A clinical trial may soon be initiated for a new treatment for Parkinson’s Disease as a result of work conducted in the laboratory of Malu Tansey, PhD, associate professor of physiology at Emory University School of Medicine. Dr. Tansey’s research team, along with a colleague at FPRT Bio, Inc., an emerging drug development company with ties to the Dallas-Fort Worth region, published findings that show a new molecule known as XPro1595 treats an animal model of Parkinson’s Disease. The article appears in Journal of Parkinson’s Disease.
“Our results provide a compelling rationale for moving toward a clinical trial in early Parkinson’s disease patients,” said Dr. Tansey in a news release.
XPro1595, licensed by FPRT Bio, is a selective inhibitor of soluble tumor necrosis factor (TNF), giving it targeted anti-inflammatory properties without the immune-compromising side effects common to other anti-TNF drugs. Since ongoing neuroinflammation is a hallmark of Parkinson’s Disease, Dr. Tansey’s team was interested in XPro1595’s effects in a rat model of Parkinson’s Disease. The goal of the study was to determine if XPRo1595 could cross the blood brain barrier at a clinically-relevant dose, attenuate neruoinflammation, and halt the death of substantia nigra pars compacta neurons that produce dopamine. “This [study was] an important step forward for anti-inflammatory therapies for Parkinson’s disease,” commented Dr. Tansey.
The animal model used by Dr. Tansey and postdoctoral fellow Christopher Barnum, PhD, involved a rat receiving 6-hydroxydopamine (6-OHDA), a neurotoxin, in one side of its brain. Three days after injecting 6-OHDA, the team injected the rats with XPro1595. As a result, only 15% of dopamine-producing neurons were lost five weeks later, compared to 55% lost by rats not receiving XPro1595 injections. As a direct consequence, the XPro1595 rodents experienced less severe motor impairment, and dopamine cell loss correlated to both the degree of motor impairment and immune cell activation. Evidently, enough XPro1595 crossed the blood brain barrier following injection to have a beneficial effect.
Yet, the window of efficacy for XPro1595 is short. When it was injected two weeks after 6-OHDA injection, 44% of dopamine-producing neurons were lost. “Recent clinical studies indicate 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,” said Dr. Tansey. “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.”
Funding for the study was provided by the Michael J. Fox Foundation for Parkinson’s Research. “We are proud to have supported this work and glad to see positive pre-clinical results,” said Marco Baptista, PhD, associate director of research programs at the Foundation. “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.”
Further work will be funded by the Parkinson’s Disease Foundation. Dr. Tansey, along with Yoland Smith, PhD, from Yerkes National Primate Research Center, which will study XPro1595 in a non-human primate model of Parkinson’s Disease. In vivo tests of this caliber closely precede first-in-human clinical trials.
“Inflammation is probably not the initiating event in Parkinson’s disease, but it is important for the neurodegeneration that follows. 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,” concluded Dr. Tansey.