Fucose Session with Dr. Rodrigo Starosta

Hello and welcome to Science with Sandra!

For this special edition, I’m sharing a summary of the meeting with Dr. Rodrigo Starosta, a medical geneticist at Oregon Health & Science University (OHSU) who specializes in rare metabolic disorders and will be conducting the upcoming fucose clinical trial in our community.

The purpose of the meeting was to share important information about the clinical trial. Dr. Starosta provided background on his professional experience and expertise. He is a specialist in Congenital Disorders of Glycosylation (CDG), including fucosylation disorders (the CDG-F). Patients with these CDG-F conditions are unable to properly attach fucose to molecules that require it for correct structure and function. Treatment for this disorder involves fucose and mannose supplementation. His experience treating CDG-F patients with fucose and mannose (which acts a precursor to fucose in some, but not all, cases) inspired his desire to help the GLUT1 Deficiency community by conducting this upcoming trial.

Many of us are now familiar with fucose, but as a reminder, fucose is a monosaccharide found in a wide range of organisms, typically in small quantities. L-Fucose (the active form of fucose) is a dietary sugar that plays important roles in cellular biology.

What is the evidence that fucose could help GLUT1 Deficiency patients?

Fucose is an important metabolite in the cerebellum, basal ganglia, and cerebral cortex:

• The cerebellum controls coordination and fine motor movements; when affected, patients may experience ataxia and dysarthria.
  
• The basal ganglia help regulate muscle movement; when affected, dystonia and dyskinesia can occur.
  
• The cerebral cortex is responsible for sensory and motor processing as well as cognitive functions. Seizures, developmental delays, and cognitive issues often arise when the cortex is affected.
  

Many individuals in the GLUT1 Deficiency community experience motor difficulties, seizures, and cognitive challenges, symptoms that fucose may potentially improve.

Additionally, there has been a case of a young patient with GLUT1 Deficiency who did not respond to the ketogenic diet but experienced significant improvements in motor function, development, communication, and blood test results after receiving fucose treatment.

Animal studies have also shown that mice with GLUT1 Deficiency treated with fucose demonstrated improvements in motor function and brain metabolites, for now, these are preliminary results by other researchers, and they have not been published yet as scientific articles, although the data has been presented at scientific conferences.

Moreover, patients with CDG-F who present symptoms similar to those seen in GLUT1 Deficiency have shown notable symptom improvement when treated with fucose.

Potential Side Effects

Dr. Starosta also shared possible side effects that participants might experience, including:

• Stomach issues at the beginning of the trial
  
• Potential hemolysis (a type of anemia), which has been observed in a small number of CDG patients who lack a specific protein on red blood cells, which a very rare condition.

It is important to say that there may be other side effects from fucose supplementation that are not yet known or that are specific to GLUT1 Deficiency, which is why doing a trial in a standardized manner is important.

Study Design and Aims

The goal of this upcoming clinical trial is to evaluate the safety and effectiveness of fucose in patients with GLUT1 Deficiency.

This is a Phase II clinical trial, designed to assess safety and preliminary efficacy. The primary outcome will be ataxia, while secondary outcomes include migraines, fatigue, seizures, dyskinesia, and quality of life. The results will help determine whether ataxia is an appropriate primary outcome for a future Phase III trial.

This is a crossover, double-blind study, meaning each participant will receive both fucose and placebo treatments in random order, and neither the participants nor the researchers will know which treatment is being administered at any given time.

Research Participation

Inclusion Criteria:

Individuals eligible to participate in this study must meet all the following inclusion criteria:

1. Age over 18 years old
2. Confirmed diagnosis of GLUT1 Deficiency, including at least 2 out of the following 3: molecular genetic testing showing a pathogenic or likely pathogenic variant in SLC2A1; documented hypoglycorrhachia with a CSF:blood glucose ratio ≤ 0.6; clinical features consistent with GLUT1 Deficiency (epilepsy, movement disorders, ataxia, intellectual disability, dysarthria)
3. Presence of ataxia

Exclusion Criteria:

Individuals who meet any of the following exclusion criteria will not be eligible to participate in the study:

1. Inability to swallow liquids
2. Change in neurological medications (either medication itself or medication dosages) in the past 90 days
3. Use of fucose- or mannose-containing supplements within one year of enrollment
4. Presence of hepatic, renal, or concomitant metabolic disorders
5. Subjects who are pregnant, breastfeeding, or planning to become pregnant within one year of enrollment
6. Enrollment in an investigational new drug trial for GLUT1 Deficiency within one year of enrollment

The trial aims to recruit 12 to 16 participants.

Study Timeline

The study will last approximately a year (could be more or less depending on the rate of enrolment, meaning how fast people can make it to the study). After the study is finished, there may be several months needed for full analysis and compilation of data before results are released. 

Before beginning the trial, participants will undergo blood tests and assessments of liver function, kidney function, and electrolytes. Participants will then be randomly assigned to receive either fucose or placebo for 12 weeks, after which they will switch treatments for another 12 weeks.

At the end of the study, participants who experience benefits from fucose treatment can discuss continuing it; however, at that point, fucose would need to be purchased by the participant.

Additional Study Information

• The trial will be conducted at Oregon Health & Science University (OHSU).
  
• Participants must remain stable on all medications, including the ketogenic diet, for at least three months before enrollment.
  
• Fucose is a white, sweet-tasting powder that will be delivered in liquid form, either orally or via feeding tube, three times a day. The placebo will be very similar in color, shape, and taste to fucose, designed not to cause any metabolic effects in the body, and not having any sugars that could “break” ketosis. 
  
• The dose will be determined by body weight.
  
• The study does not yet have a start date. Dr. Starosta is awaiting FDA approval of the Investigational New Drug (IND) application, which has been delayed due to the government shutdown.
  
• Once FDA approval is received, the OHSU Institutional Review Board (IRB) will review the study. The IRB has already reviewed previous versions of the study, and it is expected that the IRB review once the FDA allows the study to proceed will be relatively quick. The trial will begin once IRB approval is granted.
  

I would like to thank Dr. Starosta for meeting with our community, sharing this valuable information, and all the work he has put into making the trial a reality. We also thank all of the supporters of the G1DF who have helped make this possible.

To learn more about Dr. Starosta and fucose, please visit the previous blog post linked here.

Thank you for visiting the blog!

If you have any questions, please contact me at [email protected].