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Cogane™ Parkinson's Disease
Parkinson's disease is a movement disorder characterised by muscle rigidity, tremor and a slowing of physical movement (bradykinesia) and, in extreme cases, a loss of physical movement (akinesia).The primary symptoms are the result of altered signalling of an area of the brain, the striatum, responsible for the control of movement. This is caused by degeneration of dopaminergic neurones between the striatum and the substantia nigra part of the brain leading to insufficient formation and action of dopamine. Parkinson's disease is therefore termed a neurodegenerative disease. The disease is slow in onset and the appearance of symptoms reflects the gradual loss of dopaminergic neurones.
Huntington's disease results from genetically programmed degeneration of neurones which causes uncontrolled movements. loss of intellectual faculties and emotional disturbance. Specifically affected are the cells of the basal ganglia, structures deep within the brain that have many important functions, including movement. Huntington's disease is a familial disease, passed from parent to child through a mutation in the normal gene.
Mode of action
CoganeTM is a novel small molecule, orally bioavailable neurotrophic factor inducer that readily crosses the blood brain barrier. In preclinical models, CoganeTM stimulates the release of neurotrophic factors and increases neurite outgrowth. Importantly, CoganeTM also reverses the decrease of neurotrophic factors and reverses dopaminergic neurnal degeneration observed in vitro. WWhe administered orally in severaldifferenct preclinical models of Parkinson's disease CoganeTM reverses the loss of dopaminergic neurones and elevates glial derived neurotrophic factor (GDNF)
GDNF has been shown to be particularly effective in re-growing damaged nerves. Since GDNF is a protein, it cannot be given orally (in tablet or liquid form) because it is degraded in the stomach and intestine, and also does not readily cross the blood-brain barrier. GDNF can work only when injected into or when produced inside the brain. Direct injection of GDNF into the area of the brain involved in Parkinson's disease has shown evidence of being clinically effective in restoring the control of movement but requires highly complex and difficult surgical procedures. CoganeTM, which can be taken orally, readily crosses the blood-brain barrier and in preclinical models has been shown to stimulate the release of GDNF in the brain and therefore has the potential to overcome many of the difficulties associated with GDNF administration.
Other degenerative diseases
The neuroprotective and neurotrophic actions of CoganeTM suggest potential beneficial effects in other neuro-degenerative diseases including Alzheimer's disease and Hintington's disease. In our clinical study of CoganeTM in mild and moderate Alzheimer's disease patients, the more moderate Alzheimer's disease patients showed a decline in cognition in the placebo group with an encouraging trend for slower disease progression in the CoganeTM treated group. Patients with a mild form of the disease showed no decline in cognitive function and therefore, there was no effect detectable with CoganeTM.
The benefits to the moderate Alzheimer's disease patients, coupled with Cogane'sTM good safety profile and tolerability, provides positive data for longer term studies for efficacy determination in both Parkinson's disease, Alzheimer's disease and Huntington's disease.
Progress to date
We have made significant progress demonstarting that in preclinical models of Parkinson's disease CoganeTM reverses the damage to dopamine-containing neurones and elevates GDNF in the area of the brain involved in Parkinson's disease. In a recently completed efficay study, oral administration of CoganeTM over eighteen weeks significantly reduced parkinsonian disability by 43 % in the macaque model of MPTP-induced Parkinson's disease (the gold standard for preclinical Parkinson's disease research), which will be clinically highly relevant if repeated in Parkinson's disease patients. Encouraginly, in this study a statistically significant reduction in parkinsonian symptoms was reached after nine weeks of administration with CoganeTM. The magnitude of the effect increased over the subsequent nine weeks of administration and was still increasing at the end of the study (week eighteen).
We have also recently completed a Phase Ib stafety, tolerability and pharmacokinetic clinical study with CoganeTM, which was shown to be safe and generally well tolerated in both healthy volunteers and Parkinson's disease patients over the twenty eight day study period. Importantly at date twenty eight, plasma levels in Parkinson's disease patients taking CoganeTM at a dose of 150 mg/day reached levels associated with efficay in the nonclinical efficacy study.
In July 2009, CHDI Foundation Inc., in the USA entered into an agreement to evaluate the efficacy of CoganeTM in a preclinical model of Huntington's disease. CHDI is funding the testing of CoganeTM (in it network of industrial contract research organisations) employing its standardised criteria for the rigorous evaluation of novel thereapeutic approaches for Huntington's disease treatment.
