Research continues as 2nd ‘Run for Broxton’ nears in memory of Gilbert boy - East Valley Tribune: Health

Research continues as 2nd ‘Run for Broxton’ nears in memory of Gilbert boy

Print
Font Size:
Default font size
Larger font size

Posted: Tuesday, February 5, 2013 7:37 pm | Updated: 8:21 am, Thu Feb 7, 2013.

Editor’s note: This piece is a follow-up to a pair of 2012 Tribune stories on the fight for life by Broxton Taylor of Gilbert, who died in April 2012 of complications from Batten Disease. Find those stories at evtnow.com/run4broxton and evtnow.com/broxtonlegacy. The second “Run for Broxton” fundraising event is scheduled for Sunday. For more details, visit runforbroxton.com. A longer version of this piece -- the author's original scientific journal article -- can be found at the link below.



Having a child reach toddler age involves many exciting new questions and avenues for parents: What should I feed my child? What books should I read her? Will he play soccer or baseball? How should I discipline my child?

What isn’t nearly as exciting to wonder: How do I insert a feeding tube? What combination of antidepressants and seizure medications should my child take? If my child stops breathing, do I rush him to the hospital?

The latter questions are those of parents who have a child with Infantile Neuronal Ceroid Lipofuscinosis (iNCL), a genetically inherited neurodegenerative disorder also known as a subset of Batten Disease.

While the disease is rare – 1 in 25,000 live births – it did shatter a Gilbert family’s world last year when it took the life of 28-month-old Broxton Taylor on April 20.

In the upcoming week, East Valley residents will gather again for the “Run for Broxton,” a fundraising event to help fund research on infantile Batten Disease. Scheduled for Sunday, Feb. 10, at Freestone Park in Gilbert, proceeds will go to the Batten Disease Support and Research Association. Last year’s debut event drew more than 500 participants for a 1K Fun Run and a 5K Run, and registration for this year’s event is available at runforbroxton.com.

A child born with the disease seems to develop normally until about 1 year old. The genetic defects begin to physically manifest with regression from walking to crawling, muscle spasms leading to seizures, and gradual blindness by 2 years of age.

Broxton’s death was tragic, unpreventable, and untreatable with the most current and innovative science.

Infantile Batten Disease begins with one or more mutations in a specific gene (CLN1), which encodes a protein called Palmitoyl Protein Thioesterase 1 (PPT1). The gene serves as a blueprint for building the protein (PPT1), which performs a very specific function based on its structure. If the blueprint (the CLN1 gene) is flawed, it can cripple the protein and deem it useless.

Every protein manufactured in the body has a specific function and location. PPT1 works in a part of the cell called the lysosome. Lysosomes serve as garbage disposals for the cell, digesting unused and malformed molecular waste. PPT1 is essentially a blade of the garbage disposal, cutting specific parts of proteins so that they can undergo further digestion. In iNCL, undigested proteins accumulate in and kill the brain cells of affected infants causing Batten Disease symptoms.

The condition is complex, but an undiscovered cure does not mean that modern technology and research are failing. Dozens of determined scientists are clarifying the intricate details of the disease process and finding promising results for potential cures.

Kathy Partin, PhD, of Colorado State University explains the difficulty of research progress of rare diseases.

“We, as a society, have decided that drug development is under capitalistic rules,” she said. “We don’t want the government to subsidize it. The problem... is that they make business decisions based on business outcomes and not individual outcomes.”

Partin’s research focuses the function of glutamate receptors, a main source of communication in the nervous system. Though Partin does not work directly with Batten Disease, her research was cited recently in Rozzy Finn’s scientific article in the Journal of Neuroscience Research. Finn’s thesis, conducted at the University of Rochester School of Medicine and Dentistry in New York, revealed that glutamate receptor activity may play a key role in brain deterioration in patients with infantile Batten Disease.

Also promising for iNCL research, is the 2010 work of Dr. Glyn Dawson and his son Dr. Philip Dawson, which focused on a cure for infantile Batten Disease through the function of chaperones.

A chaperone is a molecular tool manufactured in a lab, but introduced into a person’s biological system to increase function of non-working proteins. These chaperones are mild inhibitors of the target protein. What would debilitate a normal protein by its chemical interaction, chaperones actually increase the function in mutated proteins. This is like using a crutch. Use of a crutch will slow down a healthy person, but increases mobility in a handicapped person. Thus, the chaperone only works on proteins with partial functionality.

Dr. Philip Dawson explains: “There is a mutation which manufactures the protein halfway and then stops; we can’t do anything about that. But, there are a significant number of missense mutations where the protein is just a little bit destabilized [and] is prematurely degraded. Hopefully, we can tickle that pathway a little bit.”

The Dawsons did indeed tickle that pathway. Their test results show that use of chaperones restored two-fold function to PPT1 (the mutation in iNCL). “It has been shown that you don’t need much enzyme activity to make it to adulthood,” Dawson says.

The specific exploration of technology with infantile Batten Disease, such as use of chaperones, reveals treatment options in other neurological diseases such as Huntington’s and Alzheimer’s Disease.

Unfortunately because of the rarity of the Batten Disease, it is hard to take experimentation from Phase 1 to Phase 3, where it can be tested on humans.

“It’s frustrating for making a grant proposal. People start nitpicking at little details, thinking that this might not be the best therapy,” Dawson explains. “Do you realize that there is no therapy?”

Fortunately, increased awareness and research of this disease is growing. During my research I spoke with four different doctors in four different time zones with four different intentions, all working towards a cure for one single disease.

Both Finn’s article and the Dawsons’ research have been featured on BDSRA.org. BDSRA is a non-profit organization designed to promote research for Batten Disease and provide support for families of victims.

And of great importance, the general public is becoming more aware of the disease. A specific cure may depend on the molecular interactions of bioprocesses that only a few can understand. But, what keeps those brilliant minds funded and working, is the support of people like you and me.



LINK: Read the full scholarly work of author Daniel Gutman on Batten Disease ["iNCL -- A deadly disease testing technological boundaries in medicine]

More about

More about

  • Discuss

Attorney General Forum - Question 1

Attorney General candidates Republican Mark Brnovich and Democrat Felecia Rotellini debate at ...

Facebook

EastValleyTribune.com on Facebook

Twitter

EastValleyTribune.com on Twitter

Google+

EastValleyTribune.com on Google+

RSS

Subscribe to EastValleyTribune.com via RSS

RSS Feeds

Spacer4px
Your Az Jobs