Growth Factor Promotes New Neuron Growth in Mouse Model of Parkinson's Disease

A well-known growth factor has been shown to increase the growth of new neurons in mice induced to develop Parkinson's disease. The finding highlights a potential new therapy for the condition.

Newswise — Mice induced to develop Parkinson’s disease (PD) show an increase in the growth of new neurons after they are treated with a well known growth factor. The research, to be published May 16 in The Journal of Neuroscience, based on work by scientists at the Buck Institute, highlights a potential new therapy for this incurable, neurodegenerative disorder that affects 1.5 million Americans.

The mice, which developed Parkinson-like symptoms after they received the toxin MPTP (which causes PD in humans) were treated with fibroblast growth factor-2 (FGF-2), a naturally occurring protein that has been studied extensively for its neuroprotective properties. In the Buck study, the use of FGF-2 enhanced the neurogenesis, or growth of new neurons, that was already underway in the injured area of the brain. In addition, researchers began to see an increase in the cells that produce dopamine, the neurotransmitter implicated in PD.

“The fact that FGF-2 allowed these new neurons to develop in the principle site of cell loss in the disease is quite exciting,” said Buck faculty member and lead scientist Julie Andersen, PhD. “This suggests that administration of growth factors might be used therapeutically to replace dead or damaged cells. The next step in our research is to see whether treatment with FGF-2 results in any symptomatic improvement in the mice.”

Scientists at the Buck are currently researching FGF-2 as a potential treatment for Huntington’s disease, a fatal hereditary brain disorder that affects approximately 30,000 Americans. In partnership with Neurobiological Technologies, Inc. (NASDAQ: NTII), Buck researchers are seeking to create a form of FGF-2 for human clinical trials. The protein shows particular promise because it is able to cross the blood-brain barrier.
This most recent study highlights the interdisciplinary approach to research at the Buck Institute. This work built on earlier discoveries in the laboratory of David Greenberg, MD, PhD, which showed neurogenesis occurring in the brains of patients diagnosed with Alzheimer’s disease, and the laboratory of Lisa Ellerby, PhD, which showed that FGF-2 promoted new nerve growth and increased survival in mice genetically engineered to develop Huntington’s disease. The work as a whole emphasizes a research focus at the Buck Institute on efforts to enhance the brains ability to heal itself in the face of injury.

Joining Andersen in the study were Jun Peng, Lin Xie, Kunlin Jin, and David A. Greenberg, all of the Buck Institute.
The Buck Institute is an independent non-profit organization dedicated to extending the healthspan, the healthy years of each individual’s life. The National Institute of Aging designated the Buck a Nathan Shock Center of Excellence in the Biology of Aging, one of just five centers in the country. Buck Institute scientists work in an innovative, interdisciplinary setting to understand the mechanisms of aging and to discover new ways of detecting, preventing and treating age-related diseases such as Alzheimer’s and Parkinson’s disease, cancer, stroke, and arthritis. Collaborative research at the Institute is supported by genomics, proteomics and bioinformatics technology. For more information: www.buckinstitute.org.

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New Treatment Tried For Parkinson's Disease

Like many patients with Parkinson’s disease, over time, medicine becomes less effective. Doctors are now using a new approach.
In the lab they’ve developed a fluid that’s injected directly into the patient’s brain. The fluid contains billions of viruses and delivers a gene that re-establishes some of the normal chemistry in the brain.
This is the first study to use gene therapy on advanced cases of Parkinson’s and early results are impressive. 
Twelve patients were injected with the genes initially and while all of them got better, nearly half showed a surprising response. The patients became more mobile. They were more able to live independently and tremors improved.
Even more promising, one year after the injections, the majority of patients continued to improve, hinting that their brains may actually be trying to reverse the damage caused by the disease.
The next step for this treatment method is a larger study.

