Their Ultimate Last Stand- McKenna Claire Foundation

When the beautiful, green-eyed, blond 7 year-old California kid, McKenna Claire Wetzel, started to throw up in January 2011 it was just thought to be the flu that had been going around.   After of week of illness and a couple visits to the doctor, her parents started to notice a wandering left eye.   The CT Scan that followed found the DIPG.

Good friends and good times- two of life's greatest gifts.    MckKenna's parents worked hard for both.   They had been told that this tumor was not survivable.   Thus, they told their oldest child that they were doing thing to make Mckenna feel better- sadly not to cure her.   She traveled to Hawaii, to tapings of both American Idol and Dancing with the Stars and sat on the floor at the Laker's game.   She continued to go to second grade and every Tuesday night was "homework parties" at her house.  The parties were more about community and friendship than homework.   As things worsened her friend, Katie, would sit for hours holding McKenna's hand in silence.  

Just six months from hearing DIPG, McKenna passed away.   As devastating as this was, the Wetzel's were making one "last stand" against the tumor.   They decided to donate Mckenna's tumor to Michele Monje's lab at Stanford.  A lab tech from Stanford flew down as a guardian for this precious gift as it came to a new home- a place striving to learn how get rid of "that stupid tumor".

However, the Wetzel's realized that funded research would be able to do more.  To honor McKenna and "perpetuate the sense of community",  the McKenna Claire Foundation was born.    In less than 2 years the foundation has raised approximately a half million dollars.    One amazing thing was last May (Brain Cancer Awareness Month) the Chevron Corporation raised $292,466 at some of their California convenience stores.

These funds have been provided to Michele Monje's lab at Stanford which had grown a cell line from McKenna's tumor.   And although cell lines haven't been easy to transport, Michele Monje's lab seems to have overcome this hurdle.   McKenna's tumor now is also being studied by researchers in England and Australia!

Some of that funding had gone to fund the position of "tumor cell line guardian".   OK,  Anitha Pannuswami's official title is laboratory manager at Monje’s lab at Stanford.   Often times salary funding is not part of grants, but I believe this has been a important factor in being able to do more in DIPG research.    Anitha Pannuswami's job is to watch over McKenna's tumor as well as 5 other children's at the Monje lab.   She also handles shipping them in ice to any researcher in the world who wishes to study DIPG.  This is defnitely increasing DIPG reasearch internationally.

This May's Brain Cancer Awareness Month, the Chevron Corporation has expanded their support through their convenience stores throughout California.  The Mckenna Claire Foundation has several other events already planned for 2013. 

McKenna's tumor is flying like a butterfly around the world.   Without a doubt, the McKenna Claire Foundation  and the targeted partnership with Stanford is changing the landscape for DIPG Research.   I predict both will be well worth watching.

References:
Tumor that killed girl could keep others alive
http://www.bendbulletin.com/article/20130427/NEWS0107/304270355/

Chevron customers raise $292,466 for McKenna Clair Foundation fight against pediatric cancer
http://www.orangecounty.com/articles/chevron-41266-foundation-claire.html#

Mckenna Claire Foundation
http://mckennaclairefoundation.org/

Focus on Research: 3 New DIPG Abstract This Week!

One of the frustrating things about medical research is the delay between when research is presented at a scientific meeting and when it actually gets to publication.   Unfortunately, sometimes the gap is more than a year.   For this reason, I trawl around the meeting abstracts which might have potential.    One such meeting is the American Association of Cancer Research (AACR) concluding it's five-day Annual Meeting tomorrow.    I am thrilled to report there are DIPG presentations at this meeting.

Here are the citations for the three presented abstracts:

1)  Nathalene Truffaux, Ludivine Le Dret, Stephanie Puget, Gilles Vassal, Birgit Geoerger, Jacques Grill.
Activity of dasatinib and potential escape mechanisms in diffuse intrinsic pontine glioma (DIPG) models
 In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; 2013 {Abstract 2763}

2)  Sridevi Yadavilli, Madhuri Kambhampati, Oren J. Becher, Tobey MacDonald, Ravi Bellamkonda, Roger J. Packer, Javad Nazarian. 
NG2 upregulation and its defective asymmetric distribution in pediatric brainstem glioma and diffuse intrinsic pontine glioma
In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; 2013. {Abstract 5004}

3)  Marianne Hutt, Wendy Goldstein, Javad Nazarian, Antoinette Price, Kah Jing Lim, Katherine Warren, Howard Chang, Charles Eberhart, Eric Raabe.
Targeting the Notch and mTOR pathways in diffuse intrinsic pontine glioma
In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; 2013.  {Abstract 5049}

The first abstract is from the French researchers that have pioneered the way for biopsies.  The second is from National Children's in DC, Duke and Emory/Georgia Institute of Technology.  The third is from the Mid Atlantic DIPG Consortium (MADC).  The MADC abstract appears to be an extension of the abstract we highlighted here on March 23this year.

