Genervon's scientists confirmed the mechanism of action (MOA) of ALS. GM604 controls over 4,000 genes, and modifies ALS disease progression by modulating 8 or more pathways involving up to 22 biologic functions concurrently and dynamically: 1. Insulin Receptor binding for ALS therapeutic effects. 2. Free Radical damages reduction for inhibition of ALS apoptosis. 3. PIP3 Kinase Activation for neuroprotection against ALS. 4. Bax inhibition reduced neuron death caused by ALS. 5. Akt activation to suppress SOD1 expression which caused ALS disorder. 6. Hypoxic response normalization to prevent ALS degeneration. 7. DNA repair capability increase against ALS neuron apoptosis. 8. Axonal transport stimulation to delay ALS onset
GM604 also proved to be quite effective in the disease modification of ALS in ALS animals with mutant SOD1. It led to an improved clinical score in SOD1 mice (p<0.001 for all groups compared to control). Moreover, GM604 delayed the onset of ALS symptoms by 27%, extended life by 30% and delayed the median clinical score deterioration time in ALS mice by 41%.
GM604 also provided neuroprotection against soluble inflammatory factors from ALS human patients' Cerebral Spinal Fluid (CSF) in vitro by 175%. GM604 dramatically increased the survival life span by 500% (6 fold from 7-14 weeks to 55-65 weeks) and increased of preservation of motor neurons by 160% (2.6 fold) in a Wobbler Mice Model for motoneuron diseases such as ALS.
The design of optimal therapeutics by discovery of endogenous embryonic stage human master regulators is changing from hitting single pathways to a more comprehensive and dynamic approach addressing the complexity of neuro-degenerative disease. Genervon has a family of highly specific drug candidates that addresses this complexity, and believes it is at the forefront of a shift that is only beginning to be appreciated.
Stroke is the third leading cause of death in the United
affecting approximately 700,000 people per year. The estimated cost to
the healthcare system is $73 billion annually. Approximately 80% of
strokes are ischemic.
Ischemic strokes are caused by a blockage of the blood flow to the
brain. This may be caused by a number of factors, including a blood
clot or narrowing of the arteries due to build up of fatty material.
The molecular chain of events following an ischemic stroke is a
multifactorial process involving multiple signaling pathways. The ideal
stroke therapeutic would target multiple parts of this cascade and have
anti-inflammatory, anti-apoptotic and anti-oxidant properties. Previous
clinical attempts to develop drugs for stroke through targeting single
specific processes, such as free radical scavengers (Cerovive; Renovis)
or NMDA antagonism (Cerestat; Boehringer Ingelheim), have not been
Currently only one FDA-approved ischemic stroke therapeutic is on the
market, Activase (Genentech). This drug works by degrading the clot and
has no direct impact on other pathological processes associated with
the ischemia. In addition, its use is limited to administration within
three hours of the incidence of the stroke, leading to only 4% of acute
stroke patients receiving the drug.
Through in vitro and in
vivo studies, GM6 has demonstrated its ability to affect the expression
of numerous genes, including those involved in neurogenesis, neural
development and neural signaling. These findings indicate that GM6 may
function as a master switch that signals through multiple neural
pathways, such as PI3 kinase.
In a study published in
Brain Research, GM6 demonstrated its ability to exert neuroprotective
effects in a mouse model of stroke. In this study, GM6 was found to
increase neurogenesis as well as decrease apotosis and inflammation in
the mouse brain. In addition, GM6 was able to penetrate the blood-brain
Further research has also
found that GM6 induces the expression of anti-inflammatory,
anti-apoptotic and anti-oxidant proteins. These are important
neuroprotective proteins with application for the treatment of acute
Due to its neurologically
active properties, Genervon is also conducting preclinical research
exploring the use of GM6 to treat other neurological disorders. In a
variety of in vitro and in vivo models, GM6 has shown neuroregenerative
and neuroprotective properties. MNTF has been shown to have
neuroprotective and anti-apoptotic properties as well and may play a
role in stem cell differentiation into motoneurons.
These findings indicate
that GM6 is a promising treatment for Parkinson’s disease,
Alzheimer’s disease, spinal cord injuries, amyotrophic
lateral sclerosis (ALS), multiple sclerosis (MS) and