Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Feb;182(3):510-529.
doi: 10.1111/bph.17353. Epub 2024 Oct 8.

Beneficial effects of CHF6467, a modified human nerve growth factor, in experimental neonatal hypoxic-ischaemic encephalopathy

Elisa Landucci  1 , Dalila Mango  2   3 , Silvia Carloni  4 , Costanza Mazzantini  1 , Domenico E Pellegrini-Giampietro  1 , Amira Saidi  2 , Walter Balduini  4 , Elisa Schiavi  5 , Laura Tigli  5 , Barbara Pioselli  5 , Bruno P Imbimbo  5 , Fabrizio Facchinetti  5
Affiliations

Beneficial effects of CHF6467, a modified human nerve growth factor, in experimental neonatal hypoxic-ischaemic encephalopathy

Elisa Landucci et al. Br J Pharmacol. 2025 Feb.

Abstract

Background and purpose: Therapeutic hypothermia (TH) has become the standard care to reduce morbidity and mortality in neonates affected by moderate-to-severe hypoxic-ischaemic encephalopathy (HIE). Despite the use of TH for HIE, the incidence of mortality and disabilities remains high.

Experimental approach: Nerve growth factor (NGF) is a potent neurotrophin, but clinical use is limited by its pain eliciting effects. CHF6467 is a recombinant modified form of human NGF devoid of algogenic activity (painless NGF).

Key results: In rodent hippocampal slices exposed to oxygen and glucose deprivation, CHF6467 protected neurons from death and reverted neurotransmission impairment when combined with hypothermia. In a model of rat neonatal HIE, intranasal CHF6467 (20 μg kg-1) significantly reduced brain infarct volume versus vehicle when delivered 10 min or 3 h after the insult. CHF6467 (20 and 40 μg kg-1, i.n.), significantly decreased brain infarct volume to a similar extent to TH and when combined, showed a synergistic neuroprotective effect. CHF6467 (20 μg kg-1, i.n.) per se and in combination with hypothermia reversed locomotor coordination impairment (Rotarod test) and memory deficits (Y-maze and novel object recognition test) in the neonatal HIE rat model. Intranasal administration of CHF6467 resulted in meaningful concentrations in the brain, blunted HIE-induced mRNA elevation of brain neuroinflammatory markers and, when combined to TH, significantly counteracted the increase in plasma levels of neurofilament light chain, a peripheral marker of neuroaxonal damage.

Conclusion and implications: CHF6467 administered intranasally is a promising therapy, in combination with TH, for the treatment of HIE.

Keywords: hypothermia; neonatal brain damage; neuroinflammation; neuroprotection; painless mutant human nerve growth factor.

PubMed Disclaimer

References

REFERENCES

    1. Alexander, S. P. H., Fabbro, D., Kelly, E., Mathie, A. A., Peters, J. A., Veale, E. L., Armstrong, J. F., Faccenda, E., Harding, S. D., Davies, J. A., Beuve, A., Brouckaert, P., Bryant, C., Burnett, J. C., Farndale, R. W., Friebe, A., Garthwaite, J., Hobbs, A. J., Jarvis, G. E., … Waldman, S. A. (2023). The Concise Guide to PHARMACOLOGY 2023/24: Catalytic receptors. British Journal of Pharmacology, 180, S241–S288. https://doi.org/10.1111/bph.16180
    1. Apfel, S. C., Kessler, J. A., Adornato, B. T., Litchy, W. J., Sanders, C., & Rask, C. A. (1998). Recombinant human nerve growth factor in the treatment of diabetic polyneuropathy. NGF study group. Neurology, 51, 695–702. https://doi.org/10.1212/WNL.51.3.695
    1. Armogida, M., Spalloni, A., Amantea, D., Nutini, M., Petrelli, F., Longone, P., Bagetta, G., Nisticò, R., & Mercuri, N. B. (2011). The protective role of catalase against cerebral ischemia in vitro and in vivo. International Journal of Immunopathology and Pharmacology, 24, 735–747. https://doi.org/10.1177/039463201102400320
    1. Brust, V., Schindler, P. M., & Lewejohann, L. (2015). Lifetime development of behavioural phenotype in the house mouse (Mus musculus). Frontiers in Zoology, 12, S17. https://doi.org/10.1186/1742-9994-12-S1-S17
    1. Capsoni, S., Covaceuszach, S., Marinelli, S., Ceci, M., Bernardo, A., Minghetti, L., Ugolini, G., Pavone, F., & Cattaneo, A. (2011). Taking pain out of NGF: A “painless” NGF mutant, linked to hereditary sensory autonomic neuropathy type V, with full neurotrophic activity. PLoS ONE, 6, e17321. https://doi.org/10.1371/journal.pone.0017321

MeSH terms

LinkOut - more resources