Global Genes Grant for H-ABC

The Foundation to Fight H-ABC is a proud recipient of the Continuity of Care RARE Patient Impact Grant, providing urgent financial aid to rare disease families in need. The grant was provided by Global Genes to help our H-ABC community during the covid-19 crisis.

As part of the Global Genes RARE Foundation Alliance, Fight H-ABC is committed to collaborating with other rare disease organizations and exchanging best practices to drive better outcomes for the rare disease community.

Global Genes is an international nonprofit organization that connects, empowers and inspires the rare disease community, with the ultimate goal of improving the lives of the more than 400 million rare disease patients around the world and their families. If you have a rare disease, contact Global Genes at +1-949-248-RARE.

PRESS RELEASE!

https://www.prnewswire.com/news-releases/foundation-to-fight-h-abc-university-of-massachusetts-medical-school-and-yale-university-initiate-gene-therapy-study-targeting-cure-for-rare-disease-301150610.html?tc=eml_cleartime

Foundation to Fight H-ABC, University of Massachusetts Medical School and Yale University Initiate Gene Therapy Study Targeting Cure for Rare Disease~

Martin's Story

A lot of people dream about a happy family, with children roaming around the house, laughing and turning everything upside down. It was our dream, as well, to give our daughter the chance of sharing life with a sibling, while enjoying more of her childhood with the closest of friends.

When Martin showed no interest or skill in moving beyond his closest proximity, we initially thought he was just the laid-back type. Little by little our questions and fears have started to pile up on our insides and we decided to seek medical advice. From that moment on, things happened quickly – or so it seems now when looking back. In a matter of 6 months, we went from the basic pediatric consult to the MRI and, ultimately, the all-encompassing genetic testing (the whole exome sequencing) that brought us to the most concrete and terrifying explanations of all.

Learning your child has a genetic syndrome that might hinder him from doing whatever he wishes in life – we all dread this. Learning this genetic syndrome is degenerative and that regress is a possibility no matter how much therapy and hard work he does – this was heartbreaking. Learning this is one of the ultra-rarest syndromes around the world, with less than 200 individuals currently diagnosed – this shed an ounce of hope in making us think we cannot judge a prognostic based on a number that is small. This is the silver lining we found. We started focusing on the unknowns and on the freedom of spirit the unknown has to offer. The past two years have been awfully long and terribly short. With several hours of daily therapies, Martin managed to progress both with motor skills and cognition – bringing us on the verge of exploding whenever he managed and continued to do something new. It was on several occasions we thought this is adrenaline-like. Every progress, albeit so small and coming so slowly, feeds us with the energy and determination to work and aim for more.

Nature, however, has its course, no matter how much we would like to be able to control it. On Martin’s good days I am confident we will pull it through. On his modest days, we realize he needs a treatment, or a cure. He needs to have this addressed in a scientific way – more than us, his parents, could offer. In this respect, we are so thankful we found other families sharing a similar journey. We are a group inspired by the same vision and fighting for the same goal – push the research through and be able, in a couple of years from now, to provide our children a real chance to a good life.

We will be the happy family we are dreaming of. I am confident.

-Martin's Mother

PENN PLAZA NYC!

Very excited to have been featured all day on July 23, thanks to our friends at Adquick

How Covid-19 Impacted Us

For a child with a serious neurological condition like H-abc, inactivity is the worst situation even under normal circumstances. When COVID-19 evolved, here is how it impacted our family and other families like ours living with H-abc.

Initial Impact

We had to make a decision before anyone else, to keep our child home from school and other activities. We know other parents were struggling with this decision, but for a child with a condition like H-abc, exposure to viruses is very dangerous. Due to the lack of general inactivity and history with complications tied to respiratory conditions, the kids immune system are already compromised. We were very afraid to go out to the store, for fear of bringing the virus home. We ordered all of our food on-line for delivery. We used bleach to clean anything we came in contact with. Our meds were sent in the mail! We cut off physical contact with everyone, as did most people.

Therapy

We became Occupational and Physical Therapy experts! Luckily, we had equipment at home to use. We met and continue to meet weekly with therapists on Zoom and learned how to provide the much needed therapies to keep Elouise strong and active. Every day we apply these therapies and she is probably now in the best shape ever! We are lucky to have a heated hydro pool donated by Make A Wish! It was installed just before the quarantine hit. We used it almost daily, even in the colder months of March and April. It was a life safer, not only physically, but a great outlet and diversion from the monotony.

