In Accidental Discovery, Antibiotic Doxycycline Prevents Nerve Cell Damage in Mice with Parkinson’s

Brazilian researchers discovered by accident that the antibiotic doxycycline prevented nerve cell damage in mice with Parkinson’s disease, a finding that was so exciting that they and colleagues from other countries decided to delve further into the subject.

They have come up with a number of findings indicating doxycycline could be a major Parkinson’s treatment, and they are now looking at whether it can help with other neurodegenerative diseases.

The teams have already identified how doxycycline protects from injury a special kind of nerve cell that is affected in Parkinson’s, called the dopaminergic neuron. The results, “Repurposing doxycycline for synucleinopathies: remodelling of α-synuclein oligomers towards non-toxic parallel beta-sheet structured species,” were published in the journal Scientific Reports.

Brazilian researchers discovered doxycycline’s ability to prevent Parkinson’s symptoms when mice were mistakenly fed chow containing the antibiotic. Thirty-eight of 40 mice that had been programmed to develop Parkinson’s disease for research purposes showed no symptoms after eating doxycycline-laced food.

Teams from Argentina and France collaborated with the Brazilians to confirm the results. To see how doxycycline protects dopaminergic neurons from injury, they studied its effect on a protein called alpha-synuclein that is believed to be a major player in neuron death.

They tested nerve cells cultured in a laboratory. A key finding was that alpha-synuclein, which injures the cell membranes of neurons and kills the cells, does not damage membranes in the presence of doxycycline. In fact, the antibiotic increased the survival of cells grown with artificially produced alpha-synuclein by more than 80%.

Doxycycline may have other beneficial effects in Parkinson’s, Elaine Del Bel, who is with the University of São Paulo’s Ribeirão Preto Dental School, said in a press release.

It appears to protect other kinds of brain cells, called glial cells, from injury, according to additional studies her team is doing with mice. It also appears to affect genes that play a role in the disease and the immune system.

The results prompted the team to plan studies on doxycycline’s effects on other neurological diseases.

“We haven’t published any data yet, but I can say right away that doxycycline improves the symptoms of the disease [Parkinson’s] in the animal model,” Del-Bel said.  “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.

“We have exciting data from experiments with mice and great expectations that the neuroprotective effect will also be observed in human patients,” she added. “This treatment could stop Parkinson’s from progressing, and we therefore plan to start a clinical trial shortly.”

Parkinson’s is a neurodegenerative disorder that causes progressively worsening problems with motor function. Early signs include shaking, rigidity, slowness of movement, and difficulty with walking.