THERAPEUTIC FOCUS

Post-Traumatic Stress Disorder

Post-Traumatic Stress Disorder is a serious chronic and debilitating psychiatric disorder that can occur in people who have experienced or witnessed a life-threatening event, such as a natural disaster, serious accident, terrorist incident, sudden death of a loved one; war; or rape or other violent personal assault. It is characterized by a re-experiencing of the traumatic event through intrusive flashbacks and nightmares, sleeping troubles, avoidance behaviors, hyper-arousal, irritation and anger.

PTSD scale

Chronic PTSD has dramatic consequences on private and professional life, impacting quality of life and social interactions, and is associated with significant comorbidities like major depression, substance and alcohol abuse, panic disorder; medical comorbidity, reduced life expectancy; disability in daily activities, as well as mortality due to suicide often being the ultimate solution for sufferers. Considering the relative ineffectiveness of current pharmacotherapy for PTSD, it is vital to develop more effective treatment strategies and new modes of action, for traumatized people.

PTSD stats

PTSD is increasingly recognized as both a disorder of enormous mental health and social burden, but also as an anxiety disorder that can be defined as a disorder of fear and stress dysregulation. The neural circuitry underlying these pathways in both animals and humans are becoming increasingly well understood.
It has been observed in PTSD patients, that specific areas of the brain playing a crucial role in the detection of threat, fear learning, fear expression (amygdala), memory of emotional events or encoding for episodic memories (hippocampus), are dysfunctionning. In particular it was emphasized the importance of the role of glutamate in these regions, in the production of the traumatic memory, as well as the emotional components of PTSD
Primary targets of novel therapeutic agents for PTSD are compounds that can stabilize glutamate levels without interfering with the essential role of glutamate in learning and memory.

Some references:
Kessler RC et al. (1995) Posttraumatic stress disorder in the National Comorbidity Survey. Arch Gen Psychiatry, 52(12):1048.
Institute of Medicine. Treatment for Posttraumatic Stress Disorder in Military and Veteran Populations: Final Assessment. Washington, DC: The National Academies Press, 2014. doi:10.17226/18724.
Olesena J et al. (2012) The economic cost of brain disorders in Europe. European Journal of Neurology, 19:155.
Burri A et al. (2014) Differences in prevalence rates of PTSD in various European countries explained by war exposure, BMC Research Notes, 7:407.
Ralevski E, et al. (2014) PTSD and comorbid AUD: a review of pharmacological and alternative treatment options. Substance Abuse and Rehabilitation, 5:25.
Norman SB et al. (2012) Review of Biological Mechanisms and Pharmacological Treatments of Comorbid PTSD and Substance Use Disorder. Neuropharmacology, 62(2): 542.
Nishi D et al. (2015) Glutamatergic system abnormalities in posttraumatic stress disorder. Psychopharmacology (Berl), 232(23):4261.

 

Hearing Loss

Hearing loss is by far the most prevalent inner ear disorder; the World Health Organization estimates that 500 million people worldwide have mild to moderate to severe hearing loss.

Hearing loss may develop slowly over many years or set in acutely, e.g. following some noise or head trauma. It may be either due to insufficient sound conduction from the outer to the inner ear or much more frequently to damage to the hair cells and neurons in the cochlea or to the auditory nerve (also called “sensorineural hearing loss”).

The challenges of preventing or treating hearing loss, including noise-induced hearing loss (NIHL), sensorineural hearing loss (SNHL) and age-related hearing loss (ARHL, presbycusis), share similarities with other highly prevalent chronic medical conditions, such as stress-related disorders (PTSD), or neurodegenerative diseases, costing billions of euros annually.

More importantly, hearing loss and tinnitus are listed as the top 2 service connected disabilities for all veterans, followed by PTSD, particularly prevalent in servicemen and women returning from Iraq and Afghanistan (Source: American Tinnitus Association).

In addition, hearing loss is a very common occupational or recreational medical outcome for teenagers, leading progressively to major hearing impairment.

Lastly, presbycusis affects up to half of people over the age of 65, and the onset of hearing loss can occur before this age. It is set to become an increasing problem, either caused by genetics or environmental stressors, which can contribute significantly to the causation of social isolation, dementia and depression. NIHL makes up 9% of all types of hearing loss in the developed world. NIHL is the second most common form of permanent hearing loss, and can also be a major contributing factor to presbycusis.

Hearing loss may have serious impacts on professional and personal lives, e.g. through reduced job performance and earning power, impaired memory and ability to learn new tasks or reduced alertness and increased risk to personal safety.

While new investigational drugs are progressing through human clinical testing, there are no single EMEA nor FDA-approved therapeutic treatments for NIHL, ARHL or tinnitus, which urgently warrant novel interventions.