Family and Friendships

For kids with neurological conditions like H-abc, their means of communication with others are hugs and smiles. This all went away when we were quarantined. Elouise loves to hug, its her way of expressing her feelings as her verbal abilities have diminished over time. It was very difficult to be cut off from her school friends and church friends and family. Even under normal circumstances, developing relationships for kids with neurological conditions are difficult given their mobility and speech challenges. During COVID, the complete void of any interactions with her network of people was and is difficult. However, Elouise spends much of her time watching her shows, and following her Teen idols and calling her family and friends!

School

We as parents, very quickly became experts on how to access the online classrooms, how to do math, write essays and generally revisit 8th Grade Middle School! Kids like Elouise need one on one assistance at school. She is unable to do this alone. So, with much challenge, we figured out how to navigate it all, set up a schedule, met with her teachers and peer remotely, worked on homework, and managed to graduate from 8th Grade!!

Summer

Camps are cancelled, pools are opening but with restrictions. Our camp for kids with disabilities couldn’t accommodate us due to the close hands on assistance that is needed and fact all activities are restricted to the outside, in the heat, wearing a mask. This is very difficult for a child like Elouise so we couldn’t attend and in fact, the entire program was cancelled.

The New Normal

As the disease progresses for children with H-abc, we are always learning to adjust to a new normal. Ten years ago our normal was a child who could walk, run, write, play, and speak just like any other kid. Over time we have adjusted to the progression of this disease, and today Elouise is in a wheelchair and using a spelling board to communicate. But she is healthy and happy. As others across the globe are adjusting to the new normal post Covid, we will need to figure out how to live with social distancing, and its very unclear how that looks for us. Some parents are not letting their kids go back to school until a vaccine is available, that could be over a year. Consider the therapies which involve close interaction with others indoors, all of which increases the risk of transmission of viruses. With all the challenges kids with neurological conditions face, this creates more complexity.

Our Outlook

Its hard to say what the next year will look like, and given concerns with the virus possibly surfacing again at elevated levels, its even more unclear. However, as we did before the virus and as we continue to do moving forward, we will live each day, day by day, to its fullest with hope and faith!

Understanding the TUBB4A Gene: What It Is and How It Relates to H-ABC

Genetic disorders such as hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) can be tough to grasp. This is largely because research on rare diseases is lacking. At the Foundation to Fight H-ABC, one of our goals is to educate affected families and interested advocates. That’s why we wanted to take this opportunity to provide an overview of the TUBB4A gene, looking at… 

• What this gene actually is

• When it was discovered

• What causes a mutation in the gene

• How the gene relates to H-ABC

• What research is being done

By learning about this gene, you can gain a deeper understanding of the role it plays in related disorders such as H-ABC.

Let’s get started…

What Is TUBB4A?

TUBB4A, which stands for tubulin beta-4a, is one of the many genes that code for proteins. This gene provides instructions for making beta-tubulin (β-tubulin)—a protein found primarily in the brain, specifically the basal ganglia and the cerebellum. β-tubulin belongs to a family of proteins that form and organize structures known as microtubules.  

A Brief Introduction to Microtubules

As mentioned above, β-tubulin is one of two proteins that make up microtubules. The other protein is alpha-tubulin (α-tubulin), which is produced from the TUBA1A gene.

Here’s a simplified explanation of how microtubules are created:

1. The β-tubulin and α-tubulin proteins join to form a dimer.

2. These dimers then form polymers—long, repeating chains of molecules.

3. The polymers are then put into a sheet and rolled up to create a tube.

Essentially, microtubules are rigid, hollow cylinders composed of tubulin. These microtubules are a key component of the cytoskeleton, which is a network of filaments that exists in the cytoplasm of eukaryotic cells.

What do microtubules do?

The main purpose of microtubules is to support and give shape to the cell. However, they serve a few other important functions. For example, as the brain develops, microtubules help transport nerve cells to the right location. This process is known as neuronal migration.

When Was the Gene Discovered?

