GM 608 in A Phase IIA Pilot Double-blinded, Randomized, Placebo Controlled Trial in Mild to Moderate Parkinson Disease

Background The investigational drug GM608 is a synthetic oligopeptide containing 6 amino acids with a sequence identical to one of the active sites of human Motoneuronotrophic factor (MNTF), also referred to as GM6 in studies. MNTF is a novel human endogenous developmental stage neurotrophin for the nervous system with a specific human chromosome location.

The investigators' preclinical animal study has shown that intravenously injected GM608 is able to penetrate the blood-brain barrier and enter the brain. GM608 has shown neuroprotection in a variety of in vitro and animal models of numerous Central Nervous System (CNS) diseases including ischemic stroke, spinal cord injury, Parkinsons Disease (PD), amyotropic lateral sclerosis (ALS), multiple sclerosis (MS), Alzheimer's Disease (AD) and Huntington Disease (HD). In particular, the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 6-hydroxydopamine (6-OHDA) mouse model for PD all showed GM608 has neuroprotective effect. GM608 also enhanced neuron cell survival very significantly in the cerebrospinal fluid (CSF) of patients with Huntington disease, MS, Stroke, Parkinson, Alzheimer and ALS.

This pilot trial is designed to test proof of principle, i.e. determine if a 2-week treatment with this agent can restore the nonfunctioning nigral dopaminergic neurons in PD over a 3month period, during which the placebo-treated arm is expected to have little or no worsening of the total UPDRS score compared to baseline. A Phase 1 Clinical Trial Study has been completed. The Phase 1 Trial primary objective is to determine the safety and tolerability and to establish the pharmacokinetic and pharmacodynamic properties of GM608 at 0.5, 1.5, and 5.0 mg/kg administered as a single bolus intravenous dose in human subjects and after 3 consecutive daily doses of GM608 at the highest safe and tolerated dose of 5.0 mg/kg. The Phase 1 study established that 3 consecutive daily doses of 5.0 mg/kg of GM602 are safe and tolerated.

Mechanism of Action Motoneuronotrophic factor (MNTF) is highly specific to the human nervous system. It is expressed rapidly during the first trimester of human fetal development, peaking at week nine. MNTF is a developmental stage regulatory (antisense) neuro-signaling molecule that binds perfectly on very specific receptors. Using In Silico Analysis, Genervon identified and developed as a drug candidate one of the active sites of MNTF, an analog of six amino acids named GM608.

In the investigators' testing for efficacy in Parkinson disease MPTP and 6-OHDA animal models, GM608 demonstrated a dose dependent attenuation of PD in the mice with 20 mg/kg showing the most efficacious. Behavioral, biochemical and histological analysis demonstrated the attenuation illustrating a unique effect for GM608 in PD. These data suggest that GM608 is effective in the mouse model of PD following IV injection and may be a potential treatment for PD patients.