Page 7 Medical & Healthcare Expert Guide 2019
P. 7
7
At a time when scientific breakthrough and
discovery is leading to decreasing numbers of
those affected by many serious diseases and
illnesses, Alzheimer’s is the only leading cause
of death that is still on the rise. Why is this?
Because, as already mentioned above, we are living so much longer
and there is still no disease-modifying drug available that can arrest
the underlying cause of the disease.
Why exactly have previous efforts to find a
cure failed?
The basic pathology of the disease includes the production and
accumulation of Aß. Earlier therapeutic attempts by others at
lowering total Aß production were unsatisfactory as they directly
targeted the catalytic activities of ß- or -secretase, enzymes
γ
responsible for the cleavage of Aß from its precursor, the amyloid
precursor protein (APP). These enzymes also cleave as many as
60-90 other proteins besides APP, including Notch, many with
critical cellular functions, and inhibiting or modulating their
activities can produce many undesirable effects. Several - and
γ
ß-secretase inhibitors have been in clinical trials, although most
have now stopped development because of toxicity and off-target
effects. Thus while inhibiting or modulating the activities of these
enzymes successfully reduced Aß, they also inhibited as many as 60
other reactions in the cell, producing many detrimental off-target
effects. Another reason for their failure is they were administered
too late in the disease progression, when the damage to the
brain was already done. New therapeutic approaches that can
inhibit total Aß production early without targeting the activities
of the ß- or the -secretase are therefore urgently needed. Cenna’s
γ
technology does just that.
What is Cenna Bioscience doing differently?
Cenna’s approach is completely different and does not target the
secretases. Cenna’s candidate drugs are peptides derived from
Presenilin-1 which is part of the -secretase complex. Cenna’s
γ
compounds inhibit the production of Aß by specifically binding
APP at a different site from the ß- and -secretase cleavage sites
γ
and arresting its further processing to Aß (Dewji, N.N. et al (2015)
PLoS ONE 10(4): e0122451. doi:10.1371/journal.pone.0122451).
Importantly, these peptide-induced reductions of total Aß and Aß40
and 42 do not modify or inhibit either ß- or -secretase activities.
γ
Our lead candidate P8 inhibits the production of Aß in vitro, in a Tg
mouse model of AD and in patient-derived stem cells by over 50%,
is stable, and can be delivered to the brain.
New therapeutic
approaches that can inhibit
total Aß production early
without targeting the activities
of the ß- or the γ-secretase are
therefore urgently needed. Cenna’s
technology does just that.
At a time when scientific breakthrough and
discovery is leading to decreasing numbers of
those affected by many serious diseases and
illnesses, Alzheimer’s is the only leading cause
of death that is still on the rise. Why is this?
Because, as already mentioned above, we are living so much longer
and there is still no disease-modifying drug available that can arrest
the underlying cause of the disease.
Why exactly have previous efforts to find a
cure failed?
The basic pathology of the disease includes the production and
accumulation of Aß. Earlier therapeutic attempts by others at
lowering total Aß production were unsatisfactory as they directly
targeted the catalytic activities of ß- or -secretase, enzymes
γ
responsible for the cleavage of Aß from its precursor, the amyloid
precursor protein (APP). These enzymes also cleave as many as
60-90 other proteins besides APP, including Notch, many with
critical cellular functions, and inhibiting or modulating their
activities can produce many undesirable effects. Several - and
γ
ß-secretase inhibitors have been in clinical trials, although most
have now stopped development because of toxicity and off-target
effects. Thus while inhibiting or modulating the activities of these
enzymes successfully reduced Aß, they also inhibited as many as 60
other reactions in the cell, producing many detrimental off-target
effects. Another reason for their failure is they were administered
too late in the disease progression, when the damage to the
brain was already done. New therapeutic approaches that can
inhibit total Aß production early without targeting the activities
of the ß- or the -secretase are therefore urgently needed. Cenna’s
γ
technology does just that.
What is Cenna Bioscience doing differently?
Cenna’s approach is completely different and does not target the
secretases. Cenna’s candidate drugs are peptides derived from
Presenilin-1 which is part of the -secretase complex. Cenna’s
γ
compounds inhibit the production of Aß by specifically binding
APP at a different site from the ß- and -secretase cleavage sites
γ
and arresting its further processing to Aß (Dewji, N.N. et al (2015)
PLoS ONE 10(4): e0122451. doi:10.1371/journal.pone.0122451).
Importantly, these peptide-induced reductions of total Aß and Aß40
and 42 do not modify or inhibit either ß- or -secretase activities.
γ
Our lead candidate P8 inhibits the production of Aß in vitro, in a Tg
mouse model of AD and in patient-derived stem cells by over 50%,
is stable, and can be delivered to the brain.
New therapeutic
approaches that can inhibit
total Aß production early
without targeting the activities
of the ß- or the γ-secretase are
therefore urgently needed. Cenna’s
technology does just that.
