This week the University of Michigan Football team lost a
crucial component of the team—5 year-old Chad Carr. Chad, grandson to Lloyd
Carr who coached at Michigan from 1995-2008, died yesterday after a year-long
battle with an inoperable brain tumor. Chad was diagnosed with a Diffuse
Intrinsic Pontine Glioma when he was just 4 years of age presenting with
symptoms including difficulty controlling facial muscles, speech problems, and uncontrolled
eye movements due to cranial nerve damage as well as muscle weakness in the
arms and legs. These symptoms are characteristic of the tumor, which is found
in the pons area of the brainstem—we know this area is responsible for
autonomic nervous functions such as breathing, blinking, and cardiac function.
Although little is known about how the tumor develops, cases like Chad’s have
allowed research shedding light on the genetic mutations which may be
responsible for this menacing disease. However, despite recent progress in
research on this tumor, it remains essentially untreatable as it envelops
healthy brain tissue rendering it resistant to chemotherapy and impossible to
surgically remove the tumor without removing healthy areas of the brain.
After receiving the heartbreaking news of Chad’s aggressive
brain tumor, his family decided to use his last 9-12 months to enjoy life and
raise awareness about Diffuse Intrinsic Pontine Glioma (DIPG). Utilizing the
Big 10 Football platform, Chad united Michigan’s biggest rivals, Ohio State and
Michigan State, as hundreds of thousands of people encouraged his battle with
the hashtag #ChadTough. This gave rise to the Chad Tough Foundation ( www.chadtough.org) where Michigan fans,
rivals, and even people who don’t care much for college football (if those kind
of people exist) can donate to raise funds for NIPG research.
Many other families have also been affected by NIPG
(approximately 300 children are diagnosed per year in the U.S.) and have similar stories
regarding a hopeless prognosis. Last week, one family chose to donate
their son’s brain to Stanford Medicine for research to come up with possible
treatment and prevention strategies. This donated tissue allowed Dr. Michelle
Monje to create the first mouse model of the tumor revealing immense information
about the tumor’s mechanism; as the tumor grows, it prevents neuroplasticity to
allow more space for the proliferating tumor cells. Her team is now beginning
clinical trials for a drug that elongates the mouse’s life which may prove
efficient in humans as well. Although over $1 million have been donated to DIPG
research including funds from the Chad Tough Foundation, more awareness and
funding continues to be necessary to develop efficient treatment strategies.
In the spirit of Thanksgiving and college football rivalry
week, I encourage you all to remember Chad Carr’s bravery and strength as you
devour your turkeys and, of course, cheer for Michigan over Ohio State!
It is so devastating to learn about Diffuse Intrinsic Pontine Gliomas and Chad's case. As you mentioned, they are almost impossible to treat, but I wanted to know how much and what research was being conducted on DIPGs. I came across a few different articles that focused on different chemotherapy combinations, none of which looked extremely promising in treating DIPGs. Others looked into genome sequencing and determining if they are any differences in patients with DIPGs compared to healthy individuals. The results of the genome sequencing left the researchers with a few leads, mainly, one article found that there were differences in the expression of the platelet-derived growth factor receptor alpha.
ReplyDeleteWith today's technology focused on genetics and sequencing entire genomes, I have noticed that new research is focused on finding the root causes or differences that lead to diseases, rather than just looking at finding a quick treatment. I think that this is important to note this shift in research because there are both pros and cons of finding a cause first rather than trying to see what treatments work best. In the past, different combinations of chemotherapy would be experimented with, but now we are looking at how genes play a role in developing diseases such as cancer and then directing treatments at these differences that are discovered. And although this gene-focused research may be more effective in finding a treatment, it does take a longer amount of time and many individuals are left with no treatment options for the time being (like Chad). So it raises the question: which type of research should be carried out and on what timeline? I don't think there is necessarily a right answer, but it's essential to understand what research is being done and why.
http://jco.ascopubs.org/content/28/8/1337.short
The strength of Chad and all of those affected by DIPG is certainly admired. Similarly, glioblastoma multiforme (GBM) in adults remains essentially untreatable; 5-year survival of GBM patients after aggressive treatment is less than 5%. I recently read a study looking to increase the efficacy of the chemotherapeutic drug temozolomide (TMZ) in GBM tumors that are resistant to chemotherapy. In TMZ-resistant brain tumors, the lethal DNA lesions cause by TMZ in fast-dividing cancer cells is quickly repaired by the enzyme O-6-methylguanine-DNA methyltransferase (MGMT). TMZ resistance is also controlled by the gap junction protein Cx43 so by inhibiting Cx43 channels via alpha-CT1, MGMT-deficient GBM cells became sensitive to TMZ treatment. Moreover, alpha-CT1 was found to block the AKT/AMPK signaling pathway and indirectly induce apoptosis. So although the prognoses of these rare and devastating tumors are currently poor, combining alpha-CT1 (the Cx43 inhibitor) with TMZ could enhance therapeutic responses in these chemotherapy-resistant cancers.
ReplyDeletehttp://cancerres.aacrjournals.org/content/early/2015/11/11/0008-5472.CAN-15-1286.long