Parkinson's Disease and Neurodegenerative Disorders
Parkinson’s disease results when there is significant loss of dopaminergic neurons in the substantia nigra of the midbrain. Most people (men in particular) above the age of 80, have some element of parkinsonism – both natural and possibly drug induced. With aging and chronic neurodegeneration, there is neuronal loss and when the dopaminergic pathways from the midbrain to the basal ganglia become significantly degraded – patients start manifesting with symptoms of Parkinson’s disease.
Parkinson’s disease clinically presents with bradykinesia (slowed movements), rigidity in tone, pill rolling tremors, gait imbalance, changes in speech/handwriting and cognition. In essence, it is a neurodegenerative disease in and of itself and seems to be caused by aging – chronic neurodegeneration. Michael J Fox, is unusual in his early age onset – some have theorized that here may have been some sort of drug use involved during the shoot of the movie “Doc Hollywood” that caused Michael J. Fox’s parkinsonism or MJF started exhibiting symptoms around then – depression and changes in behavior/personality. I personally have seen young people who abused pure MDMA (the active ingredient in ecstasy) and developed drug induced parkinsonism.
` Regardless of the cause, the traditional treatment for parkinsonism is symptom relief – i.e. if parkinson’s is caused by a loss of dopaminergic input – replacement of dopamine with exogenous dopaminergic agents (levodopa/carbidopa) should help. And so Sinemet was made – to replace the dopamine lost naturally. And while sinemet is an amazing drug – it has some nasty side effects and over time – its effectiveness wears down. Other agents came into play to allow dopamine a longer time in the system (entacapone), dopamine agonists – all of which may help with parkinson’s. Over time, patients can start developing on/off periods – when they are on (i.e. after taking their dopaminergic agents) – they may exhibit dyskinesias, tremors, etc. When they are off (when the agents wear off) – they are frozen – bradykinetic.
It’s a tough course to watch over years and years. End stage parkinsonism is the worst – patients become prisoners trapped in their own bodies. They cannot move, they cannot eat well/swallow well, they have pain, they have poor airway protection due impaired cough reflex. Most patients with parkinson’s die of pneumonia in the end stages of the disease – its horrible.
This is why today’s news of 2-73 efficacy to support potential disease modification in Parkinson’s disease is huge. We may have a breakthrough as nothing right now available is out there that can change the pathophysiological process in Parkinson’s disease. All we do now is symptom management but the end result is always the same – Parkinson’s patients will get worse. If 2-73 somehow can halt the ongoing neurodegenerative process through its sigma 1 receptor agonism (which, I believe halts chronic neuroinflammation) – perhaps 2-73 and 3-71 may be able to stop the disease from worsening – stopping it in its tracks.
This is why I have posted many times in the past that what I think Anavex has – a platform drug that is safe/tolerable and acts in the herald stages of a complicated neuroinflammatory cascade. The neuroinflammatory cascade seems to be a commonality in terms of the pathophysiology of most neurodegenerative disorders – AD, PD, certain types of epilepsies, Retts, Fragile X, etc. With each piece of data that comes out in the open, more and more evidence builds towards a paradigm shift. Thing is - the science isn't proven and it considered to be "different" and unfamiliar in the approach being taken when larger pharma companies take the conventional approach (and demonstrably a failure of an approach) in terms of stamping out diseases like AD. One thing about science: major advancements are made when the renegades of the time and place inject new ideas that finally break through and cause a paradigm shift and paradigm shifts take time. The only thing long investors should have if they have the courage of their own investment decision is patience. Patience is a virtue and cannot be stated enough times.
