Sangamo BioSciences, Inc. announced the publication of preclinical data demonstrating protection of nerve tissue and functional improvements in motor symptoms in a validated rat model of Parkinson Disease (PD) using Sangamo's Zinc Finger Protein (ZFP) technology.

As previously disclosed, the study was supported by funding from The Michael J. Fox Foundation for Parkinson's Research (MJFF). The data described in the publication were part of a successful application for a second round of funding from MJFF to support the progress of a ZFP approach in a non-human primate model which is the next stage of development for this ZFP Therapeutic to treat PD.

The work, which was carried out in collaboration with scientists from the laboratory of Krystof Bankiewicz, MD, PhD, professor of Neurosurgery and Neurology at the University of California, San Francisco (UCSF) was published on December 8, 2010 in the Journal of Neuroscience.

“We are enthusiastic about the success of this novel ZFP Therapeutic approach to date and hopeful that its further development can take us closer to our goal of delivering Parkinson's patients better treatment options,” said Todd Sherer, PhD, Chief Program Officer at MJFF.

Sangamo has developed Zinc Finger DNA-binding Protein Transcription Factors (ZFP TFs) to activate the expression of Glial cell line-Derived Neurotrophic Factor (GDNF), a potent neurotrophic factor that has shown promise in preclinical testing to slow or stop the progression of PD. The data published in the Journal of Neuroscience demonstrated that ZFP TF activation of GDNF expression was achieved genome-wide with exquisite specificity and was neuro-protective, resulting in positive functional improvements in assays of motor impairment in a rat model of PD.

Sangamo's technology platform permits the development of highly specific ZFP TFs that can be used to regulate genes at the DNA level. Using a ZFP TF, a gene can be activated in a patient's own cells in its natural cellular context. Use of a ZFP TF to activate the gene in the brain — as compared to addition of a cDNA or the recombinant protein — allows the delivery of a more physiologically relevant dose of the native gene product which may be a safer and more effective alternative. This is of particular significance when targeting potent natural growth factors such as GDNF, where sufficient but not super-physiological levels of the therapeutic protein are required to achieve efficacy.

“Publication of these data is an important validation of the potential therapeutic applications of our ZFP technology,” said Edward Lanphier, Sangamo's president and CEO. “We are developing a portfolio of ZFP TF gene regulation programs focused on neurologic indications and our PD program is an important part of our preclinical pipeline.  ZFP TF-driven gene activation is the underlying mode of action of our lead ZFP Therapeutic (SB-509) which is being evaluated in a phase II b clinical trial (SB-509-901) for diabetic peripheral neuropathy and has demonstrated both clinical efficacy and an excellent safety profile. Preclinical success in PD models with the ZFP TF activator of GDNF will support the evaluation of this approach in clinical trials.  Moreover, it would demonstrate the potential for ZFP TF use in the brain and set the stage for the further application of our technology platform to other genes that may have a therapeutic benefit in PD and other neurologic indications.”

“An Engineered Zinc Finger Protein Activator of the Endogenous Glial Cell Line-Derived Neuro-trophic Factor Gene Provides Functional Neuro-protection in a Rat Model of Parkinson's Disease.”

Parkinson's disease is a chronic, progressive disorder of the central nervous system and results from the loss of cells in a section of the brain called the substantia nigra. These cells produce dopamine, a chemical messenger responsible for transmitting signals within the brain. Loss of dopamine causes critical nerve cells in the brain, or neurons, to fire out of control, leaving patients unable to direct or control their movement in a normal manner.

The symptoms of Parkinson's may include tremors, difficulty maintaining balance and gait, rigidity or stiffness of the limbs and trunk, and general slowness of movement (also called bradykinesia). Patients may also eventually have difficulty walking, talking, or completing other simple tasks.

Symptoms often appear gradually yet with increasing severity and the progression of the disease may vary widely from patient to patient. There is no cure for Parkinson's disease which affects nearly 5 million individuals worldwide. Drugs have been developed that can help patients manage many of the symptoms; however, they do not prevent disease progression.

Founded in 2000, The Michael J. Fox Foundation is dedicated to finding a cure for Parkinson's disease through an aggressively funded research agenda and to ensuring the development of improved therapies for those living with Parkinson's today. The Foundation has funded over $221 million in research to date.

Sangamo BioSciences, Inc. is focused on research and development of novel DNA-binding proteins for therapeutic gene regulation and modification. The most advanced ZFP Therapeutic development program is currently in a phase II b clinical trial for evaluation of safety and clinical effect in patients with diabetic neuropathy and a phase II trial in ALS.