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I would also like to start this section thanking all the researchers, doctors and health care professionals that work together in order to discover and apply new treatments and therapies which benefit the most vulnerable patients.

Among them, we can luckily mention several outstanding professionals: Doctor DerksDoctor WeinsteinProfesor Youngmok LeeDoctor GrünertDoctor WortmannProfesor Veiga-da-CunhaProfesor Schaftingen…etc.

GENE THERAPY

Doctor Weinstein has spent many years researching on GSD gene therapy together with Professor Youngmok Lee. They have achieved many things and received many prizes. Unfortunately, being a rare disease with a low number of patients, most research companies are not interested since they may not have too much profit out of it. This is why a lot of support and funds are urgently needed for research, especially for GSD type 1b, which is even rarer than the others.

One of the main research projects is the “gene therapy”. In my case, it is in vivo somatic gene therapy to treat the glucose problem and ex vivo to treat neutropenia.

No worries! I will also explain this with baby words 🙂

As I mentioned before, I have a mutation in one of my genes so my liver is not getting the right information to work properly and it is not breaking glycogen down into glucose. The idea is to put inside my body (in vivo) the right version of my mutated gene.

This gene is introduced in a virus which viral component has previously been removed. The virus is inserted into my liver to leave the right gene inside. This gene modifies certain liver cells so that they start working properly. This is how my body will be able to produce glucose and avoid hypoglycemia.

This is not called a cure but a therapy. It will not cure me for good but it will make my body work properly for years. After some time I will need some reminders (as if it was a vaccine) to reintroduce the right gene into my body again.

This therapy has been tested in mice and dogs for several years. Watch the following video in which Dr. W explains the gene therapy and you will see how these animals suffering GSD and having severe hypoglycemia are treated with the right genes. Not only they quickly get better but they also manage to maintain this improvement for long time. The levels of glucose in blood remain stable and the storage of glycogen decreases. Overall, all indicators improve.

All this would help me a lot and would also be useful as a model to cure other liver diseases. Currently, these tests are being carried out for GSD 1a. We hope all will go well and that the gene therapy can also be developed for GSD 1b. This will require further research so more funds are needed.

In my case, even if the liver problem was solved, I would still need to deal with the neutropenia. For this challenge we cannot use the same approach because the problem is not in the liver but in the bone marrow. The virus used to introduce the right gene in the liver cannot be used for the bone marrow. This is why the method consists on extracting the bone marrow’s stem cells and once outside the body they go through gene therapy. Some of these stem cells are modified and start working properly. They are reproduced to get millions of them and they are reinserted in the bone marrow which becomes more functional and results on a stronger immune system.

TREATING NEUTROPENIA AND NEUTROPHIL DYSFUNCTION WITH AN SGLT2 INHIBITOR

Another very important line of research and treatment is the repurposing of a drug called “empagliflozin” for GSD 1b patients.

The treatment is based on a research publication (Veiga-da-Cunha et al –PMID: 30626647). In GSD 1b patients, with G6PC3 or G6PT deficiency, the accumulation of 1,5AG6P inhibits glycolysis, something which affect negatively neutrophils since their energy metabolism depends upon it. Therefore, the research suggests that increasing the renal excretion of 1.5AG could be an alternative or complementary treatment of neutropenia in GSD 1b patients. This renal excretion is facilitated by an existing drug called empagliflozin which is normally used for diabetes type II and the use for GSD 1b is a very good example of drug repurposing.

Other articles have been published since then by Doctor Derks and other wonderful Doctors which abstracts you can find through these links: Wartmann et al and Grünert et al

Even a GSD family had the wonderful idea and creativity to make this explanatory video.

As most of you know, I was one of the first persons in the world to follow this off-label treatment at the UMCG in Groningen in September 2019.

Since then, we have written an article in the Journal of Inherited Metabolic Disease, we have published podcast in the University Medical College of Groningen’s area of research, we have participated as panelists in several webinars, conferences, University lectures, together with our dearest Doctor Derks, not only about the off-label treatment with empa but also about the set-up of an internet platform www.emergencyprotocol.net  which generates tailored emergency letters for some metabolic diseases’ patients, including GSD.

Other ongoing research projects:

  • More effective treatments for Inflammatory Bowel Diseases
  • Find products more effective than cornstarch and with better flavors