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Tuesday, May 3, 2016

Running in Honor of Hayden

Please support me on my Dipsea run honoring Hayden and FOP research by donating to the International FOP Association.  Click here to make a donation.


3rd flight of the Dipsea Steps in
Mill Valley
On Sunday June 12th, I will run the 106th Dipsea Race in honor of Hayden, to bring awareness for FOP and to raise funds for research.  The Dipsea Race is a 7.4 mile trail race from Mill Valley through Muir Wood and ending in Stinson Beach.  600+ stairs are scattered throughout the race. 

Fibrodysplasia Ossificans Progressiva is a rare and debilitating genetic condition that essentially turns muscle into bone, creating a second skeleton in the body.  Currently there is no known cure.  There are 800 people in the world affected with FOP -  285 of those people are here in the United States.  

Hayden was diagnosed with FOP almost 14 years ago.  Since then, the FOP lab at the University of Pennsylvania, has discovered that the ACVR1 gene causes FOP.  Armed with that information, the FOP Lab in conjunction with the International FOP Association, have reached out to pharmaceutical companies to explore the possibility of a cure.

Hayden and his sister Elsa
Christmas 2015.





















Today, we are in Phase 2 drug trails with Clementia Pharmaceuticals for a drug called Palovarotine.  The drug is showing much promise.  Hayden is currently in the process of enrolling in Clementia's Natural History Study which will help researchers understand the progression of FOP and how an investigational treatment might affect the course of the disease. 

FOP is designated as a rare disease by National Organization for Rare Diseases.  Few rare diseases have a therapy or cure.  Most funds for research for a rare disease come soley from family fundraisers.  The FOP lab at the Department of Orthopaedic Surgery at U of Penn has a budget of $1.5 million/year for research.  75% of these funds come from family fundraising and donations.  25% come from institutional support (NIH/NIAMS, Orthopaedic Research & Education Foundation).  


Hayden and his cousins on
his 16th birthday this year.
Please support me on my Dipsea run honoring Hayden and FOP research by donating to the International FOP Association.  Click here to make a donation.

To learn more about the International FOP Association go to www.ifopa.org.




Monday, May 2, 2016

Quieting cells' low-oxygen alarm stops flare-ups in rare bone disorder

PUBLIC RELEASE: 