To give you a brief history, the gene was identified by researchers back in 1984 and originally designated as 5-beta. Since then, a lot of information about this gene has come to light…

In 2010, a group identified eight major β-tubulins, including TUBB4A, which they referred to as TUBB4. Then, in 2013, another group examined the presence of this gene in the brain, discovering the highest expression to be in the cerebellum; this part of the brain plays an important role in muscle control and movement. That same year, researchers performed gene mapping and traced the gene to chromosome 19p13.3.

What Causes a TUBB4A Gene Mutation?

In most cases, a change in the TUBB4A gene is a random mutation. Typically, neither parent is a carrier, which means the chances of having multiple children with the mutation is low. However, if a parent does carry the mutation in some cells (usually due to mosaicism, when a person has two or more genetically different sets of cells), they could pass it along to their children.

How Does This Gene Relate to H-ABC?

The connection between this gene and H-ABC is simple: A mutation in this gene is what causes the disorder.

H-ABC is a type of TUBB4A-related leukodystrophy, a disease that affects the white matter of the brain. The 52 conditions labeled as leukodystrophies disrupt the growth or maintenance of the myelin sheath. This protective layer insulates nerve cells and allows messages to be transmitted between cells. In the case of H-ABC, hypomyelination occurs. This means the body doesn’t produce myelin at normal levels, so the process of forming that protective layer can’t be completed. Additionally, the condition reduces the size and function of the basal ganglia and cerebellum. However, it’s worth noting that not all individuals with the gene defect have every aspect of H-ABC; some have hypomyelination but not atrophy of the parts of the brain mentioned above.

When there’s a mutation in this gene, it alters single protein building blocks—also known as amino acids—in the β-tubulin. In most cases, H-ABC presents when the mutation results in the replacement of one amino acid with another. An example would be the replacement of aspartate with asparagine. It’s believed that these kinds of mutations change the structure of β-tubulin, which then affects the formation or structural integrity of the microtubules it helps form.

How does it all tie together?

At this time, it’s still unclear how such genetic changes cause the symptoms of TUBB4A-related leukodystrophy, with some examples including…

• Seizures

• Deafness

• Involuntary movements

• Poor coordination

• Speech problems

• Difficulty eating

• Loss of balance

• Attention problems

However, researchers suspect that problems with microtubules affect neuronal migration or the transport of key substances within neurons. This may lead to the dysfunction and loss of these cells in the brain—the white matter in particular.  

What Research Is Being Done on TUBB4A and Leukodystrophies Such as H-ABC?

As stated before, researchers have uncovered quite a bit about the TUBB4A gene. Because of their efforts, we know what the gene does, where it’s located, and how it can affect the body when a mutation is present.

Now we need to figure out how to treat and prevent the diseases that result from its mutation. This is what researchers are working on now. The good news is doctors and scientists have already made significant headway by…

• Completing cellular-level research of H-ABC

• Researching the biological makeup of this disorder

• Developing a natural history study

Although genetic disorders such as H-ABC aren’t easy to fight, gene therapy has proven itself to be a promising method of curing cellular-level diseases. This can be done in one of three ways:

1. Reduce the expected toxicity to cells from the mutated tubulin by using an approach that captures RNA before it becomes proteins (antisense oligos or ASOs). The advantage of this type of approach is a relatively well-established treatment for certain neurodegenerative conditions.

2. Out-compete the mutant tubulin through overexpression of wild type (i.e., correct) TUBB4A in the cell via adeno-associated virus (AAV). This is a specific virus engineered to deliver the correct mutation to targeted cells.

3. Correct the mistake in the tubulin gene through a highly novel gene-editing approach that can correct spelling mistakes in genes (using CRISPR to correct the mutation at the DNA level). This approach is still very new.

Once the doctors and scientists involved in this research determine the best approach for gene therapy, we can proceed to the next step—getting FDA approval to conduct a clinical trial.  

However, it’s important to note that clinical research can’t move forward without proper funding. That’s why we need to generate greater awareness of H-ABC and other leukodystrophies caused by a TUBB4A mutation.

Takeaway

Genetic disorders such as H-ABC can be hard to understand at first. That’s why it helps to get some background information. Once you trace the condition back to its source, you begin to see how the tiniest defect can have a major impact. In this case, you can see how a defective TUBB4A gene can lead to a debilitating disease like H-ABC.

