chinese collaboration where the first molecule capable of remembering the direction of a magnetic above liquid nitrogen temperatures has been prepared and characterized.
Memory transferred between snails
Memories can be transferred between organisms by extracting ribonucleic acid (RNA) from a trained animal and injecting it into an untrained animal, as demonstrated in a study of sea snails published in eNeuro.
More Memory News and Memory Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: The Power Of Spaces
How do spaces shape the human experience? In what ways do our rooms, homes, and buildings give us meaning and purpose? This hour, TED speakers explore the power of the spaces we make and inhabit. Guests include architect Michael Murphy, musician David Byrne, artist Es Devlin, and architect Siamak Hariri.
Now Playing: Science for the People

#576 Science Communication in Creative Places
When you think of science communication, you might think of TED talks or museum talks or video talks, or... people giving lectures. It's a lot of people talking. But there's more to sci comm than that. This week host Bethany Brookshire talks to three people who have looked at science communication in places you might not expect it. We'll speak with Mauna Dasari, a graduate student at Notre Dame, about making mammals into a March Madness match. We'll talk with Sarah Garner, director of the Pathologists Assistant Program at Tulane University School of Medicine, who takes pathology instruction out of...
Now Playing: Radiolab

What If?
There's plenty of speculation about what Donald Trump might do in the wake of the election. Would he dispute the results if he loses? Would he simply refuse to leave office, or even try to use the military to maintain control? Last summer, Rosa Brooks got together a team of experts and political operatives from both sides of the aisle to ask a slightly different question. Rather than arguing about whether he'd do those things, they dug into what exactly would happen if he did. Part war game part choose your own adventure, Rosa's Transition Integrity Project doesn't give us any predictions, and it isn't a referendum on Trump. Instead, it's a deeply illuminating stress test on our laws, our institutions, and on the commitment to democracy written into the constitution. This episode was reported by Bethel Habte, with help from Tracie Hunte, and produced by Bethel Habte. Jeremy Bloom provided original music. Support Radiolab by becoming a member today at Radiolab.org/donate.     You can read The Transition Integrity Project's report here.