Traumatic Brain Injury
One of BHR’s lead products is intravenous progesterone as a neuroprotective agent in severe traumatic brain injury (TBI). This project does not employ our EHG® platform, using instead another parenteral route of administration (i.v.). It also leverages our institutional experience with, and commercial position in, progesterone. Besins was the first to develop and commercialize an oral formulation of progesterone and is today one of the world’s largest consumers of progesterone as an active pharmaceutical ingredient.
TBI is a non-degenerative, non-congenital insult to the brain from an external mechanical force.1 Incidence of TBI in all industrialized countries is comparable to the US, with estimates ranging from 150 to more than 300 per 100,000.2 There are approximately 66,000 deaths annually attributed to TBI in Europe.3
"Traumatic brain injury is the leading cause of death and disability in children and young adults worldwide and is involved in nearly half of all trauma deaths."4
The leading cause of TBI in the world is road traffic accidents5; approximately 3000 people die and 30,000 people are injured daily in traffic accidents.6 As safety precautions increase in the industrialized world, mortality from road traffic accidents has declined, but the problem is increasing in developing countries.7 This epidemic of traffic accidents in developing countries is accentuated by high mortality rates:
Country/Region8 |
TBI Mortality Rate/ |
Europe |
15 |
Scandinavia |
10 |
India |
20 |
United States |
30 |
China, Province of Taiwan |
38 |
South Africa |
81 |
Colombia |
120 |
While no pharmacological agent has yet been proved to be effective in improving TBI outcomes9 progesterone has been shown to enhance survival and functional outcomes in human TBI patients.10 Progesterone exerts a variety of effects that may be responsible for these observations:
- Reducing both vasogenic and cytotoxic edema
- Reducing lipid peroxidation by a variety of mechanisms
- Controlling inflammation by reducing cytokine release and inhibiting immune cell activation and migration
- Reducing neuronal apoptosis
- Upregulating GABA-A, which decreases release of glutamate and other excitatory neurotransmitters
- Inducing remyelinization11
BHR has exclusively licensed the rights to a patent family claiming the use of progesterone to treat traumatic brain injury, along with preclinical and clinical data from a Phase 2 study that showed a mortality benefit in TBI patients.12 BHR intends to initiate a Phase 3 global multi-center pivotal trial of i.v. progesterone infusion in severe TBI patients in late 2009, with the collaboration of the American Brain Injury Consortium (ABIC) and the European Brain Injury Consortium (EBIC).
1 Traumatic Brain Injury in the United States: A Report to Congress (1999)
2 Traumatic Brain Injury: Methods for Clinical and Forensic Neuropsychiatric Assessment, p.2, Granacher, ed. (CRC Press 2003).
3 Socin et al. JAMA 273:22 (1995)
4 Neurological Disorders: Public Health Challenges, p. 164 (World Health Organization 2006).
5 Id. at 168.
6 Id.
7 Id.
8 Id. at 166.
9 Wright et al., Annals of Emer. Med. 49: 391-402 (2007).
10 Wright et al, (2007) supra.; Xiao et al., Critical Care 12:R61 (2008).
11 Stein, (2007) supra,
12 See Wright et al, (2007) supra.