The first sign of Col4A1 was at our 20-week ultrasound. They had identified his front brain ventricles were slightly more dilated than the norm. It was just one or two points higher, so we didn't think much of it. When he stopped growing and took him at 37 weeks, identified the brain bleed, cataracts, and VSD we knew something wasn't right and got genetic testing done soon after.

The disorder has a bit of a snowball effect. Because of the
abnormal blood vessels in the brain, he had a stroke in utero that damaged his brain and caused the infantile spasms. He was born with cataracts and is only able to see light at this point.  He has a muscle disease (myopathy) that causes muscle weakness, and muscle spasms creating much pain for Brooks. The muscle disease paired with the brain damage/brain structure abnormalities prevent Brooks from developing. Brooks is still at an infant level for development. Brooks also has kidney abnormalities (renal pathology) causing chronic UTIs. In addition, Brooks has lung (pulmonary) abnormalities which weakens his immune system making him sick often and could take months to recover from a simple cold that a normal kid shakes off in a couple days. Brooks has 100+ seizures a day causing constant chaos in his brain. All of these complications causes lots of doctor visits and on 9/8/2021 will be his 8th surgery and the brain surgery will be #9.

It’s emotionally debilitating for us. Sleep is a struggle. Not only from constant worry but it’s not uncommon for Brooks to wake multiple times a night because of his seizures. Brooks still sleeps in our room because he is at an increased risk of additional strokes and has multiple seizures a night. Even simple things like going out as a family poses challenges as Brooks doesn’t tolerate his car seat and screams at the top of his lungs for entire car rides. He also can't hold his head up so holding a 25lbs babe that can't support himself is harder. You can't just plop him in a grocery cart and get to shopping. Our new norm has definitely changed but of all these new hurdles there is nothing more frustrating than being completely helpless in your pursuit for health for your child. 

Time and time again we have been told, there is nothing more we can do or we just need to ride it out. Unfortunately we do not have time on our side and we refuse to take no as an answer. 

Brooks is the strongest person we know. He has endured
more in his short life than most do in a lifetime. His smiles and little
giggles are seriously the best thing in this world and will melt anyone’s
heart and we will continue advocating and fighting for our sweet boy until the end of time turning over every friggin' rock there is!

Dustin and I spend hours a week researching clinical trials, innovative treatments and new therapies that could possibly help Brooks. When first reading about this project it provided us with a tremendous amount of hope that we had lost. We had learned of gene therapy from our friends who told us about the documentary unnatural selection. But never in a million years thought a project focused around Col4A1 would occur in this lifetime since it impacts such few people. This project is a MIRACLE and will be life changing for Brooks. 

After we originally identified the project, we immediately emailed Dr. Arshad Majid asking questions about the project and how we could help. Dr. Arshad was was eager to share the details as his team had treated a Col4A1 patient and saw first-hand how terrible the disorder is and was anxious to find a solution to help. Dr. Arshad's professional mission is to develop new therapies for patients afflicted with neurological diseases, especially cerebrovascular diseases. We would soon learn that Dr. Arshad conducted his Fellowship training in Stroke Research at Washington University in St. Louis. What are the chances that the doctor leading this project in the UK would have spent his fellowship years here in St. Louis?

Coincidence, I think not. Miracles happen everyday and we look forward to watching our miracle's bright future.

Gene Therapy for COL4A1-related disorders, The next generation of medicine

Gene therapies represent tremendous potential for patients living with severe and hard to treat genetic diseases. Our ambition is to lead research into a new gene therapy approach for COL4A1. However, funding for research into rare diseases is still a challenge. In collaboration with families impacted by this condition, we are raising funds to support this pioneering project. Can you help us?

What is COL4A1?

COL4A1-related disorders are a group of rare genetic conditions that
are characterized by fragile blood vessels. The conditions in this
group have a range of manifestations including abnormalities of the brain, eye, kidney and blood vessels. The signs and symptoms can become apparent at almost any age from before birth to old age.

One of the biggest challenges for this disorder, and for rare diseases generally, is that there are no standardized treatment protocols or guidelines for affected individuals. Funding is also a major challenge; because rare diseases affect a small number of people relative to cancer or cardiovascular disease for example, they are often considered lower priorities when it comes to allocating research funding.

Gene therapy the future for treating rare diseases

Although individually uncommon, collectively rare diseases affect a huge number of people - roughly 350-400 million people worldwide, or between 5-10% of the worlds population. Most rare diseases affect children and many are fatal or severely disabling. This great unmet need makes it imperative that we find new treatments to help the many patients and families who are in search of better treatments.

However, there is great hope. Medicine is evolving and innovations in gene therapies show outstanding clinical potential for treating rare genetic conditions such as COL4A1-realted diseases. Gene therapy is the introduction of a new gene to a patients cell to replace, silence or manipulate the faulty one. The goal of gene therapy is to restore normal function in affected tissues or cells, potentially
enabling a patient to live without the need for ongoing treatments. To achieve this, a custom-made virus vector is used to deliver the genetic material into patients cells.

Our ambition is to embark on a new project to silence the abnormal COL4A1 gene using a technique called shRNA delivered to the cells using a virus or other means. We believe that silencing the abnormal COL4A1 gene could lead to the manufacture of normal collagen in cells and will improve symptoms of the condition.

Why Sheffield?

The UK has a world-class genetics research base and the University of Sheffield is a leading player. We are the first site in the UK delivering both stem cell transplantation for multiple sclerosis and genetic therapies for Amyotrophic Lateral Sclerosis (ALS) clinical trials. We are renowned for our translational neuroscience research through the Sheffield Institute for Translational Neuroscience (SITraN) and the Neuroscience Research Institute. Sheffield is home to the only National Institute for Health Research (NIHR) funded Biomedical Research Centre in the UK a collaboration between the University and
the Sheffield Teaching Hospitals NHS Foundation Trust, which is one of the UKs largest and most successful hospitals within the UK National Health Service (NHS).

A new Gene Therapy Innovation and Manufacturing Centre (GTIMC) is currently being built in Sheffield and is part of a pioneering network of Gene Therapy Innovation Hubs in the UK dedicated to the clinical development of genetic medicines. The GTIMC will manufacture the viral vectors required for gene therapeutics and provide the critical expertise to swiftly move potential new treatments through early phase clinical trials to commercialisation, helping the most innovative research to reach patients.

At Sheffield, we have all the necessary expertise and the facilities to carry out this research in preclinical models of the disease. Once that part of the project is complete and if successful, we will be in a unique position to start clinical testing, thanks to the GTIMC, which can manufacture the gene therapy treatment in Sheffield.

How can you help?

All funding received will support an outstanding Post-Doctoral Researcher for three years to lead on this research.

We invite you to be a part of this vision, which could influence the future treatment of COL4A1-related disorders and the health outcomes for people affected by them.

Should you want to donate more than $500 we encourage you to donate directly through https://www.sheffield.ac.uk/giving/usa

Thank you for your support!

If you have any questions please contact me at bcmhtc@gmail.com or 314-616-1765.