Quieting cells' low-oxygen alarm stops flare-ups in rare bone disorder

UNIVERSITY OF PENNSYLVANIA SCHOOL OF MEDICINE
PHILADELPHIA - The cellular response to the lack of oxygen fans the flames of flare-ups in a rare bone disorder. In fibrodysplasia ossificans progressiva (FOP), a mutation triggers bone growth in muscles, which limits motion, breathing, and swallowing, among a host of progressive symptoms.
Scientists from the Center for Research in FOP and Related Disorders at the Perelman School of Medicine at the University of Pennsylvania and colleagues examined the critical role of tissue hypoxia, or oxygen starvation, in the induction and amplification of FOP lesions, also called flare-ups.
The research team, led by Haitao Wang, PhD, a senior research investigator, Robert Pignolo, MD, PhD, an associate professor in the division of Geriatrics and the Ian Cali Distinguished Clinician-Scientist at the Center, and Frederick S. Kaplan, MD, the Isaac & Rose Nassau Professor of Orthopaedic Molecular Medicine and Chief of the division of Molecular Orthopaedic Medicine, published their findings in the Journal of Bone and Mineral Research this month.
They showed that cells from FOP lesions in humans and in a mouse model of FOP are markedly oxygen-starved and that this hypoxia triggers a molecular alarm orchestrated by the HIF-1α protein. Surprisingly, HIF-1α dramatically amplifies the already mutant bone morphogenetic protein (BMP) signaling in the oxygen-starved cells and stimulates heterotopic ossification, the abnormal metamorphosis of muscle to bone that occurs in FOP. Most importantly, when the team disabled the HIF-1α cellular alarm, BMP signaling in human FOP bone progenitor cells was restored to levels comparable to cells in normal oxygen. This adjustment profoundly reduced heterotopic ossification and the resulting disability in the FOP mouse.
A Tantalizing Lead
In 2006, Penn researchers led by Kaplan and Eileen Shore, PhD, the Cali-Weldon Professor of FOP Research and a co-author on the current study, discovered how a mutation in the gene for a BMP receptor called Activin Receptor A type I (ACVR1) occurs in all individuals who have classic FOP. The mutation in ACVR1 (mACVR1) causes the ACVR1 protein, a cell surface receptor, to be mildly overactive, thereby stimulating the BMP pathway continuously, like a faucet that drips water when it should be turned off. However, despite the presence of mACVR1 in all FOP patients, individuals with FOP do not form bone continuously but rather episodically during flare-ups, an important clue that suggested that something else fuels the process of lesion formation.
A tantalizing lead came from studying FOP lesions themselves. Importantly, all FOP flare-ups, whether spontaneous or triggered by trauma, are associated with inflammation, also a well-known cause of oxygen starvation in cells.
"Hypoxia can occur for many reasons, but in early FOP flare-ups, we speculated that hypoxia might result from the inflammatory microenvironment in lesions," Kaplan said. "This happens when oxygen supply to the damaged tissue is impaired and oxygen demand by the damaged cells greatly exceeds its supply."
Indeed, every cell continuously produces HIF-1α but rapidly destroys it when the cell has an adequate supply of oxygen. When a cell is oxygen starved, the enzymes that inactivate HIF-1α instantly cease to function, allowing HIF-1α to escape destruction, enter the nucleus of the cell, and trigger an alarm that instructs genes to adapt to a low-oxygen microenvironment. This chain of events allows the cell to survive.
The current study showed that HIF-1α inhibitors, specifically the cancer drug imatinib (Gleevec), the natural product apigenin, and the small molecule PX-478, potently inhibit dysregulated BMP signaling induced by HIF-1α in cells, as well as heterotopic ossification following tissue injury in a mouse model of FOP.
"The implications for targeted clinical trials and for compassionate clinical use of HIF-1α inhibitors in the treatment of FOP flare-ups are promising, however we need more data on dosing, duration, timing, rebound, resistance and long-term safety," Pignolo said.
"Our study provides profound insight into the role of cellular hypoxia in FOP flare-ups and shows that cellular oxygen sensing through HIF-1α is a critical regulator of the BMP pathway and heterotopic ossification in FOP," Kaplan said.
The findings support the hypothesis that FOP lesions thrive in a hypoxic microenvironment, not simply due to oxygen deprivation, but also because of a maladaptive response to hypoxia by the HIF-1α molecular alarm, similar to that seen in cancer. Most importantly for individuals with FOP, the study identifies HIF-1α as a therapeutic target -- knowledge that will likely contribute to the development of more effective treatments for FOP and related common disorders of heterotopic ossification.
###
This research was supported in part by the International Fibrodysplasia Ossificans Progressiva Association, the Center for Research in FOP and Related Disorders, the Ian Cali Endowment for FOP Research, the Whitney Weldon Endowment for FOP Research, the Cali-Weldon FOP Pre-Clinical Drug Testing Program, the Brinkman Family, the Isaac and Rose Nassau Professorship of Orthopaedic Molecular Medicine, the Cali-Weldon Research Professorship in FOP, the Ian Cali Clinical and Research Scholarship, the Rita Allen Foundation, the Roemex Fellowship for FOP Research, the McGuire Fund for FOP Research, the Ashley Martucci Fund for FOP Research, the Penn Center for Musculoskeletal Disorders, and the National Institutes of Health (NIH R01-AR41916).

Saturday, April 23, 2016

10 Years Ago Today

In early, 2006, I heard the words through the telephone, “Megan, they have discovered the gene.” It was a phone call from the then president of the board for the IFOPA, Amanda Cali, telling me that the FOP lab had discovered that the ACVR1 gene is the cause of FOP.  I can’t tell you the emotions that ran through me.  I was so ecstatic; all I could do was cry. 

