Potential New Drug Shows Promise for Neuroprotection

In tests on a mouse model of Parkinson’s disease (PD), an experimental drug in the early stages of development prevented damage to dopamine neurons by protecting them from inflammation. The results appear in the December 16 edition of the Journal of Neuroscience.

The immune system normally defends a person’s body from infection and injury. But sometimes it unnecessarily goes on high alert, which leads to inflammation. In PD, inflammation may speed up the death of dopamine neurons in the brain — the cells that help control the body’s movements. Specifically, inflammation happens when immune cells in the brain (microglia) become activated, and other immune cells (T cells) attack dopamine neurons.

To try to treat inflammation in PD, researchers at the University of Nebraska Medical Center in Omaha, NE, took advantage of a naturally occurring anti-inflammatory molecule called vasoactive intestinal peptide (VIP). They knew that VIP could not be used as a PD therapy because it activates both good and badinflammatory responses and because it leaves the body too quickly to be therapeutic. So they created molecules similar to VIP but with improvements, and tested them in mice with PD-like brain changes and symptoms.

Results

  • Of the molecules tested, one (LBT-3627) protected up to 80 percent of dopamine neurons in the brains of mice with PD-like brain changes. It also lasted much longer than VIP in the body before being broken down.
  • The drug LBT-3627 also decreased inflammation caused by immune cells.
  • The same molecule LBT-3627 seemed to work by targeting a receptor on T cells known as VPAC2, and by binding to this receptor, it changed the behavior of the T cells from inflammatory to protective.

What Does It Mean?

Therapies that provide neuroprotection — the ability to slow or stop the loss of dopamine neurons in the brain, which underlies PD are urgently needed. Recently, the role of inflammation in PD has drawn interest in the scientific community. If indeed there is an “exaggerated response” of the immune system in PD (meaning it overreacts), then therapies which modify the response may help slow down PD. The results of this early-stage study with laboratory mice suggest that LBT-3627, being developed by Longevity Biotech, Inc., may hold promise for providing neuroprotection by fighting inflammation in the brain.

However, questions remain. The role of the immune system in PD is not very well understood. The role of VIP, the molecule the novel drug imitates, is also not completely known. Whether this molecule LBT-3627 would be helpful in treating people with PD is unknown. For instance, will it be able to cross the blood brain barrier and allow for delivery as an injection or will surgery need to be performed to allow direct delivery to the brain? If further laboratory studies achieve similarly successful results and are able to answer other questions, a phase 1 clinical trial — a test for safety in a small number of study participants — could launch as soon as 2017.

Reference

Olson KE, Kosloski-Bilek LM, Anderson KM, Diggs BJ, Clark BE, Gledhill Jr. JM, Shandler SJ, Mosley RL, Gendelman HE. (2015). Selective VIP Receptor Agonists Facilitate Immune Transformation for Dopaminergic Neuroprotection in MPTP-Intoxicated Mice. J Neuroscience 35(50): 16463-16478. DOI:10.1523/JNEUROSCI.2131-15.2015 http://doi.org/10.1523/JNEUROSCI.2131-15.2015

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