CURE Ally Dr. Marcelo Diaz-Bustamante Works to Find a CURE for his Daughter’s Epilepsy

Dr. Marcelo Diaz-Bustamante of Johns Hopkins University is not only a devoted father; he is also a devoted researcher studying infantile spasms, a severe form of childhood-onset epilepsy. Dr. Diaz-Bustamante’s daughter Myriam was diagnosed with the disorder in 2016.

Infantile spasms is a hard-to-treat form of epilepsy that normally starts in the first year of life and is characterized by subtle seizures, abnormal brain activity, and developmental delay or regression.

Faced with Myriam’s daunting diagnosis, Dr. Diaz-Bustamante had his daughter’s genes sequenced as part of CURE’s Epilepsy Genetics Initiative (EGI). EGI examines genetic information to uncover the causes of epilepsy and advance precision medicine. Amazingly, gene sequencing pinpointed the cause of Myriam’s infantile spasms to a mutation in a GABA receptor, which is a type of neuronal receptor important in maintaining the balance of excitatory and inhibitory activity in the brain. After learning of this mutation, Dr. Diaz-Bustamante changed his research focus to devote himself to studying this infantile spasms-causing mutation.

Since his daughter’s diagnosis, Dr. Diaz-Bustamante has formed a deep connection with CURE. He has hosted a CURE-sponsored seminar at Johns Hopkins University and has participated in CURE’s Day of Science events. Dr. Diaz-Bustamante credits CURE with providing both education about and a human face to epilepsy, creating a feeling that he and his family are not alone in their fight.

In fact, Dr. Diaz-Bustamante believes the biggest challenge facing parents whose child has been diagnosed with infantile spasms is a lack of hope; “It is difficult to remain hopeful with all of the scary information available on the internet, coupled with many pediatricians’ lack of knowledge about the disorder.” Still, he is hopeful about the future of epilepsy research, noting that growth in the field over the past 10 years has been exponential with heightened understanding of epilepsy and increased research into new treatments and therapies.

While Myriam has gone through more than 5 different types of treatments and therapies to control her spasms, we are happy to report that she is finally experiencing some improvement. However, Myriam still has a long road ahead of her. There is a continuing need for the devotion of research and resources to uncover the causes of childhood epilepsy. As Dr. Diaz-Bustamante notes, “We have the tools to investigate the causes of epilepsy, but if there isn’t enough money for research, we can’t investigate potential treatments.” CURE agrees. We thank Dr. Diaz-Bustamante for his devotion to finding a cure for infantile spasms.

Study: Detailed Magnetic Resonance Imaging (MRI) Analysis in Infantile Spasms

Purpose: To evaluate initial magnetic resonance imaging (MRI) abnormalities in infantile spasms, correlate them to clinical characteristics, and describe repeat imaging findings.

Methods: A retrospective review of infantile spasm patients was conducted, classifying abnormal MRI into developmental, acquired, and nonspecific subgroups.

Results: MRIs were abnormal in 52 of 71 infantile spasm patients (23 developmental, 23 acquired, and 6 nonspecific) with no correlation to the clinical infantile spasm characteristics. Both developmental and acquired subgroups exhibited cortical gray and/or white matter abnormalities. Additional abnormalities of deep gray structures, brain stem, callosum, and volume loss occurred in the structural acquired subgroup. Repeat MRI showed better definition of the extent of existing malformations.

Conclusion: In structural infantile spasms, developmental/acquired subgroups showed differences in pattern of MRI abnormalities but did not correlate with clinical characteristics.

New Direction For Precision Medicine In Epilepsy

In a new approach to precision medicine research, scientists used bioinformatics tools to identify common features of genes associated with infantile spasms compared to other forms of early life epilepsy. Their analysis, published in PLOS ONE, reveals that infantile spasms are not only unique clinically, but also biologically. Focus on specific biological mechanisms underlying the genes that cause infantile spasms could help find new targets for treatment.

‘Our novel approach marks a paradigm shift in precision medicine from single gene discovery to grouping genes by their underlying biology,’ says lead author Anne Berg, PhD, epilepsy specialist at Ann & Robert H. Lurie Children’s Hospital of Chicago and Research Professor in Pediatrics at Northwestern University Feinberg School of Medicine. ‘To develop new treatments, we can start looking at mechanisms common to many associated genes, instead of trying to therapeutically target one gene at a time. With this approach, we are starting to ask why certain genes are involved, which might help us understand why some treatments are effective and others are not. Such an approach could ultimately help us choose the treatment that mostly precisely matches the genetic signature and biology of the child’s epilepsy.’

‘We used bioinformatics tools to perform what is called gene set enrichment analysis, which means that we looked at common molecular properties of genes that lead to infantile spasms and other types of seizures,’ says Dr. Berg. ‘We examined how these genes function in the cell, in what processes they are involved, where in the cell they are expressed. We found that the genes associated with infantile spasms are uniquely involved in developmental functions within the cell body, which might be linked to why spasms tend to start at the same time in an infant’s development.’

When it comes to Infantile Spasms, families face difficult choices

When Mickie was born, she was a beautiful, normal, healthy baby. Then she began having seizures at the age of three months. Soon thereafter, she was diagnosed with intractable epilepsy and infantile spasms (IS), and her parents were forced to make agonizing decisions about her care.