Take this opportunity to learn more about the gene responsible for H-ABC. And be sure to share this information with others. By giving related leukodystrophies such as H-ABC the attention they deserve, we can help experts perform additional research so they can find a cure.   

3 Things I Want People to Know about Kids with Rare Diseases

Kids with rare diseases (and their families) just want to receive the same kindness, respect, and consideration as anyone else.

With that in mind, here are 3 important things I want people to know and think about…

1) Kids with Rare Diseases Want to Have Friends.

Our kids want to have friends just like yours do! Encourage your child to reach out to kids with rare diseases such as H-ABC in a manner that’s natural—not forced or because it’s the right thing to do.

Children like Elouise can be great pals to other kids, as long as other kids are willing to adjust to certain limitations. There is so much they can do together once they figure out how to communicate!

Many times, I’ve seen parents use us as a means to teach their kids how to give back to those less fortunate. I understand what they’re trying to do. However, if this isn’t done in a natural way, it’s not sincere and it makes it difficult to foster a natural relationship. And, frankly, my child isn’t a teaching exercise. She’s a wonderful, happy little girl who loves people. 

2) These Children (and Their Families) Want to Be Included.

Children with rare diseases want to be included, and the same goes for their families. So, please don’t exclude us. Perhaps make that extra effort to include us, even if we turn you down initially. All too often, we are stereotyped. This is likely done unintentionally, but we are.

As the mother of a child with a rare disease, I tend to stay away from others when it comes to social activities. This is only because I don’t fit the mold and my child doesn’t fit in, much less have the ability to participate.

Most people are—on the surface—kind, but unless we are extroverted, parents affected by rare disease typically shy away from others and find solace within our own circles. It’s simply because we are better understood by those who are experiencing the same things or at least familiar with our situation. 

Kids with H-ABC vary in terms of their symptoms and abilities. Some have limited obvious symptoms (until they have to move or speak), whereas others have symptoms that are much more apparent.

When in doubt, imagine if your child had a neurological condition. How would you want to be treated?

3) Those Affected by Rare Disease Should Be Accepted and Treated Like Anyone Else.

When you meet kids with rare diseases and their parents or caregivers out and about, please don’t stare. 

Initially, I would get really annoyed when people would stare or turn around to look, knowing a child is disabled and curious to see just how afflicted they are. I’ve even experienced someone referring to a child with a neurological condition as “it.”  

Those of us affected by rare disease want nothing more than to be accepted and treated like anyone else.

Eventually, I came to realize that people just can’t help it. So, instead of getting upset, I smile and say, “Hello, meet Elouise.”

How I’ve Worked to Give My Daughter a Happy Childhood Despite Her Condition

At this point, my focus is on giving my daughter, Elouise, a happy childhood and letting her experience as much as she can in life, which is very difficult due to her lack of mobility.

Making Memories

Recently, we took her skiing using an adaptive ski service, which took her up and down the slopes in a special chair with three assistants. She loved it.

We set up a track in our home to which she is attached via a secure vest and is able to walk with her dog and dance with us!

We try to go to different places so she can see the beach, the mountains, and more. Additionally, she loves animals, so we try to do as much as we can around them.

The Challenges We Face in Giving Our Daughter a Happy Childhood

Friendships

Although most people are kind, Elouise has no close friends who come over and spend time, which is very sad because she loves people. Even more difficult is how she and, to a degree, we as her parents are excluded. We know it’s not done intentionally. It’s just the way it is.

As an example, Elouise can’t do sleepovers at someone’s house; she just needs too much care and oversight. We’ve done a few at our house in earlier years, but after a while, the kids lose interest given her inability to do most everything. At age 14, this is even harder, as friendships are a key part of having a happy childhood.

This saddens me more than anything else does. Without her family, she has very little.

Future Considerations

We also have to make plans for extended family to be there for her if something happens to us, and that is a lot to ask of anyone.

The last thing we would ever want for her is to be in an institution, which is a factor every parent of a disabled child has to take into consideration and plan for.

Living in the Moment & Providing Protection

I try not to think about what Elouise is missing; I just try to enjoy the moment. She is a happy child and that makes things much easier.

Elouise is cognitively at an age-appropriate level, although her exposure to things kids her age see is entirely different given her lack of emotional ability to process or understand certain things. I don’t know to what extent she grasps her situation other than I don’t think she knows any different.

