GM604 is an endogenous human embryonic stage neural regulatory and signaling peptide that controls the development, monitoring and correction of the human nervous system. Neurological diseases are multisystem, multifactorial, and single target drugs are ineffective. Genervon's Master Regulators play a significant role in embryonic/fetal nervous system development and are potent disease modification drug candidates modulating many pathways including inflammation, apoptotic, and hypoxia. The study drug is an regulatory peptide with a sequence identical to one of the active sites of human Motoneuronotrophic Factor and is manufactured by solid phase synthesis. Pre-clinical research indicates it to be a neuro-protective agent in animal models of ALS, motorneuron diseases, PD, other neuro-degenerative diseases and stroke. GM604 controls and modulates over many known and significant ALS genes with positive effects interactively and dynamically through multiple pathways, and up to twenty-two biological processes, including neuro-protection, neurogenesis, neural development, neuronal signaling, neural transport, and other processes. GM6 is not a cocktail of drugs, but one master regulator peptide drug that functions through multiple pathways. Genervon hypothesized that studying the biomarkers of protein expressions of these ALS genes such as superoxide dismutase 1 (SOD1) and the protein expression of substances such as tau, neurofilament - heavy (NF-H), Cystatin C which were indications of degeneration of neuron in the CSF collected from ALS patients will provide information of the possible GM604's mechanisms of action in treating ALS. 1. This pilot trial is designed to test proof of principle, i.e. determine if a 2-week IV bolus treatment with this agent can (1) change ALS protein expression (target biomarkers and efficacy biomarkers) after treatment (2) have preliminary effects measures of ALS disease clinical progression. Study Objectives are: 1. To test the safety and tolerability of GM604 in a population of ALS patients. 2. To test for changes in ALS biomarkers before and after treatment. 3. To determine preliminary effects of injections of GM604 on measures of ALS disease biomarkers and clinical progression
Name: GM604
Name: Placebo comparator
Description: Efficacy by percent change in biomarker in the CSF at week 12 from baseline: (a) Efficacy biomarkers (b) Target biomarkers (c) Efficacy/target biomarkers
Measure: Efficacy by percent change in biomarker in th CSF at week 12 from baseline Time: baseline, week 2, week 12Description: Safety: 1. adverse event frequency and severity, changes in vital signs, clinical laboratory values. 2. Serious adverse event frequency
Measure: Safety by measuring 1. adverse event frequency and severity, changes in vital signs, clinical laboratory values. 2. Serious adverse event frequency Time: baseline, week 2, week 12Description: Tolerability: The ability to complete the first 2 weeks of active treatment in the study
Measure: Tolerability by measuring the ability to complete the first 2 weeks of active treatment in the study Time: Baseline, week 2, week 12Description: Progressive change in ALSFRS-R of each patient determined from the following data points:1) symptom onset, 2) baseline, 3) end of week 2 examination, 4) end of week 6 examination and 5) end of week 12 examination.
Measure: ALSFRS-R (Amyotrophic Laeral Sclerosis Functional Rating Scale - Revised) Time: Symptom onset, screening, baseline, week 2, week 6, week 12Description: Progressive change in Forced Vital Capacity (FVC) from the following data points: 1) symptom onset, 2) baseline, 3) end of week 2 examination, 4) end of week 6 examination and 5) end of week 12 examination.
Measure: Forced Vital Capacity (FVC) Time: Symptom onset, baseline, week 2, week 6, week 12Description: Progressive change in Forced Vital Capacity (FVC) from the following data points: 1) symptom onset, 2) baseline, 3) end of week 2 examination, 4) end of week 6 examination and 5) end of week 12 examination.
Measure: Time Up and Go (TUG) Time: Symptom onset, baseline, week 2, week 6, week 12Description: Progressive muscle strength change measured by HHD (handheld dynamometry testing score) from the following data points: 1) symptom onset, 2) baseline, 3) end of week 2 examination, 4) end of week 6 examination and 5) end of week 12 examination.
Measure: muscle strength Time: Symptom onset, baseline, week 2, week 6, week 12Description: Percentage changes in Biomarkers in blood between baseline and 1) the end of week 1, 2) end of week 2, 3) end of week 6 and 4) end of week 12. Comparing the changes encompassing the entire cohort of 10 subjects.
Measure: Biomarker in blood Time: baseline, week 2, week 6, week 12Description: Report all death as mortality rate
Measure: Mortality rate Time: baseline, week 2, week 6, week 12Description: Secondary analyses may consider a comparison of slopes (change in the rate of decline) for any hint of disease modification using placebo outcomes in patients matched for baseline features from a large database of recent clinical trials by NEALS showing stable rates of decline as historical controls.
Measure: comparison of slopes (change in the rate of decline)of disease progression Time: Symptom onset, baseline, week 2, week 6, week 12Description: Secondary analysis to allow a-priori stratification of patients by their symptoms if available predominantly lower motor neuron predominantly upper motor neuron predominantly bulbar
Measure: stratification of patients by symptoms Time: Symptom onset, baseline, week 2, week 6, week 12Allocation: Randomized
Parallel Assignment
There is one SNP
In ALS model, SOD1 mice from Jackson Lab stock #G93A were treated with GM604 at 0, 1 and 5 mg/kg. --- G93A ---