After eight different medications failed to stop Mickie’s seizures, physicians suggested that a major surgery might be her only hope. Without it, her seizures could eventually prove debilitating or even fatal. The day before Mickie’s first birthday, she underwent brain surgery and has not had a seizure since. Today Mickie is active and healthy but still recovering from the damage inflicted by epilepsy. She undergoes regular therapies to improve her speech and must take anti-seizure medication every day.

Mickie’s quality of life improved with surgery, but for far too many children with infantile spasms, these results are not possible. That is why we hope you consider CURE during your annual holiday giving so that we can continue to drive research forward.

CURE’s Infantile Spasms (IS) Initiative has advanced disease-modifying therapies for kids like Mickie by focusing on the underlying pathology of this syndrome. In a groundbreaking, multidisciplinary “team science” approach, CURE awarded $4.2 million in grants to investigators to advance cutting-edge research to find a cure for IS. This collaborative, milestone-driven project examined potential therapeutic pathways and biomarkers in order to improve treatment options and decrease lifelong disabilities that often result from IS. With additional resources we can build on the important work done by our preeminent investigators.

This year, as you consider your annual holiday giving, we hope you will consider CURE and its impact on kids like Mickie and the hundreds of thousands of other children with epilepsy.

Our work inspires and gives meaning to parents of children with IS. “CURE gives children their best chance,” Mickie’s mother, Kristie, says. “It offers hope for families with intractable epilepsies, and pulls all the parts together. CURE is a vital link in the chain that connects mothers like me to the leading-edge research that is pushing us closer to a cure.”

Your ongoing support will help ensure that the finest scientific minds continue working together to move us closer to our ultimate goal: no seizures, no side effects, and a cure for epilepsy. 

Mickie’s mother, Kristie Griess, considers Mickie’s journey the definition of a miracle and founded her own nonprofit – Mickie’s Miracles – aimed at creating awareness, education, and advocacy around pediatric epilepsy. She is also a passionate supporter of CURE.

Vigabatrin evaluated for focal seizures in tuberous sclerosis in recent study

A study, “Vigabatrin for focal seizures in tuberous sclerosis,” found that [1]:

Vigabatrin (VGB) is used for focal seizures in tuberous sclerosis (TS) and may be an effective therapy in patients who fail to respond adequately to other anti-seizure medications while awaiting definitive epilepsy surgery.

Vigabatrin is well-established as the first-line therapy for infantile spasms in association with tuberous sclerosis, but less is known about its role in focal seizures due to tuberous sclerosis.

[Researchers] retrospectively identified 22 patients with tuberous sclerosis who received Vigabatrin for focal seizures, starting Vigabatrin in June 1989 and continuing through the present time. Nineteen (86%) had a history of infantile spasms and all except the two oldest, born in 1986, received Vigabatrin for infantile spasms. Eleven of these individuals exhibited improvement in or resolution of infantile spasms. Sixteen out of 17 with infantile spasms remained on Vigabatrin to treat focal seizures.

The risk for vision loss due to photoreceptor toxicity continues to limit prolonged use.

Chicago’s HAMILTON Miguel Cervantes Debuts New Original Song ‘Til the Calm Comes

Miguel Cervantes, who plays Alexander Hamilton in Chicago’s HAMILTON, is releasing a new original song ‘Til the Calm Comes about his family, wife Kelly, and their personal journey with their baby daughter Adelaide’s struggle with epilepsy.

The song and music video will be debuted live at the 19th Annual Citizens United for Research in Epilepsy (CURE) Benefit in Chicago on May 15th, 2017, alongside the Misericordia Heartzingers Choir. The song will be available for purchase on iTunes, and all proceeds will be donated to CURE.

Miguel is raising funds for CURE on behalf of his one-year-old daughter Adelaide. Adelaide suffers from Infantile Spasms (IS), a rare childhood epilepsy syndrome that can have profoundly negative long-term consequences. Starting at 7 months, Adelaide began having dozens of seizures per day and, as a result, has severe developmental and cognitive delays.

The CURE benefit will also feature Miguel and actors from the Chicago cast of HAMILTON performing pop hits and selections from some of Broadway’s greatest shows. More than 1,200 supporters attended last year’s benefit to celebrate CURE’s impact and helped raise close to $2 million for research. The organization was founded by David and Susan Axelrod and a small group of parents of children with epilepsy who were frustrated with their inability to protect their children from seizures and the side effects of medications.

This year also culminates their successful campaign for My Shot at Epilepsy, a fundraising effort led by Miguel and Kelly Cervantes.  The My Shot at Epilepsy campaign raised over $75,000 and released a widely seen PSA and Rap Video from Miguel.

Hamilton Star Opens Up About Daughter’s Epilepsy – “My Shot at Epilepsy”

As covered by The Chicago Tribune, Miguel Cervantes—the lead in the Chicago cast of “Hamilton”—and his wife, Kelly, are opening up about their struggle with epilepsy, teaming up with CURE to raise funds to find a way to defeat epilepsy. Cervantes, who performs seven shows a week, has recorded a public service announcement about epilepsy and, along with fellow “Hamilton” cast members, is offering to go caroling with one set of raffle-winning donors, host another set of raffle winners backstage during a holiday performance of “Hamilton” and perform a private cabaret for a lucky charity auction winner with deep pockets (bidding starts at $25,000).

Read more: Click here to participate in the campaign, see the prizes and view the PSA