The lead researcher at the FOP Lab at U of Penn, Dr.Frederick Kaplan, had been in Germany for work. He received a call from Meiqui Xu who was part of the research team at U of Penn. Meiqui told Dr. Kaplan that she was certain she had found the gene that caused FOP. Cautiously the team began the process of double and triple checking their findings until they were certain that the ACVR1gene was in fact the one, which causes FOP.

ACVR1 Gene
On April 23, 2006, ten years ago today, Penn Medicine held a press conference to announce the findings.  I was honored to be able to be in Pennsylvania to share the joy and celebrate with Jeannie Peeper, the founder of the IFOPA, Dr. Kaplan and Dr. Shore, along with the researchers from the FOP Lab and of course many of the families from the FOP community.

In honor of that important announcement, April 23rd became International FOP Awareness Day.
Post Press Conference with other FOP Moms - from left to right
Hillary Weldon, Amanda Cali, Jennifer Snow and Jerry Licht.
After Hayden was diagnosed in 2002, I started researching about FOP and rare diseases. I learned words like “orphan drugs”, “mouse model”, “humanitarian exception”, “BNP Receptors”, “Noggin Gene”and “heterotopic” to name a few.   Of all the words that were new to me one word kept me going, “HOPE”.  

Of the 7,000 rare diseases listed in the NORD directory, only 4% have a cure or therapy. Today, the IFOPA is in drug trials with Clementia Pharmaceuticals with a drug that shows strong hope of bringing a therapy for our FOP Community.  Recently the Journal of Bone and Mineral Research published online a non-Clementia sponsored study describing palovarotene’s novel, beneficial effects on spontaneous heterotopic ossification, mobility, and skeletal growth in mouse models of fibrodysplasia ossificans progressiva.

So much has happened since Hayden’s diagnosis. It is truly amazing. What a journey it has been. Thank you all for your support.
#FeelingBlessed

Monday, February 29, 2016

World Rare Disease Day 2106

Today, February 29th, 
is 
World Rare Disease Day

It seems fitting that today the 40th and last participant has enrolled into the Clementia Phase 2 clinical trail that is investigating palovartene for the treatment of FOP.

When Hayden was diagnosed September 11, 2002, hope seemed to 
very, very far away.  However the following pretty much sums up the FOP Community.
"Alone we are rare. Together we are strong."

Nothing demonstrates this more that the determination of our families who fundraise, our board members who guide us along our mission and the researchers who are continually on a quest to discover a cure.

World Rare Disease Day is an annual observance held on the last day of February to raise awareness for rare diseases and improve access to treatments and medical representaiotn for individuals with rare diseases and their families. 


Hayden in Tahoe - 4th of July 2015

Saturday, February 28, 2015

Rare Disease Day 2015

rare/re(ə)r/ Adjective
1.) marked by unusual quality, merit or appeal, distinctive
2.) seldom occuring or found uncommonly

Typically when we think of something as rare, 
we think of something special, 
unique or hard to come by.

Something spectacular such as the Hope Diamond,

 or discovering long, lost ancient ruins


or even a fossilized sand dollar 
such as the one I found recently on the beach.


Rarely, no pun intended, do we like to associate 
the word "rare" with an illness. 
However there is nothing spectacular about 
receiving a diagnosis of a rare disease. 
It is, in a word, devastating.

Less than 5% of rare diseases have 
any therapies or treatments.

There are 7,000 identified rare diseases with no cures.

350 million people have a rare disease.  
That is more than all those with 
Cancer and AIDS combined.

Finding funding for research, advocacy 
and community outreach 
for these orphan diseases, 
as they are called, is beyond challenging.

However within this rare community of people,  
there is something special about a rare disease, 
the people.

These special people are… 

...the scientists who study it,
Researchers in the FOP lab at University of Pennsylvania.
Meiqi Xu, Drs Frederick Kapkab and Eileen Shore

...the patients and families who live with it
Hayden Pheif, skiing in 2008, at the Far West
Disabled Sports Center in Alpine Meadows, CA

...the amazing people who have only yet learned of FOP and
 will go to "great lengths" to fundraise for research
which will help to find a cure
Team "Girls with Grit" ran the Napa Valley Ragnar
(36 hour - 206 Mile) Relay in September to as a fundraiser
for Hayden's Hope
.

