CSIC has patented a series of new glutamic acid derivatives that show several pharmacological activities in a single small molecule, particularly in a potential treatment of the Alzheimer’s disease.

The present technology describes the biological multiactivity showed by a series of new compounds. In these compounds, the glutamic acid chain acts as a linker of three pharmacophoric groups with different pharmacological activities. They could be very useful as the base of a treatment of neurodegenerative processes such as the Alzheimer's disease (AD).

AD is a neurodegenerative process associated with ageing. Its initial cause still remains unclear but there is increasing evidence they are very close to failures in the modulation of the neuronal oxidative processes. The metabolism of the brain generates a high amount of toxic free radicals, but the neurons are provided with their own defence mechanism in order to eliminate these radicals. This antioxidant system fails in AD conditions, the concentration of the free radicals increases and, as a consequence, this oxidative stress induces the rest of the processes associated to AD, starting with changes in the conformation and subsequent aggregation of the amyloid protein, the other process associated to the beginning of AD. It is followed, years later, for an impairment of the cholinergic neurotransmission with its well-known dramatic symptoms and, finally, massive neuronal loss and death.

As a resume, the AD is the consequence of several associated aberrant processes, where the oxidative stress and aggregation of the amyloid protein look to play a crucial role as the initial source of the following failures. So, it would be highly desirable to have a single molecule with neuroprotective and antioxidant activities, capable of inhibit the conformational changes and aggregation of the amyloid protein and to restore or, at least, enhance the cholinergic neurotransmission in order to slow the symptoms and even stop the disease.

The new and small glutamic acid derivatives described in the patent have all these biological activities, as demonstrated through in vitro cellular studies. They also are able to cross the blood-brain barrier, an essential quality for any drug to act in the central nervous system. All these features made them very attractive compounds for a treatment of the AD.

 

Priority patent application filed

Technical cooperation; R&D collaboration; commercial agreement with technical assistance; license agreement.