As the abstracts are meant for a group of researchers, they are most definitely highly scientific.  Here is one thing to take away-  it is possible to establish cell lines from freshly biopsied DIPG material.   The French group has been able to establish 12 lines in this way!  

Dylan Warriors- a pivotal change for DIPG

The last two posts about the sonic hedgehog pathway have been quite medical.   When trying to decipher the medical terms it is easy to miss the amazing lengths families have gone to try to make a difference in the course of DIPG.   In this instance, we actually know a specific child and family that started it all- the Jewett family.  This is a remarkable story of a family and a researcher joining forces to completely change the world for DIPG.  Through the donation of Dylan's tumor to Stanford the entire landscape for DIPG research has changed.

The thinking has changed from "it isn't possible" to "it is possible"!

*It is possible that parents will want to donate tumor after their child has died.
*It is possible that we can grow cell lines and make animal models from this donated tissue.
*It is possible from that information we can chose new ways to try to fight DIPG.
*It is possible for families, foundations and researchers to come together to make a difference.

Thank you Jewett family, Dylan's Warriors, Michelle Monje and the doctors at Stanford.

Note:  We now not only do we have that one cell line but more than 30 others DIPG cell lines!

Please watch their story at-
https://www.youtube.com/watch?v=pdFfWhQ9964

References:
Dylan's Warriors- http://curedipg5.com/ or www.facebook.com/CureDIPG

Dylan's Story- http://www.kidsvcancer.org/tissue-donation/information-for-families/donation-stories/dylan/

DIPG Preclinical Consortium-
http://pptiohsu.blogspot.com/2011/12/open-science-forum-dipg-preclinical.html

Vismodegib? Why a Sonic Hedgehog Inhibitor?

Yesterday we posted about the yet-to-be opened Vismodegib trial for refractory DIPGs.   Although the trial rationale isn't listed in the clinicaltrials.gov posting, for those following DIPG publications  a sonic hedgehog inhibitor will likely recall Dr. Michelle Monje's publication two years ago.  In this publication, the authors indicate that Hedgehog signaling happens in DIPG propagation and that this could lead to "unique therapeutic avenues to treat DIPG".

Sonic hedgehog inhibition has been a subject with medulloblastoma for years as it is estimated that about 1/3 of medulloblastoma tumors may have a sonic hedgehog driver.   In fact there are two open trials listed in clinicaltrials.gov for recurrent medulloblastoma.     Thus, there is an agent already been tried in kids with brain tumors and a pathway found in molecular analysis of a DIPG.   This trial seems to put those to items together to try something new for DIPG.

The full text of the Monje paper is available.  Warning it is highly medical.    However, it appears to be a seminal article for DIPG for several reasons.
1) It highlighted that valuable information can be obtained from post-mortem donation.
2) It showed for the first time that neurospheres/cell lines can be developed from post-mortem tissue
3) It explicitly stated the relationship between brain development and the typical timing of DIPG occurrence.

The paper points out there are two very different general types of pontine tumors- those that occur in in the dorsal pons (pontine tegmentum) and those that develop in the vental pons (base of the pons).  Dorsal pontine tumors have very favorable courses with survival for years or decade, where as vental pontine tumors are often aggressive, diffuse and lead to death with in a year of so.  They feel that they identified a neural precursor-like cell populations (pretty much like stem cells) that has been seen in the ventral pons.   The interesting thing is this cell is seen most durin middle childhood- the exact same time as pediatric DIPG occurs.  This suggests there  might be something that goes wrong in these cells wich may be the reason for DIPGs to strike this age and this region of the brain.

The article below is not easy reading but worthwhile not only to further understand this upcoming trial but also to gain further insight into the role neurodevelopmental biology will likely play in unravelling DIPG.

References:
Hedgehog-responsive candidate cell of origin for diffuse intrinsic pontine glioma
Free Full Text-  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3060250/