This IP covers: (a) the broad use of FGF21-based drugs used in conjunction with temperature management in neonates for the treatment of brain injury, and (b) the unique effect of FGF21 drugs to augment the levels of beneficial cold shock proteins in neurons.
Description
The incidence of birth asphyxia is ~1–4 per 1,000 live births each year in the United States. Market analysis suggests that the cost of treating birth asphyxia globally is increasing and could reach ~$2 billion/yr by 2030. Therapeutic hypothermia (TH) is the standard of care to treat newborns with hypoxic-ischemic (HI) brain injury but is ineffective in 6 out of 7 patients. Thus, drugs that enhance the efficacy of cooling (TH- adjuvants) are desperately needed to improve outcomes in brain injured populations. Fibroblast growth factor 21 (FGF21) is a remarkably safe neuroprotective hormone. Numerous clinically tested FGF21 analogs have been developed and are well-tolerated in humans. They include compounds like LY2405319, PF-05231023, Pegbelfermin, Pegozafermin, Efruxifermin, and BOS-580. And there are many others in various stages of preclinical development. University of Pittsburgh researchers discovered that FGF21 therapies show great promise for enhancing neuroprotection and to improve neurologic outcomes in temperature managed neonates with ischemic brain injury. There are many ways in which FGF21 supplementation may improve neuroprotective cooling by targeting a variety of physiological mechanisms. One novel pathway under investigation, also related to this IP, is that FGF21 treatment promotes the induction of neuroprotective cold shock proteins at a range of body temperatures.
Applications
• To induce neuroprotection in pediatric patients with ischemic brain injury.
• To enhance the efficacy of targeted temperature management (TTM).
• To enhance the efficacy of therapeutic hypothermia (TH).
• To increase the expression of neuroprotective molecular cold shock proteins in neurons.
Advantages
1. FGF21 has a short half-life. This makes it ideal for use in the intensive care unit (ICU) where drugs need to be able to be rapidly titratable. 2. There are many different FGF21 analogs that are under clinical development by major pharmaceutical companies. This IP offers broad coverage for the use of any FGF21-based therapy (i.e. method) to induce neuroprotection in a neonate with ischemic brain injury (see independent claim). 3. During subsequent years after our initial submission for patent protection, numerous preclinical studies from many different independent groups published extensive data that further supports the use of FGF21 therapies for the treatment of developmental brain injury. 4. Contemporary neonatal-ICU care teams are actively searching for novel TH-adjuvants, and FGF21 drugs can easily be translated into the clinic for that purpose.
IP Status
https://patents.google.com/patent/US20230364189A1
