Nav: Home

Antibiotic doxycycline may offer hope for treatment of Parkinson's disease

May 03, 2017

A study published in February in the journal Scientific Reports suggests that doxycycline, an antibiotic used for over half a century against bacterial infections, can be prescribed at lower doses for the treatment of Parkinson's disease.

According to the authors, the substance reduces the toxicity of α-synuclein, a protein that, under certain conditions, forms abnormal accumulations of aggregates in central nervous system cells, which are damaged as a result. The death of dopaminergic neurons (which produce the neurotransmitter dopamine) is the main event relating to the development of such symptoms as tremor, slow voluntary movements and stiffness, among others. There are currently no drugs capable of halting the progress of this degenerative process.

Three Brazilian scientists participated in the study, which was supported by FAPESP: Elaine Del-Bel, affiliated with the University of São Paulo's Ribeirão Preto Dental School (FORP-USP), and Leandro R. S. Barbosa and Rosangela Itri, at the same university's Physics Institute (IF-USP) in the city of São Paulo.

"We have exciting data from experiments with mice and great expectations that the neuroprotective effect will also be observed in human patients," Del-Bel told. "This treatment could stop Parkinson's from progressing, and we therefore plan to start a clinical trial shortly."

The discovery happened fortuitously some five years ago when Marcio Lazzarini, a former student of Del-Bel, was pursuing postdoctoral studies at the Max Planck Institute of Experimental Medicine in Germany.

While looking for possible alternative treatments for Parkinson's in experiments with mice, the group used a well-known model for inducing a condition similar to the human disease. The model consists of administering 6-hydroxydopamine (6-OHDA), a neurotoxin that causes the death of dopaminergic neurons.

"To our surprise, only two of the 40 mice given 6-OHDA developed symptoms of Parkinsonism, while the rest remained healthy," Del-Bel said. "A lab technician realized the mice had mistakenly been fed chow containing doxycycline, so we decided to investigate the hypothesis that it might have protected the neurons."

The group repeated the experiment, adding a second group of animals that were given doxycycline in low doses by peritoneal injection instead of receiving it in their feed. Both cases were successful.

Understanding the mechanisms behind the neuroprotective effect of doxycycline has been the focus for the most recent studies, conducted in collaboration with the group led by Rosana Chehin, a researcher at the University of Tucumán in Argentina, as well as Rita Raisman-Vozari and Julia Sepulveda-Diaz, researchers at the Brain & Bone Marrow Institute (ICM) in Paris, France.

In these new trials, which involved structural and spectroscopic characterization methods, the focus was the protein α-synuclein, considered one of the leading causes of dopaminergic neuron death.

"α-Synuclein is a small unstructured protein that, in the presence of the cellular membrane, aggregates to form fibrils with multiple regularly ordered layers of beta- sheets along the axis. We call these amyloid fibrils. It's been proven that large amyloid fibrils of this protein aren't toxic to cells; what damages cells is the so-called oligomeric stage formed by small amounts of aggregated α-synuclein. These oligomers can damage neuron membranes," Itri said.

The researchers synthesized small oligomers of α-synuclein and conducted in vitro trials to find out whether doxycycline interfered in the process of aggregation and fibril formation.

With a combination of three different techniques - nuclear magnetic resonance, X-ray scattering and infrared spectroscopy - they were able to observe two distinct situations. In medium without doxycycline, α-synuclein aggregated and began forming amyloid fibrils. In medium containing the antibiotic, α-synuclein formed another type of aggregate with a different shape and size. "In the tests with cultured cells and model membranes, we observed that they caused no damage to the cell membrane," Itri said.

The tests in culture were performed in immortalized human neuroblastoma cells. Using transmission electron microscopy, the group observed that the presence of doxycycline in the culture medium reduced α-synuclein aggregation by more than 80%. "As a result, cell viability increased by more than 80%," Del-Bel said.

Del-Bel has more deeply investigated the effects of treatment with doxycycline on mice. "We haven't published any data yet, but I can say right away that doxycycline improves the symptoms of the disease in the animal model," Del-Bel added. "Preliminary results suggest that besides its anti-inflammatory action via a reduction in the release of some cytokines, doxycycline also alters the expression of key genes for the development of Parkinson's."

According to Del-Bel, evidence in the scientific literature shows that α-synuclein aggregates on and causes damage to not just neurons but also astrocytes and other glial cells. Besides Parkinson's, therefore, the process is associated with the development of other neurodegenerative diseases, such as Lewy body dementia (LBD), the second most common neurodegenerative disease after Alzheimer's. Future studies will investigate whether doxycycline can also have a beneficial effect in these other situations.

Fundação de Amparo à Pesquisa do Estado de São Paulo

Related Antibiotic Articles:

Pollution linked to antibiotic resistance
Antibiotic resistance is an increasing health problem, but new research suggests it is not only caused by the overuse of antibiotics.
Antibiotic resistance and the need for personalized treatments
Scientists have discovered that the microbiota of each individual determines the maintenance of antibiotic resistant bacteria in the gut: whereas in some individuals resistant bacteria are quickly eliminated, in others they are not.
Artificial intelligence yields new antibiotic
Using a machine-learning algorithm, MIT researchers have identified a powerful new antibiotic compound.
From cancer medication to antibiotic
Antibiotic-resistant bacteria are increasingly the source of deadly infections. A team of scientists from the Technical University of Munich (TUM) and the Helmholtz Center for Infection Research (HZI) in Braunschweig have now modified an approved cancer drug to develop an active agent against multidrug-resistant pathogens.
Up to two-fifths of antibiotic prescriptions in the US could be inappropriate
As much as two fifths (43%) of antibiotic prescriptions in the United States could be inappropriate, warn researchers in a study published by The BMJ today.
New understanding of antibiotic synthesis
Researchers at McGill University's Faculty of Medicine have made important strides in understanding the functioning of enzymes that play an integral role in the production of antibiotics and other therapeutics.
Cause of antibiotic resistance identified
Bacteria can change form in human body, hiding the cell wall inside themselves to avoid detection.
Cannabidiol is a powerful new antibiotic
New research has found that Cannnabidiol is active against Gram-positive bacteria, including those responsible for many serious infections (such as Staphyloccocus aureus and Streptococcus pneumoniae), with potency similar to that of established antibiotics such as vancomycin or daptomycin.
New approaches cut inappropriate antibiotic use by over 30%
A UC Davis study of nine emergency departments and urgent care centers in California and Colorado found educating physicians and patients about safe antibiotic use can cut overuse by one-third.
How certain antibiotic combinations could defeat 'superbugs'
In hospitalized patients with bacterial infections, heteroresistance is more widespread than previously appreciated.
More Antibiotic News and Antibiotic 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     You can read The Transition Integrity Project's report here.