The development of neurotherapeutics is the next frontier in biomedical science.
The brain determines how we think, what we do, who we are. As we age, changes to our brain inevitably occur, including death of neurons, loss of synapses, brain shrinkage and cognitive impairment. In the most extreme cases, cognitive impairment is due to neurodegenerative processes, including those seen in Alzheimer's disease and other dementias. Cerecin is committed to the maintenance of brain function in health and disease.
Alzheimer's disease (AD) is an age-associated, neurodegenerative disease characterized by a progressive decline in memory and language, and, pathologically, by accumulation of senile plaques and neurofibrillary tangles in the brain. Despite significant advances in AD research, there exists a tremendous need for new AD therapies. Most developed countries will experience a dramatic demographic shift toward an older population in the next 50 years, which is anticipated to greatly increase the prevalence of AD. The rise in the number of AD patients will place a tremendous social and economic burden on the developed world.
Despite being identified over 100 years ago, the cause of Alzheimer's disease is still not well understood. Unfortunately, drug development for AD has proven to be very difficult, with few successes and many failures. Currently, only 5 drugs are approved for the treatment of AD including 4 cholinesterase inhibitors (tacrine, donepezil, rivastigmine, galantamine) and an N-methyl-D-aspartate (NMDA) receptor antagonist (memantine). No new compounds have been approved for AD since 2003. Many failures in AD drug development have occurred, with both small molecules and immunotherapies failing to show significant effects or having unacceptable toxicity. As a result, there is a tremendous need for innovative AD therapies.
The lack of new treatments and the repeated failure of pipeline drugs have significantly impacted not only the lives of patients and associated family members, but also the economies of many developed and emerging countries. In 2013, it was calculated that the total cost for dementia care (largely AD) in the US was $215 billion. Further calculations demonstrated that the increasing prevalence of dementia, due to the aging of the US population will result in an increase of nearly 80% in total societal costs by 2040, with total care costs of approximately $511 billion. Therefore, the development of new treatments that delay onset or progression of the disease is desperately needed1. As the number of elderly surges in Asia, so does the prevalence of AD. Globally, the number of people with dementia is expected to increase to 135 million in 2050 with almost half of these cases coming from the Asia Pacific region2.
Infantile Spasms (IS), also known as West Syndrome, is a form of epilepsy that occurs in infants. Infantile Spasms is a complex, rare and devastating disorder which can lead to severe consequences if not treated early. IS may occur as the result of another condition (symptomatic IS), such as infections of the brain, oxygen deficiency in the womb, metabolic and immunologic disorders, or there may be no identified etiology (cryptogenic IS). The majority of infants with IS present before the age of 1 year.
The clinical features include spasms which may involve the whole body, and which may be flexor or extensor. Some spasms are very subtle and resemble head nods. Spasms tend to occur in clusters and may be very numerous over the course of the day. In addition to the typical spasms, significant EEG abnormalities, including a very disorganized rhythm known as hypsarrhythmia, are seen. Developmental delay completes the usual triad of features. The spasms themselves may cease by the age of 4, however some patients go on to develop other seizure disorders and many are left with learning disabilities. If treatment begins early, ideally within 1 month of symptoms, prognosis for children with the disorder can be more positive.
Gold standard treatments for Infantile Spasms are adrenocorticotrophic hormone (ACTH), corticosteroids (e.g. prednisolone), or vigabatrin (VGB)3. Current treatments are associated with serious side effects and there are a substantial proportion of cases in which there is recurrence despite initial remission with treatment.
There is an urgent, unmet need for additional safe and effective drug treatments that can be well tolerated in infants and young children, and that don’t require the same level of monitoring and laboratory assessments as currently approved treatments.
There are no FDA approved ketogenic interventions or treatments for IS. Cerecin has developed an investigational compound called tricaprilin, which has been shown to elevate plasma ketone levels and reduce spasms in a rat model of infantile spasms. Tricaprilin is currently in clinical development to investigate the safety, tolerability, and efficacy of daily administration of tricaprilin in infants with this devastating condition.
The safety and efficacy of tricaprilin have not been established
Migraine is the third most common disease in the world, affecting 1 billion people worldwide. There is no cure for this neurologic disorder, characterised by attacks of moderate to severe throbbing head pain. In some cases, the so-called migraine with aura, the headaches may be accompanied by sensory disturbances, such as blurred vision, flashes of light, or blind spots. Migraine can affect anyone, but is most likely to occur in people who have family history of migraine and is most common in women between the ages of 18-44.4
Science has yet to fully understand the causes of migraine, but research points towards chemical compounds and hormones such as serotonin and estrogen playing a role in the severity of migraine pain. Migraine places a huge economic burden on societies through lost productivity, sick days and higher healthcare costs. In the US alone, more than 157 million workdays are lost due to migraine.5
Currently prescribed preventative medications for migraine include amitriptyline and other tricyclic antidepressants, propranolol and other beta-blockers, calcium channel blockers, topiramate and other anti-epileptic agents, and the new class of drugs, known as Calcitonin Gene Related Peptide (GCRP) antagonists.6
Currently prescribed treatments for acute migraine attacks include acetaminophen, nonsteroidal anti- inflammatory drugs (NSAIDs), triptans, NSAID-triptan combinations, dihydroergotamine, non-opioid combination analgesics, and several anti-emetics, as well as some CGRP antagonists.
Despite increased understanding of migraine and recently approved novel therapies for people with migraine, there remains a need for the development of additional drug treatments.
Ketogenic diets (KD) have been reported to reduce migraine frequency. Tricaprilin is an investigational agent that has been shown to induce ketosis and is currently being investigated for the preventative treatment of migraine.
The safety and efficacy of tricaprilin have not been established.