(Thank
you, Laura Mitic and the Bluefield Project for all you do and providing
feedback so we can share with the world the great things you are doing).
Post overview. -
- Analogy to add perspective to what frontotemporal dementia (FTD) is
- Summary of what your previous donations have gone towards and the benefits so far
- Details and explanation of hope for a cure/prevention
1. FTD Perspective
To the audience:
If this were in person, I would ask you to close your
eyes as I take you on a journey.
In lieu, I’ll simply ask you to read on with an open heart:
I'd like you to imagine yourself being relocated to a remote
Chinese village. Somewhere where you do
not speak the language nor can you read or understand it. You've been sent there alone, and not by choice.
Now imagine, you've been told you will be there for the remaining days of your life.
At first it would be a struggle, but you, think, "I'll be resourceful and adapt: body language, photos, and just plain pointing goes a long way."
Now imagine, despite immersion into the culture and language,
your comprehension declines the longer you are there instead of improving.
You look at a menu or any written instruction and it becomes
more and more foreign to you every day.
Your intelligence is still intact. You are aware of what is happening. But you are alone in this foreign village
where you cannot grasp what people are saying, you cannot read the written
language, you cannot write it; even if you are looking right at it, your brain cannot
tell your hand how to replicate it. Before you know it, your writing is that of a child's.
The world is hustling and bustling around you, but you can’t
keep up.
Your ability to speak, slowly, deteriorates as well; until after
a few years in the village, you have lost your voice altogether.
And then, comes the physical decline. Incontinence, walking and balance declines,
muscles stiffen as they begin to atrophy.
Eating, now a challenge; swallowing is no longer instinctual….
In 2008, my mom, at the age of 56 was sent to a foreign
village. My grandmother quickly
followed.
That village is called frontemporal dementia (FTD). For some, no one knows why they get sent
there. In my family's case, we have one
of the familial forms of FTD, the genetic mutation-- FTD-GRN.
In a nutshell, “FTD-GRN is a rare, early-onset and rapidly
progressive neurodegenerative brain disorder that can affect behavior,
cognition, language and motor skills, due to a reduction in the progranulin
protein”...it is fatal. (FORUM Pharmaceuticals
Press release, Oct 2014). For anyone in
the family that was passed the gene, now live with the 50% risk of passing it
on to our children.
Three years ago, on March 13, 2013, after five years of FTD
entrapment, Mom took her final breath and let go. She was only 61. She lives on through her
husband of 35 years, 5 children and a growing number of grandchildren (almost
7!)
For the past three years, all of you have helped raise over $15k, in memory of my mom,
Mary Hall.
All proceeds have gone to the Bluefieldproject based out of
UCSF (and collaborates with other researchers across the U.S., Canada and
Europe).
But what
has been the benefit to your donations to date?
Below explains what your generosity has impacted.
But
first and foremost:
~~~~Thank you~~~~~
~~~~~~~~~~~~~~~~You have made
all the difference~~~~~~~~~~~~~~~
The skinny:
Because of all of you, there is progress and hope. Your donations accelerated the preliminary
research which secured a larger grant for clinical trials!! On people, not rats. Real clinical trials! I
repeat: Clinical trials for FTD with GRN Mutation, have been funded!!!
Read on to learn more on:
- Details on how the trial came to be
- What the trial will entail
- Details on how you find out about other clinical trials occurring and more info FTD in general.
While we still have a long way to go, thanks to all of you,
we are on our way. If there is any
silver lining to having a genetic mutation that causes dementia in the prime of
one's life, rapidly declines and is deemed fatal ... FTD-GRN is the "low
hanging fruit" and your donations have given my family and the other 100s
of thousands caregivers and affected TANGIBLE HOPE. We still have a long road ahead of us. Trials can take years, if not decades. But this is a huge step in the right direction
Mom would be proud and humbled, as we are as well.
