ChasRiver_Aug2022_Perspectives-Toward-a-Treatment - 5

PERSPECTIVES
Many of us with elderly relatives have been affected
indirectly by AD, but you can imagine a young parent, a
sibling, or a close friend in the prime of life, in their 30s
or 40s, raising a family, building a career, and all of a
sudden getting a diagnosis that says they're going to start
to suffer from dementia and gradually become incapacitated
before they've fully lived their adult life. That's
really what we're up against. When we think about the
patients and our ability to do something to help them-
that's our driver and mission.
Anjali Sarkar: Drug development for
neurodegenerative diseases, particularly AD,
has met with little success over the past few
decades. What are the reasons behind the lack
of drugs for AD and what convinces you that
Paros Bio can make a difference in this space?
ERIC SCHAEFFER:
Generally, drug development has a greater chance of success
when the underlying disease mechanism is understood.
Sometimes people get lucky. Luck is great, but it's not a
strategy. If you want to go after a disease effectively, you
must understand the biology behind it. There have been
many hypotheses about the underlying causes of AD and
that's led to many treatment approaches, most of which
probably aren't directed towards the underlying cause.
The other issue has been that late-onset AD is not a
single disease. While AD is defined by a well-described
pathology-the plaques and tangles that are found in
the brains of these patients-there are likely to be many
different mechanisms that ultimately converge on this
common pathology.
The distinction between sporadic AD and ADAD, the
genetic form we are working on at Paros, is that the latter
is unequivocally caused by specific mutations in a known
gene. So, in terms of the underlying disease etiology, we're
working on a much more homogeneous form of the disease.
We're also working on mutations in genes with wellunderstood
functions. We're going after a disease where
we understand the genetics and the consequences of the
mutations that cause it. Therefore, conceptually, trying to
correct those mutations through gene therapy is a logical
approach, which we think is different than what has been
tried up until now, which is a broad approach to try to treat
AD with one therapy when the disease probably has many
underlying causes.
HOLDEN JANSSENS:
AD is such a devastating disease, so profound across our
whole culture, and there are so many people affected by
it that even though there have been failures, there is going
to be continued activity in this space. That's the business
case for it. Also, we've all been touched by someone that
has experienced some form of dementia, and there's going
to be a continued push to come up with some solution to
alleviate symptoms or to slow down the disease. Because
it's such a devastating and relatively common disease in
our world, while there've been several recent failures, you
don't see that decreasing the effort to develop new ways of
targeting the disease.
Anjali Sarkar: ADAD, the subset of AD that
you are going after, is a rare form of the disease.
What led Paros Bio to take on ADAD first?
ERIC SCHAEFFER:
As mentioned, ADAD offers the opportunity to go after
a well-understood genetic form of AD. Also, one of the
challenges in developing effective treatments for AD or for
any chronic neurodegenerative disease, is that the longer
the disease progresses, the harder it is to have an effective
therapy because you're losing brain cells every day. When
someone first manifests symptoms, they've had the disease
for a long time. One of the exciting possibilities when you're
treating a disease that has a genetic cause is that you can
identify patients with 100% certainty, early in the disease
and prior to symptom onset. These are patients who have
the mutation from birth. While I don't think we're going
to start treating children, this opens the door to treating
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ChasRiver_Aug2022_Perspectives-Toward-a-Treatment

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