New peptides to treat cognitive impairment of age-related diseases

Novel Folate Receptor alpha (FRα) binding peptides induce brain cell reprograming and rejuvenation, enhancing cognitive function in aged mice. These unique peptides are able cross the blood-brain barrier and specifically bind to neuroepithelial FRα.

Market need: Age-related diseases affecting neuronal functions are on the rise due to an aging population, affecting millions of people above the age of 65. Decreased folate levels have been related to aging, with around 30% prevalence of folate deficiency in the elderly. Indeed, folate deficiency is linked to higher dementia risk and increased mortality. Human family of folate receptors include folate receptors (FR) α, β, and γ, playing a critical role in several biological process. Although folate supplement is used as treatment to reduce memory impairment in the elderly, its benefits are limited due to toxic side effects associated with high uptake, as it binds and activates all FR family members.

Proposed solution: These novel FRα-binding peptides are able to cross the blood brain barrier and specifically bind to neuroepithelial FR-a inducing its translocation into the nucleus and activation as transcription factor. Pre-clinical in vitro and in vivo studies showed that administration of these peptides leads to enhanced expression of Yamanaka factors Sox2 and Klf4, as well as increased protein levels of PSD95 in cortical neurons, and reduced density of perineuronal nets in the hippocampus and somatosensory neocortex. This molecular modifications were related to notable improvement in new object recognition memory, particularly in the long term but also in short-term spatial memory in aged mice.

Competitive advantages

Cognitive improvement of recognition and spatial memory.
Specific binding to neuroepithelial FRα, preventing from systemic toxic effect associated to high-doses of folate administration.
Blood-brain barrier permeability, enabling versatile administration routes, including intracranial, peritoneal and intragastric.
Safety and efficacy proven in pre-clinical mouse models.