With Love,
~The Hall Family~
 |
| 2007 - Just a year before diagnosis, Mom, Dad and Heidi celebrate Tina graduating. |
The Details:
As we all know, the research and medical world is not
cheap. On a shoestring budget, devoted
doctors (Howie Rosen, MD at UCSF and Brad Boeve at Mayo Rochester) have been
collecting research data, mostly in the evenings and weekends, for 10-15 years.
Drs. Rosen and Boeve have collected research data on several
hundred subjects (patients and unaffected relatives participating in research
programs) from families with known FTD mutations. These research data included extensive clinical assessments, structural
and functional brain imaging, and blood and CSF samples. In many cases,
these data were collected prospectively, before we knew gene mutations caused
FTD, with the expectation that they could be used in exploratory studies. As
our understanding of the genetics of FTD increased and patients were genotyped,
this became possible. Drs Rosen and Boeve
aimed to mine these data to better understand changes that occur with familial
FTD over time - and indeed they were doing so, on a shoestring budget, at night
and on the weekends, but it was slow going.
They needed help organizing and parsing their data.
Your
donations went to support two research assistants (one at each center) to
collate and analyze the data, thereby accelerating the completion of the
analysis. Their completed analyses were included in an
NIH grant application that proposed studying changes in familial FTD
patients over time with additional (in some cases, newer) techniques. This kind
of longitudinal study is key for estimating rates of change across clinical
stages. In turn, knowing rates of change
across clinical stages is key for understanding whether drugs are efficacious
in slowing or reversing disease. So this is a very important study, but it's
difficult to get funded because one needs to demonstrate
1) an existing infrastructure and the ability to collect
these kind of data and
2) preliminary data that look interesting enough to convince
others that limited federal research dollars should be spent here.
In fact,
Drs Rosen and Boeve had twice applied to the NIH for funding but had been
denied based on lack of preliminary data.
With the inclusion of these new data, which was funded by your
donations, they were awarded the grant --
details of their award can be found at http://projectreporter.nih.gov/project_info_description.cfm?aid=8760412&icde=22317742
 |
| 2014 - Mom was survived by her father ("Grandpop/Jack" and 5 (soon to be 7) grandchildren (L-R: Emma, Henry, Finn, Lily and Josh). We will carry on, but we will never forget. |
About the trial:
The below is provided by Bluefield project and excerpt from
the FORUM press release explaining the significance and hope of this
trial:
“The trial will focus on what is known as FRM-0334. A
mutation in one of the two copies of the progranulin gene that an individual
carries* results in abnormally low levels of progranulin protein and culminates
in the development of FTD.
(*Note: (you
receive a copy of progranulin from each parent, see the post on the science on
the March 13th, 2014 –“It’s Already Been a Year; FTD/PPA Explained: here”
for more details)
Therefore,
drugs that elevate progranulin levels by increasing gene expression from the
second, unmutated copy of progranulin hold promise as potential therapeutics if
they are able to restore levels in mutation carriers.
...FRM-0334
is a brain-penetrant histone deacetylase inhibitor (HDACi) that increased
progranulin expression in cultured rodent neurons
and, most importantly, in cell lines derived from patients carrying progranulin
mutations. Phase 1 safety studies [completed] showed no toxicity or side effects.
And now, on to phase 2 – clinical trials:
FORUM’s
clinical trial will enroll 30 individuals at multiple participating research
sites across the United States and Europe. Individuals must carry a mutation in
progranulin and know their mutation status. Trial participants will receive
either FRM-0334 (low or high dose) or placebo for 28 days, and progranulin
levels in both plasma and cerebral spinal fluid will be measured before and
during the dosing regimen to determine if FRM-0334 raises progranulin protein
levels.”
 |
| 2007, a year before diagnosis, - I am so grateful for Mom to see me graduate! |
Want to
learn more? Below Additional details and
links:
Laura Mitic, from the Bluefield project explains more here: http://www.bluefieldproject.org/news/phase-2-trial-in-progranulin-deficient-ftd-announced
Interested in learning what other dementia related clinics
trials are out there? Another great
place for clinical trial info is the federal website - https://clinicaltrials.gov/ct2/show/NCT02149160?term=FRM-0334&rank=1
