Neural cell transplants may be potential therapy for Parkinson's disease

Washington, May 19 : Four primate studies have shown the possibility that neural cell transplants may be a potential therapy to treat neurodegenerative disorders like Parkinson's disease.

In one study, the ability of transplantation of human neural progenitor cells (hNPCs) to produce glial derived neurotrophic factor (GDNF) in the brain was investigated.

"Localized delivery is essential for aiming therapeutic molecules when treating neurodegenerative disorders. There are currently a number of clinical trials underway using direct gene therapy approaches to deliver potent trophic factors throughout the basal ganglia," said Dr. Maria Emborg of the University of Wisconsin-Madison.

The research team found that hNPCs genetically modified to over-express GDNF were able to survive transplant and produced GDNF for three months.

They also observed that the functional recovery in test animals had increased, and that the transplant procedure did not leave any side effects.

Another team of experts from the University of Kentucky Medical Center and the Shandong Provincial Hospital, Shangdong, PR of China, is studying the neurorestorative effects of the exogenous protein neurturin (NTN), another member of the GDNF family.

The researchers say that the protein may have beneficial effects on Parkinson's disease, for their research has so far shown some restorative influences after cell transplantation.

"Tissue distribution of trophic factor is a critical variable to achieve optimal effects on dopamine function and promote behavioral improvement. The volume of GDNF distribution in the trophic factor recipients significantly correlated with motor function improvements. Tissue distribution may not have been optimal with NTN, but the overall effects of NTN on motor and dopaminergic function suggest potential therapeutic uses," said corresponding author Dr. Richard Grondin of the University of Kentucky.

Dr. Zhiming Zhang of the University of Kentucky College of Medicine said that their study reports on attempts at monitoring GDNF-induced functional changes in the basal ganglia using pharmacological MRI (phMRI) to measure response to dopamine.

The researchers said that the objective behind the study was to be able to visualise changes in the living brains of Parkinson's disease.

"Our hypothesis was that phMRI techniques combined with selective dopaminergic agents could monitor PD treatment. GDNF has been proven to halt or reverse progressive degeneration of the nigrostriatal DA system in models of PD. The ability to reliably monitor therapeutic effects would provide valuable information in assessing the progression of PD," said Zhang.

The research team observed that phMRI "showed its potential" by detecting functional changes before and after infusion with GDNF, and that such changes were accompanied by improvements in motor function.

Another research team tested the transplantation of dopamine neurons as therapy for PD. The main objective of the study was to determine where to place the transplanted neurons to gain the best environment for the optimal effect.

It was found that grafted dopamine neurons could "extend neurites toward a desired target over several millimeters through the brain in animal models..." which favours the prospect of "circuit reconstruction from grafted neurons placed at appropriate locations in the neural circuitry."

Corresponding author John Sladek at the University of Colorado School of Medicine said that test results suggested that substantia nigra grafts could send targeted DA neurons to a location where they could survive and extend neurites over longer distances.

"Survival of the grafts and extension of the axons is of importance because it positions the DA neurites to grow in a trajectory toward the striatum, using the striatal grafts as an attractant," said Sladek.

Dr. Jeffrey Kordower of the Rush University Medical Center, Chicago, said: "Taking these four papers together we can see that primate studies are helping to elucidate the likelihood of favorable outcomes following stem cell transplantation with respect to route of administration, possible modes of action and the ability to track the effects."

An article describing the four studies has been published in the journal Cell Transplantation.

ANI