Rare Disease: An Overview of STXBP1

STXBP1 is a gene that encodes a specific protein called MUNC18-1 which is essential for synaptic transmission¹. The MUNC18-1 protein is a key protein that helps organize the SNARE-complex which is responsible for mediating vesicle fusion with the cell membrane or other vesicles². A mutation in the STXBP1 gene can result in impairment of psychomotor and neurodevelopmental capabilities¹. Phenotypically, individuals with STXBP1 gene mutation and disruption of SNARE-complex formation of MUNC-18-1 protein will present with intellectual disability, movement disorders, and epilepsy³.

Severe early onset epileptic encephalopathies, such as Ohtahara syndrome, West syndrome, and Dravet syndrome are associated with mutations in the MUNC18-1/STXBP1⁵. These encephalopathies are often fatal and are categorized by severe intellectual disability and cerebral dysfunction. Most encephalopathies include incessant epileptic activity that causes decline in cognitive, sensory and/or motor function⁵.

STXBP1-related disorders are rare, only 750 cases of individuals diagnosed with an STXBP1 disorder are known worldwide⁴. The incidence of STXBP1 disorder ranges between 3.3-3.8 per 100,000 births and impacts families from various ethnic backgrounds that spans North America, South America, Europe, Africa, and Asia⁴.

STXBP1 Summit 2022

ClinChoice had the pleasure of being a Champion Sponsor at the STXBP1 Summit that took place in August of this year. The STXBP1 Summit was an opportunity to learn firsthand from family members who are caregivers of this delicate patient population. The conference offered a bridge between all key stakeholders that are involved in research surrounding STXBP1. The event also provided a unique environment to connect with patients, investigators, researchers, sponsors, and families. The silos that are often found in research were non-existent and everyone was able to freely communicate. This occasion fostered a wealth of information and perspectives to be shared amongst each key stakeholder.

At ClinChoice, the experiences as a collective in the research realm have broadened our understanding of research at all levels. Areas of profound recognition include the importance of involvement from rare disease foundations, listening to parents and advocates on how to lessen the burden of participating in a clinical trial, as well as ways to improve trust and increase patient participation and retention. Having these events is important for intrapersonal and interpersonal development and cultivates a community of trust between all key stakeholders participating in research.

Current studies and research in STXBP1

STXBP1 studies are still in the early stages of development. Currently there are no approved cures for this disorder. The available therapeutic strategies are centered around treating the symptoms of the disorder, mainly epilepsy⁵. While some children with STXBP1-disorder seizure episodes dissipates approximately 40% of children still have epileptic episodes⁶.

The only FDA approved drug that is being used to determine its effects on STXBP1 disorder symptoms is known as Glycerol phenylbutyrate⁷. This drug is used to lower high levels of ammonia in the blood caused by urea cycle disorders⁷. Although glycerol phenylbutyrate is an FDA approved drug it is not approved for STXBP1 disorder indication. Nonetheless studies have shown some reverse to the deficits caused by mutations in the MUNC18-1/STXBP1 in mice models ⁷.

There are currently clinical trials testing glycerol phenylbutyrate in children to ascertain whether they can observe the same or similar improvements in deficits caused by STXBP1 mutation⁸. In addition to this drug study there are other studies coming in the pipeline which were highlighted at the SXTBP1 Summit such as natural history studies, further exploration in mice models, zebrafish models, and gene therapy research. Researchers, sponsors, and investigators are taking various approaches to furthering the science of STXBP1 that can potentially result in more treatment options and lead to a cure for this disease.

Conclusion

STXBP1 is a rare disease that phenotypically can present like many neurodevelopmental disorders. The treatments available are more focused on alleviating the symptoms of the disease and are highly centered around seizures. Doctors, sponsors, and researchers from around the world are working diligently to find out more about the STXBP1 disorder. The STXBP1 Summit acts as a vehicle where all stakeholders can share ideas, foster relationships, and cultivate a community of strength, knowledge, and compassion.

At ClinChoice, we are working together with these stakeholders to advance science to improve the quality of life of the individuals and families impacted by STXBP1 disorder.

The ClinChoice approach to rare disease clinical trials

Rare diseases present significant challenges to ongoing studies due to unclear natural history and small sample sizes. To lessen the complications brought by these factors, ClinChoice routinely provides tests combining multiple endpoints. By implementing global tests such as the Wilcoxon Rank Sum test or the O’Brien Test, we are able to supplement the separate analyses for individual endpoints. Providing statistics and programming services for a multitude of rare disease drugs in the past, ClinChoice has extensive experience in rare diseases and strategies for addressing small and widely dispersed sets of patients. This enables us to quickly develop efficient custom processes that can significantly speed up a product’s time to market and ultimately provides safe solutions to those affected.

Talk with a specialist today to discuss how ClinChoice can customize solutions for your rare disease clinical trial.

About the Author

Dr. Tia Warrick is responsible for the project management aspect of clinical trials. She works with sponsors and cross functionally within the ClinChoice team to ensure that all levels of a clinical study are being conducted in accordance with the protocol, ICH and GCP guidelines. In addition, Dr. Warrick acts as a conduit between sponsor, ClinChoice, and site level communications on a global level.

About Us:

ClinChoice is a leading global Contract Research Organization (CRO), with over 3400 clinical research professionals across North America, Asia, and Europe. For more than 27 years, ClinChoice has been providing high-quality contract research services to pharmaceutical, biotechnology, medical device, and consumer products clients, encompassing a broad range of services and therapeutic areas. ClinChoice offers cutting-edge, full-service solutions for Clinical Trials, Regulatory Affairs, Medical Device Safety, Toxicology, and Medical Affairs.

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