Cell-Based Therapy Shows Promise In Patients With Parkinson's Disease

A novel cell therapy using retinal pigment epithelial (RPE) cells attached to tiny gelatin bead microcarriers implanted in the brain can improve the symptoms of patients with moderate to advanced Parkinson's disease (PD).
Rush University Medical Center neurosurgeon Dr. Roy A. E. Bakay and colleagues from Emory University, Atlanta found the therapy Spheramine was well-tolerated and patients experienced improvement in Parkinsonian symptoms (tremor, rigidity, slowness of movements, and impaired balance and coordination.) These findings were presented at the Annual Meeting of the American Association of Neurological Surgeons in Chicago on April 28, 2008.
The pilot study was initiated at Emory University Hospital and followed six patients with moderate to advanced PD to investigate the safety, tolerability, and efficacy of the Spheramine implantation. The full patient group has been evaluated for four years, and several have been monitored for six years. Bakay and colleagues report long-term improvement or stabilization of symptoms, maintained for a minimum of two years after Spheramine implantation. They note no Spheramine-related serious adverse events were reported and that the most frequent adverse event was postsurgical headache, which spontaneously resolved within one to two weeks.
"The results of this study are very encouraging - Spheramine is well tolerated through several years of follow-up and improvement in parkinsonian symptoms is sustained," stated Bakay.
The cellular product Spheramine consists of RPE cells attached to microcarriers. RPE cells produce levodopa, the precursor of dopamine. Dopamine is a neurotransmitter produced by nerve cells in the brain that progressively declines as the disease progresses.
The RPE cells, which are normally found in the back of the eye, are cultured under standardized conditions and attached to the microscopic beads prior to implantation. The microcarriers are necessary for the cells to survive in the brain. The implanted cells serve as a new potential source of levodopa to enhance dopamine production where it is most needed.
The patients were selected based on disease stage, levodopa responsiveness, and severity of PD symptoms while off medication. An even distribution of Spheramine was surgically implanted into the more affected side of the brain, and patients left the hospital a few days later.
The primary efficacy measure in this trial is the motor score of the Unified Parkinson's Disease Rating Scale (UPDRS) when the patient has been OFF antiparkinsonian medication for at least 12 hours. The researchers report clinical improvements were noted in both UPDRS motor scores off medication (44 percent improvement from baseline at 48 months) and patient-reported quality of life scores (23 percent improvement from baseline of total PDQ-39 score at 48 months). Several of these patients have been monitored for 6 years and the trial has been extended to 10 years of follow-up."
Bakay said positive results in the pilot study prompted the initiation of a Phase IIb, multicenter, double-blind, randomized, sham surgery-controlled study (STEPS) to further evaluate the safety, tolerability and efficacy of Spheramine. Changes from the pilot study included implantation in both sides of the brain and the addition of a sham surgery group. To date, 71 patients have been randomized for either Spheramine or sham surgery and results from the will become available later this year.
Parkinson's Disease
Parkinson's disease is a progressive brain disorder that affects a person's motor skills which worsen as the disease advances. Early in the disease, there is a loss of brain cells that produce the chemical dopamine. Normally, dopamine operates in a delicate balance with other neurotransmitters to help coordinate the millions of nerve and muscle cells involved in movement. Without enough dopamine, this balance is disrupted, resulting in tremor (trembling in the hands, arms, legs and jaw); rigidity (stiffness of the limbs); slowness of movement; and impaired balance and coordination - the hallmark symptoms of PD.
PD affects one in every 100 people over the age of 65. The latest epidemiology studies indicate that worldwide numbers will increase from an estimated 4.1 million in 2005 to 8.7 million people with PD by 2030. There were an estimated 19,500 PD-related deaths in the United States in 2005, an increase of 1,500 deaths from 2004.
It is estimated to cost $23 billion a year in direct and indirect costs and lost productivity. Despite therapeutic advancements, oral medications provide insufficient symptom control after the disease has progressed and new approaches are needed.
Rush University Medical Center