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Save the Neurons: Fighting the Effects of Parkinsons

Photo credit goes to the The Michael J. Fox Foundation for Parkinson's Research

Photo credit goes to: the The Michael J. Fox Foundation for Parkinson’s Research

Possibly one of the most famous cases of parkinson’s is Michael J. Fox. More than just the “shakes” parkinson’s can cause a whole host of other problems mentally and physically [things like lack of sleep, smell, and mood]. But now an experimental anti-inflammatory drug ,funded by the foundation with is namesake has been shown to protect vulnerable neurons and reduce motor deficits, at least in a rat model of Parkinson’s disease.

The findings show that the drug, called XPro1595, can reach the brain at sufficient levels [since most drugs have problems crossing the blood brain barrier] and have beneficial effects when administered by subcutaneous injection, just underneath the skin as opposed to into the muscle. This was a big step toward clinical trials because previous studies of XPro1595 [in animals] tested more invasive modes of delivery, such as direct injection into the brain [which is why this is a big deal].

“This is an important step forward for anti-inflammatory therapies for Parkinson’s disease,” says Malu Tansey, PhD, associate professor of physiology at Emory University School of Medicine. “Our results provide a compelling rationale for moving toward a clinical trial in early Parkinson’s disease patients.”

The new research on subcutaneous administration of XPro1595 like I mentioned earlier, was funded by the Michael J. Fox Foundation for Parkinson’s Research [MJFF since we love to shorten things in science]. XPro1595 is licensed by FPRT Bio, and thanks to this new research is seeking funding for a clinical trial to test its efficacy, albeit only in the early stages of Parkinson’s disease.

“We are proud to have supported this work and glad to see positive pre-clinical results,” said Marco Baptista, PhD, MJFF associate director of research programs. “A therapy that could slow Parkinson’s progression would be a game changer for the millions living with this disease, and this study is a step in that direction.”

In the scientific community evidence has been piling up that inflammation is an important mechanism driving the progression of Parkinson’s disease. XPro1595 [because the guy who names the drugs was off that day] targets something called tumor necrosis factor [TNF] — which is a critical inflammatory signaling molecule– and is specific to the soluble form of TNF. This specificity helps avoid compromising immunity to infections, a previous stumbling block, because it is a known side effect of existing anti-TNF drugs that are typically used to treat disorders such as rheumatoid arthritis.

“Inflammation is probably not the initiating event in Parkinson’s disease, but it is important for the neurodegeneration that follows,” Tansey says. “That’s why we believe that an anti-inflammatory agent, such as one that counteracts soluble TNF, could substantially slow the progression of the disease.”

About the experiment, the team used a model of Parkinson’s disease in rats, to accomplish this neurotoxin 6-hydroxydopamine [6-OHDA] is injected into only one side of the brain. This reproduces some of the aspects of Parkinson’s disease: the neurons that produce dopamine in the injected side of the brain die, this leads to impaired movement on the opposite side of the body.

When the XPro1595 is given to the animals [3 days after 6-OHDA injection] only 15 percent of the dopamine-producing neurons were lost five weeks later. Incredible when you compare that number to the control rats, in which 55 percent of the same neurons were lost. By reducing dopamine neuron loss with XPro1595, the researchers were also able to reduce motor impairment. In fact, the degree of dopamine cell loss was highly correlated both with the degree of motor impairment and the bodies immune cell activation.

A caveat to this, unfortunately when XPro1595 is given two weeks after injection, 44 percent of the vulnerable neurons are still lost, this means that there is probably a limited window of opportunity to intervene.

“Recent clinical studies indicates there is a four or five year window between diagnosis of Parkinson’s disease and the time when the maximum number of vulnerable neurons are lost,” Dr. Tansey says. “If this is true, and if inflammation is playing a key role during this window, then we might be able to slow or halt the progression of Parkinson’s with a treatment like XPro1595.”

Just one more hope for the future to save people from neurological diseases like this one. Call me greedy, but I think it would be awesome to never see people have to just live with it. With any luck this will go to clinical trials soon and if it goes smoothly, well you can guess.

Want the full study? Yay, you can find that —here!!

Sources
Barnum CJ, Chen X, Chung J, Chang J, Williams M, Grigoryan N, Tesi RJ, & Tansey MG (2014). Peripheral Administration of the Selective Inhibitor of Soluble Tumor Necrosis Factor (TNF) XPro1595 Attenuates Nigral Cell Loss and Glial Activation in 6-OHDA Hemiparkinsonian Rats. Journal of Parkinson’s disease PMID: 25061061

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