Her memories from her younger years when she was more mobile are limited.

I never see her show resentment or anger toward her situation. She is extraordinarily unaffected in this respect, which is a blessing and helps in ensuring she has a happy childhood.

In some respects, given her very limited life experiences, she is shielded by many of the trials, difficulties, and dangers that kids her age experience these days. I don’t know if that’s a blessing, but her life is surrounded by positive things and she is very protected from the world. This is largely due to her inability to make any decisions for herself given her level of maturity, lack of physical capabilities, and the constant adult supervision needed to take care of her.

We are very mindful of making sure she is surrounded by kind and trustworthy people, and frankly avoid situations or exposure to any unnatural or negative influences currently rampant in society today. As such, our life has become somewhat reclusive, hers even more so, but I don’t think there is an alternative. This may be common to many kids and families affected by similar neurological conditions, not just H-ABC.

5 Reasons the Foundation to Fight H-ABC Is a Great Cause to Support

As someone who is passionate about helping others and making a difference in the world (especially during challenging times), you’re always on the lookout for another great cause to support. Having learned a little bit about the struggles that those affected by H-ABC go through every day, it’s likely you’re interested in getting involved. However, you want to be sure that your contribution—whether it’s time, money, or both—is going to make a positive impact.

We want to show you how it can.

Here are 5 reasons why this cause is one worth supporting and what you can look forward to in aiding our organization’s efforts…

1) You Can Play a Role in Funding Important Medical Research.

One of the benefits of joining us in the fight against H-ABC is that you’ll be able to contribute to the advancement of medical science. Our primary aim is to assist doctors and scientists in their quest for a cure, which requires a significant amount of clinical research. However, what you may not know is that this research has the potential to help people suffering from other conditions in the future.

When those in the medical field have the funding they need to carry on their work, they’re able to find new methods of detection, diagnosis, treatment, and prevention. But the possible applications of their findings can extend far beyond the disease they’re studying. These findings can help in treating conditions that are similar.

Further, it’s not uncommon for breakthrough medical discoveries to be made on accident… Several vaccines, diagnostic tests, and treatments have been developed while studying something completely different.     

Ultimately, every discovery that’s made in an attempt to cure H-ABC is one that can be applied elsewhere, saving even more lives in the process.     

Whether you donate yourself or encourage others to do so, you’ll be playing an important role in furthering research for the good of all! 

2) You Can Assist in Raising Awareness of a Widely Unknown Disease.

By getting involved with the Foundation to Fight H-ABC in any capacity, you can also assist us in extending our reach, putting a spotlight on a disease that’s still widely unknown. Although the number of cases is on the rise, most people (including many health-care professionals) don’t know it even exists. Through our efforts and those of our supporters, we’re working to change this so the children who suffer from the disease don’t go overlooked.

Sadly, rare diseases such as H-ABC simply don’t get the attention and funding they deserve. As a result, families struggle to find doctors who are knowledgeable and treatments that can combat the symptoms. Although this isn’t fair, as rare diseases deserve just as much scrutiny, it is the current reality. But the good news is you can bring us one step closer to a new reality—one in which conditions aren’t ignored just because they don’t afflict as many people as others do.

It’s something we’ve said many times before, but it’s a message that bears repeating: No act of kindness is too small in supporting the fight against H-ABC.

There are various ways to take action and help raise awareness, making this a great cause to support.  

3) You Can Help Find a Cure for a Debilitating Condition.

Another reason ours is a great cause to support is the fact that doing so allows you to help find a cure for a disabling disorder—one that slowly robs children of their ability to walk, talk, eat, dress, and bathe without assistance.

The symptoms of H-ABC vary from one child to the next, but some examples include the following:

• Speech problems

• Difficulty eating

• Poor coordination

• Seizures

• Attention issues

• Deafness

• Learning difficulties

Further, those with H-ABC are particularly vulnerable to viruses, including COVID-19. As their bodies are already dealing with one health condition, they’re unable to fight off acute infections. Complications can arise and an afflicted individual could end up in critical condition. 

Worst of all, the life expectancy for those with H-ABC is shortened. As the disease progresses, body functions continue to decline until it’s too late…

By getting involved in the fight against H-ABC through donating or volunteering, you can help fuel research for a cure and put an end to its progression.

