This technology describes caspase-2 inhibitors for the treatment of neurodegenerative diseases such as Alzheimer’s disease.
Unmet Need: Disease-modifying therapies for neurodegenerative disorders
Though neurodegenerative disorders are highly prevalent in aging populations, there are currently few treatment options available. A majority of these treatments focus on delaying disease onset and managing disease symptoms rather than addressing the biological causes of neurodegeneration. There is a significant unmet need for therapies that combat the underlying causes of neurogenerative diseases and their associated cognitive decline.
The Technology: Non-invasive caspase-2 inhibitors for the treatment of neurodegenerative diseases
This technology describes a group of peptidomimetics that can inhibit the activity of caspase-2, a protease associated with neurodegenerative disorders such as Alzheimer’s disease. This technology preferentially blocks the active site of caspase-2 compared to other caspases and related proteases. It can be delivered non-invasively and has been shown to prevent synapse loss caused by amyloid beta oligomers in primary neurons.
This technology has been tested in vivo in primary cultured neurons, in human neurons, and in a sporadic mouse model where amyloid beta oligomers are directly injected into the brain.
Applications:
- Treatment for neurodegenerative disorders including Alzheimer’s disease and frontotemporal dementia
- Prevention of cognitive decline
- Neuroprotective treatment
- Tool to study the regulation of pathogenic proteins in the brain
Advantages:
- Prevents synapse loss and neuronal cell death
- Delivered non-invasively
- Treats several neurodegenerative disease pathologies
- Selective inhibition of caspase-2
Lead Inventor:
Carol M. Troy, M.D./Ph.D.
Related Publications:
Bosc E, Anastasie J, Soualmia F, Coric P, Kim JY, Wang LQ, Lacin G, Zhao K, Patel R, Duplus E, Tixador P, Sproul AA, Brugg B, Reboud-Ravaux M, Troy CM, Shelanski ML, Bouaziz S, Karin M, El Amri C, Jacotot ED. “Genuine selective caspase-2 inhibition with new irreversible small peptidomimetics” Cell Death Dis. 2022 Nov; 13(11): 959.
Akpan N, Serrano-Saiz E, Zacharia BE, Otten ML, Ducruet AF, Snipas SJ, Liu W, Velloza J, Cohen G, Sosunov SA, Frey WH, 2nd, Salvesen GS, Connolly ES, Jr., Troy CM. “Intranasal delivery of caspase-9 inhibitor reduces caspase-6-dependent axon/neuron loss and improves neurological function after stroke” The Journal of Neuroscience : the official journal of the Society for Neuroscience. 2011 Jun; 31(24): 8894-904.
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