NWPF

News ArchivesRead News

Anti-inflammatory Drug Can Prevent Neuron Loss in Parkinson's Model

Friday July 25, 2014

Science Codex - An experimental anti-inflammatory drug can protect vulnerable neurons and reduce motor deficits in a rat model of Parkinson's disease, researchers at Emory University School of Medicine have shown.

The results were published in the Journal of Parkinson's Disease.

The findings demonstrate that the drug, called XPro1595, can reach the brain at sufficient levels and have beneficial effects when administered by subcutaneous injection, like an insulin shot. Previous studies of XPro1595 in animals tested more invasive modes of delivery, such as direct injection into the brain.

"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 was funded by the Michael J. Fox Foundation for Parkinson's Research (MJFF). XPro1595 is licensed by FPRT Bio, and is seeking funding for a clinical trial to test its efficacy 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 addition, Tansey and Yoland Smith, PhD, from Yerkes National Primate Research Center, were awarded a grant this week from the Parkinson's Disease Foundation to test XPro1595 in a non-human primate model of Parkinson's.

Evidence has been piling up that inflammation is an important mechanism driving the progression of Parkinson's disease. XPro1595 targets tumor necrosis factor (TNF), a critical inflammatory signaling molecule, and is specific to the soluble form of TNF. This specificity would avoid compromising immunity to infections, a known side effect of existing anti-TNF drugs 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."

Postdoctoral fellow Christopher Barnum, PhD and colleagues used a model of Parkinson's disease in rats in which the neurotoxin 6-hydroxydopamine (6-OHDA) is injected into only one side of the brain. This reproduces some aspects of Parkinson's disease: neurons that produce dopamine in the injected side of the brain die, leading to impaired movement on the opposite side of the body.

When XPro1595 is given to the animals 3 days after 6-OHDA injection, just 15 percent of the dopamine-producing neurons were lost five weeks later. That compares to controls 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 immune cell activation.

When XPro1595 is given two weeks after injection, 44 percent of the vulnerable neurons are still lost, suggesting that there is 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."

(25 July 2014). Science Codex. Anti-inflammatory Drug Can Prevent Neuron Loss in Parkinson's Model. http://www.sciencecodex.com/antiinflammatory_drug_can_prevent_neuron_loss_in_parkinsons_model-138343

Recent News

Oct 17 - Scientists Identify Structure of PINK1, Key Parkinson’s-protective Protein
Oct 17 - Diabetes drug cuts Parkinson's risk by 28 percent, study finds
Oct 10 - Advances in Brain Pacemaker Reduces Tremors, Helps Parkinson's Sufferers Live a More Normal Life
Oct 10 - Medical History Could Help Predict Parkinson's Disease Risk Long Before Diagnosis
Oct 3 - Changes in Olfactory Bulb Explain Loss of Smell in Early Stages of Parkinson’s Disease, Study Finds
Oct 3 - Sleep Disturbances May Worsen Motor Symptoms in Parkinson’s Disease, Study Suggests
Sep 12 - Australian Researchers Develop New Diagnostic Tool to Spot Early Signs of Parkinson’s
Sep 11 - GeneFo Webinar to Focus on Using Humor to Manage Parkinson’s Disease
Sep 6 - Parkinson’s and the ‘D’ word
Sep 6 - Compounds in Asthma Drugs Might Be Used as Parkinson’s Treatment
Sep 5 - AstraZeneca Joins Takeda, Berg to Advance Development of Parkinson’s Disease Therapies
Sep 1 - Stem Cell Transplant Trial in Parkinson’s Patients Planned After Test in Japan Succeeds in Monkeys
Sep 1 - Titan to Start Phase 1/2 Study of Subdermal Implant to Deliver Requip to Parkinson’s Patients
Aug 30 - FDA Refuses Acorda’s Inbrija New Drug Application Due to Manufacturing Questions
Aug 23 - Support Groups: Are They for You?
Aug 22 - Internet Visits with Parkinson’s Specialist Can Be as Effective as In-person Visits, Trial Finds
Aug 21 - Cavion’s New CMO to Lead Cav3 Platform Development for Neurological Diseases
Aug 15 - Singing Helps Early-stage Parkinson’s Patients Retain Speech, Respiratory Control, Studies Show
Aug 14 - 16 Tips to Increase Your Mobility Confidence While Living With Parkinson’s Disease
Aug 10 - Boxers are fighting back against Parkinson’s