...Jeannie Peeper, the most inspirational woman I know.
Jeannie, who has FOP, started the International FOP 
Association 25 years ago. Her goal was and
is to raise awareness, provide outreach to
families and those effected with FOP as well as
to provide a 501c to support fundraisers for research.  
Today, because of Jeannie,
Clementia Pharmaceuticals is in Stage Two of
Drug Trials for a therapy for those with FOP.
Jeannie Peeper with Dr. Frederick Kaplan,
head of FOP research at U of Penn, at the 25th
anniversary IFOPA celebration.

These people are rare in a very special way.
They give us hope.

Even though the people afflicted with rare diseases 
create a very large community, 
their conditions remain largely unknown 
to the vast majority of the world population.  

Today, February 28th, 
is 
Global Rare Disease Day.

This day was created in the United States 
by the National Organization for Rare Diseases (NORD) 
to raise awareness and 
increase advocacy for these special diseases,
as well as to provide hope to the 
patients and families afflicted by them.

Please join me in by honoring those whocourageously live with a

Rare Disease by donating to the

IFOPA 

Friday, February 27, 2015

Rare Disease Day - Tomorrow February 28th

Thank you to Global Genes Project for this great article.

RARE Diseases: Facts and Statistics

Statistics and Figures on Prevalence of 
Genetic and Rare Diseases
Although rare and genetic diseases, and many
times the symptoms, are uncommon to most doctors,
rare diseases as a whole represent a large medical
challenge. Combine this with the lack of financial
or market incentives to treat or cure rare diseases,
and you have a serious public health problem.
Here are a few statistics and facts to illustrate the
breadth of the rare disease problem worldwide.










There are approximately 7,000 different types of
rare diseases and disorders, with more being
discovered each day

30 million people in the United States are living with
rare diseases. This equates to 1 in 10 Americans or
10% of the U.S. population

Similar to the United States, Europe has approximately
30 million people living with rare diseases. It is estimated
that 350 million people worldwide suffer from rare disease

If all of the people with rare diseases lived in one country,
it would be the world’s 3rd most populous country

In the United States, a condition is considered “rare”
if it affects fewer than 200,000 persons combined in
a particular rare disease group. International definitions
on rare diseases vary. For example in the UK, a
disease is considered rare if it affects fewer than 50,000
citizens per disease

80% of rare diseases are genetic in origin, and thus
are present throughout a person’s life, even if symptoms
do not immediately appear

Approximately 50% of the people affected by
rare diseases are children

30% of children with rare disease will not live to see
their 5th birthday

Rare diseases are responsible for 35% of deaths
in the first year of life

The prevalence distribution of rare diseases is
skewed – 80% of all rare disease patients are 
affected by approximately 350 rare diseases

According to the Kakkis EveryLife Foundation,
95% of rare diseases have not one single FDA
approved drug treatment

During the first 25 years of the Orphan Drug Act
(passed in 1983), only 326 new drugs were 
approved by the FDA and brought 
to market for all rare disease patients combined

According to the National Institutes of Health Office 
of Rare Disease Research, approximately 6% of
the inquiries made to the Genetic and Rare 
Disease Information Center (GARD) are in
reference to an undiagnosed disease

Approximately 50% of rare diseases do not have a
disease specific foundation supporting or
researching their rare disease

Friday, December 5, 2014

A Hope for FOP & Hayden: FDA Approves Fast-Track Designation for Palovarotene


Clementia Receives Fast-Track Designation from FDA for Palovarotene


MONTREAL, Dec. 1, 2014
The IFOPA is pleased to share news that Clementia Pharmaceuticals received Fast Track Designation for palovarotene for the treatment of FOP.  This designation does not impact the clinical trial that is taking place for our FOP community.  To download and read the entire announcement please click on Clementia Receives Fast-Track Designation from FDA for Palovarotene.