An Excited Epileptologist's Saturday Rant
Note that the prose below is my own opinion and you should do your own due diligence regarding this company.
Epilepsy, a disorder of the brain that causes people to be at increased risk for recurrent, unprovoked seizures burdens those who suffer from it with disabilities that most cannot see. And with this lack of understanding (seeing is believing, right?), epilepsy is a common neurological disorder that most of the lay public have no idea about other than the vague understanding that seizures are “when people shake.”
In my work as a young epileptologist forever honing my art as a clinician, I empathize with my patients and with those who suffer from epilepsy tremendously. Their seizures act as handcuffs and leg shackles, keeping these sufferers from living the quality of life that they deserve and have the potential of achieving. An epileptic seizure – a sudden, hypersynchronous and excessive discharge of electrical activity within a region of the cerebral cortex or the whole cortex itself, often occurs randomly and without warning. For this reason, many patients feel humiliated when seizures rear their ugly heads at the wrong times – forcing many to stay behind closed doors. In addition to the lack of general understanding among the general populace, most physicians, including many general neurologists, do not know how to properly diagnose, manage and treat patients with epilepsy. For this reason, many epileptic patients never achieve full seizure control (i.e. no seizures) and never reach the potential quality of life they may be capable of reaching, with the proper care. My role as a clinical epileptologist in NJ is to serve the community with the expertise required to properly treat epileptic patients so that they may achieve the quality of life they deserve.
Epilepsy is not just about seizures. It is a syndrome which Google officially defines as a group of symptoms that consistently occur together or a condition characterized by a set of associated symptoms. Seizures are just a part of the syndrome but other aspects included in the syndrome are: personality/mood changes, changes in energy/sleep, cognitive changes, endocrine disorders, etc. It is the role of an epileptologist to not only manage an epileptic patient’s seizures but to also assist in the other aspects of the epileptological syndrome.
Epilepsy can develop at any age – from the very young to the very old. There tends to be a bimodal distribution of suffers – peaking in the youth and in the elderly. There are higher incidences of epilepsies in the younger population, often due to congenital and cryptogenic etiologies. There are higher incidences in the older population, often due to neoplastic and neurodegenerative etiologies. Epilepsy can develop at any age though – for a myriad of different reasons.
Epilepsy can be categorized into 2 different classes: the generalized epilepsies and the focal (partial) epilepsies. Generalized epilepsies can be further subdivided into the types of seizures that occur within them or epileptic encephalopathies (i.e. Lenox-Gastaut syndrome, Epileptic (Infantile) Spasms, Rett Syndrome, etc) and are classified as generalized because when seizures occur – on an EEG they appear to involve both hemispheres at the time of seizure onset. Focal (partial) epilepsies indicate epileptic disorders where seizures start in a part of the brain and may be localized there or spread to other regions of the brain or the whole brain. The focal epilepsies can be further subdivided into the region of the brain where seizures start: the frontal, parietal, occipital or temporal lobes. Temporal lobe epilepsy is the most common type of focal epilepsy and seizures within this region present bizarrely.
Realize that most seizures do not involve convulsive activity. Generalized tonic-clonic seizures, in fact, are the minority of seizures that most patients with focal epilepsy have and many non epileptology clinicians undertreat patients if they feel the patients are no longer having convulsive seizures. A culmination of nonconvulsive seizures however, can be very dangerous and increase the risk for SUDEP (sudden unexpected death in epilepsy) – where all epileptics are considered to be at a 1:10000 risk of SUDEP (some argue a 1:1000 risk). In addition, when patients do not have all seizures controlled – a vast majority may have progressive cognitive decline, changes in personality/mood, sleep disorders, etc.
Early recognition through a careful history, aggressive diagnostic testing and treatment involving medication, neuromodulation, dietary therapy and/or epilepsy surgery can ensure that a patient will not decline in the longterm. Unfortunately, due to the lack of proper screening and due to the misdiagnosis of many patients – there is a large cohort of people who never get diagnosed properly and therefore never get treated appropriately.
In attempting to keep this relevant (though I have so much to write about epilepsy), I will focus my discussion more on my general understanding out how chronic neurodegeneration brought forth by chronic neuroinflammation cause damage to then set forth the development of different types of epileptic syndromes. Regardless of the neurodegenerative neurological disorder (Alzheimer’s disease, Parkinson’s disease, certain epileptic disorders, Creutzfeldt-Jakob Disease), I believe in the theory that a common neuroinflammatory cascade can lead to different neurological disorders, depending on where and how the brain is attacked. The more data Anavex collects and the more varied neurological disorders 2-73 (and 3-71) seem to stabilize, the more I believe in the theory that there is a common pathophysiological mechanism to each diverse neurological disorder. 2-73 seems unique in that it is targeting a common pathophysiological process upstream (the events that cause damage) rather than targeting the structure that is already damaged by “repairing” it.
Think of the Golden Gate Bridge, a marvelous public work that is constantly exposed to the elements of the San Francisco Bay. It is a dynamic structure that, if left alone, will rust, become corrupted and eventually fail if it is not constantly maintained. Your brain and body are dynamic structures as well that need constant maintenance (provided at the cellular level) as long as cellular homeostasis is maintained. Just like how the Golden Gate Bridge can fail without proper maintenance, cells within the body brain can fail without proper maintenance. When there is a dissociation between the body’s/brain’s ability to repair itself amid the constant exposure to cellular stresses, degeneration occurs. It is only when the repair mechanisms are fixed that degeneration can be halted.
This is why 2-73 and 3-71 is unbelievable compared to prior medications that came before. This is on the precipice of a whole new class of neuro-biological therapies – targeting the pathophysiological – degenerative processes, not just targeting the regions already damaged. The body and brain are resilient and are capable of self-repair, if given the chance.
This is why I am so excited about Anavex – yes, it is early and yes, it is still speculation. But it is speculation steeped in already demonstrable data to show potential for efficacy in Alzheimers, Parkinsons, Infantile Spasms, Rhett Syndrome, chronic pain, etc. We have an understanding that when cellular mitochondria, the powerhouse of the cell, becomes dissociated from the cellular repair structure of the endoplasmic reticulum – pathology arises. We have also an understanding that if the mitochondria can reassociate with the endoplasmic reticulum, there can be a restart of the cellular repair structure – damaged cells (neurons) can heal themselves. Dead cells cannot.
Early diagnosis and recognition of neurodegenerative disorders will be of utmost importance when it comes to treatment of the myriad of neurological disorders 2-73 and 3-71 may be able to treat in the future. It is the role of clinicians like myself to get familiar with early recognition, to scratch more than just the surface and to see the forest amongst the trees especially when the eloquent generalized cortical network starts getting damaged (phenotypical changes in cognition, mood, emotional control, sleep occur). As the neurobiological therapeutics become better, so must the clinician prescribing these therapeutics. I am excited for my patients as Anavex continues to bring forth more data.
As Anavex reveals more pointed data, especially within the realm of the epileptic disorders, I will be more specific in describing each disorder (if time permits). I am confident about this company and its future – despite the fact that it is still a very early speculation. Science matters……that is all!
Good luck to all of the long Anavex investors.
