The two key areas are neuro inflammation and the process of...

The two key areas are neuro inflammation and the process of autophagy, the cell cleaning garbage disposal system.

I have re-listened to the presentation and as @SoT said its worth a second/third view. Its well to remind ourselves that approaching Alzheimer's, or any number of other neurodegenerative diseases like motor neuron disease, from the point of view of neuroinflammation or the loss of efficiency in/or the overpowering of autophagy is out-of-the-box thinking. I previously referred to Pharma relentlessly pursuing clumps of amyloid in Alzheimer's disease for little or no benefit. One could well ask the question why have all the Alzheimer's drugs failed? Its the scientific equivalence of insanity in testing the same target over and over again and expecting a different result.

Back to the critical thinking of our own scientific team at PYC. Sue Fletcher indicated that tackling the genetic cause of neurodegenerative diseases is difficult because disease is often undiagnosed until much later in life when symptoms emerge. By the stage that symptoms occur the degenerative processes are well underway and are usually evidenced by a build-up of misfolded proteins which can no longer be cleared by the garbage-disposal system. Further, its not the protein aggregates that kill the neuron cells but the neuroinflammatory response.

This is where it gets really exciting. The thinking is out-of-the-box and the disease hypothesis is soundly evidenced but developing drug candidates for neuroinflammation and the autophagy pathways is clearly challenging. Listening to the presentation one is reminded, however, that PMOs are stable molecules with an outstanding safety profile and PPMOs can possibly go into regions deep within the brain where cargos are required in the intracellular space.