“When the steroid sulfatase gene is deleted in worms, the ability to remove sulfate from sulfated steroids is lost and the level of this molecule increases. This generates some surprising effects: nematodes with Alzheimer’s features reduce their symptoms and those without Alzheimer’s are long-lived”
“When the steroid sulfatase gene is deleted in worms, the ability to remove sulfate from sulfated steroids is lost and the level of this molecule increases. This generates some surprising effects: nematodes with Alzheimer’s features reduce their symptoms and those without Alzheimer’s are long-lived”
Prof. Manuel Muñoz
Science
Steroid hormones on aging
Steroid hormones are involved in different physiological processes, including sexual maturation, metabolism regulation and inflammation. For a long time, they have been in the spotlight of studies on aging and neurodegeneration diseases.
The classical function of steroid hormones is the activation of hormones receptors to transcribe their target genes. These steroid hormones can be sulfated and desulfated by:
- A sulfotransferase enzyme, which adds a sulfate group, generating a change in the chemical characteristics of the hormone and impairing its function as a hormone receptor activator.
- A sulfatase enzyme, which removes a sulfate group from them.
Neurosteroids: neurotransmission regulators
In the central nervous system, steroid hormones have been described as modulators of neuroreceptors by direct physical interaction. In fact, the sulfated species can affect neuroreceptors differently to the non-sulfated form. Both versions acting in brain are defined as neurosteroids and the key enzymes that modify their concentration (sulfotransferases and sulfatases) are neurotransmission regulators. Several pieces of evidence suggest that the sulfated form of these steroid hormones is neuroprotective.
ONESTX-1: inhibitor of the steroid sulfatase enzyme
Our pipeline contains products able to increase the sulfated form of neurosteroids. Our leading candidate is the sulfatase inhibitor ONESTX-1 that increases a pool of sulfated steroid hormones and sulfated neurosteroids.
The effect of the increment of sulfated neurosteroids promotes a cognitive improvement in animal models, better memory skills and decrease of protein deposits in brain.
These results are available in a recent publication in Nature Communications by the founding team and have strong intellectual property protection through granted and pending patents.
The main component of ONESTX-1 has been used with other indications safely in humans and its chemical properties could be successfully applied to neurodegenerative disease regarding our results.