4) You Can Feel Confident You’re Supporting a Trustworthy 501(c)(3) Organization.  

An additional benefit to joining us is that you can rest assured any donation you make is going exactly where it should. As a certified 501(c)(3) organization, our foundation is fully authorized and recognized by the IRS as a nonprofit charity. This means you can have peace of mind knowing you’re giving to a legitimate nonprofit.

All proceeds go directly to efforts for curing H-ABC. The donations we receive are used for several purposes, such as funding the genetic research and related costs as well as establishing facilities where doctors can study patient data—all of which is part of the process for finding a cure.

Further, getting involved with the Foundation to Fight H-ABC allows you to receive a tax deduction for charitable giving. Chances are you’re not looking to donate for any sort of monetary gain; you’re looking to make a difference in the lives of others. However, it is a nice bonus that you can claim your contribution as a deduction when tax season rolls around.

However you choose to help, you can trust that you’ve chosen a great cause to support!

5) You Can Be a Hero to a Child (and Family) Affected by H-ABC.

Perhaps one of the most compelling reasons to join the fight against H-ABC is that it offers the opportunity to be a hero to those affected by the disease. Given the current goings-on, it’s a role that you’re likely eager to take on.   

As of today, fewer than 200 cases of H-ABC have been identified, but that number is on the rise. When families are given the diagnosis, they have a hard time adjusting to their new normal. They need support. They need education. But most of all, they need hope for a cure.  

When you decide to support our foundation, you provide families with all of those things and more. You demonstrate your compassion, kindness, and empathy. You show that you’re committed to fighting alongside them. 

In short, you become a hero.

In Summary – The Foundation to Fight H-ABC Is a Great Cause to Support

As you’ve learned, there are several benefits to getting involved with the Foundation to Fight H-ABC. We’re proud of what we’re doing and what we’ve accomplished so far. Moreover, we’re grateful that caring people like you have decided to join our fight.  

If you believe ours is a great cause to support and you want to aid our efforts, take action today! 

Coping with a Sick Child: Where I Find Hope on Dark Days

From an outside perspective, it would seem that our situation in terms of coping with a sick child is very difficult. However, the truth is that this didn’t happen overnight. Like anything else that is handed to you in life, there is a process you go through:

• First, you react to the issue.

• Then, you adjust your life accordingly.

• Then, a new normal ensues.

Focusing on What Really Matters

Over the years, we have adjusted our life to meet our child’s needs and adapt to her condition. Our priorities used to be our work, our social life, our athletic activities, our family, and our church. Now, however, our top priority and focus is mainly Elouise—maintaining her health, keeping her active, and showing her everything we can in life given her limitations.  

For me that is my mission: to keep my daughter healthy and happy. 

Coping with a Sick Child during Hard Times

When times have been tough, it has usually been tied to the progression of her condition—specifically when surgery has been required.

Elouise has done very well in each case. Outside of her condition, she is very healthy overall. Other children have more chronic internal or neurological issues that, on an ongoing basis, would frankly be even more difficult to handle.

As parents of kids with H-ABC, we have come together in support of one another and have provided each other with amazing resources to help. We’re able to relate with each other, as we understand the struggles that go along with coping with a sick child. Moreover, we take every opportunity to learn from one another and share information.

At this point, we as the parents probably know more about this condition than the medical professionals do.

Taking on an Important Mission

In between our focus on Elouise, we are working on trying to figure out ways to expand our foundation’s presence so we can help find a cure, get more attention, and gain national recognition. In many ways, this endeavor is somewhat therapeutic. 

I have found there to be so much kindness in this world—in many cases, from people we don’t even know! The number of people who have come forward wanting to help in some way is surprising and truly inspirational. 

Holding on to Hope

Lastly, coping with a sick child requires hope. And my hope comes from a higher power. One thing we have come to learn is that you just don’t know what might happen, who might come forward, and how that could help.

We cannot do that without getting the word out and drawing attention to the disease. 

Don’t get me wrong… There are days that are dark, and not one day goes by without me wondering what is in store for Elouise and, in turn, us. But if you allow that to get the better of you, then you are losing sight of the good things that can happen.

Without your faith, then if you give up, you have no hope!