Few days ago, I experienced as a scientist one of the greatest gratitude moment you can experience: being awarded a research grant for funding my research.
This was not an ordinary grant for me, as it came directly from the GLUT1 Deficiency (G1D) Foundation. This is a grant getting funded by money fundraised by patients suffering from G1D and their families, the sum of tireless effort and time of baking sales, fundraising walks and other activities to raise funds to promote basic and clinical research in order to find a cure of G1D patients.
- What is GLUT1 and what it is function in the brain?
Glucose is the main source of energy in the brain. We estimate that almost 25% of daily glucose is exclusively reserved for the brain tissue. Given that the brain average weight is only 2% of the total body weight, we can easily understand how the brain is overwhelmingly dependent on glucose.
Glucose is a small molecule, but yet glucose is a highly polar molecule. It dissolves very well in water but it dissolves very badly in fat. Because cell membranes are made of fat (phospholipid bilayers), glucose cannot freely diffuse across the BBB and needs a carrier that will shuttle glucose from the blood to the brain.
GLUT1 is a member of the glucose transporter superfamily. We estimate over 14 different GLUTs expressed in mammalian cells lithesome specificity in where such transporters are expressed. At the BBB, GLUT1 is considered as the predominant isoform expressed, although some studies suggested the presence of GLUT3 and GLUT4 at mRNA levels but no one demonstrated their presence at protein levels and their presence as functional transporters. GLUTs function as facilitated carriers, they do not need energy to function and only rely on gradients (more concentrated to less concentrated to function).
2. GLUT1 deficiency syndrome (G1D)
Glucose transporter 1 deficiency syndrome (G1D or GLUT1DS) is a genetic disease firstly coined by Pr. Daryl De Vivo (University of Columbia Medical College) in 1991 in the seminal paper published in the New England Journal of Medicine.
G1D may have been already a existing disease but by its nature may have been largely undergo misdiagnosed as an type of epilepsy.
The major clinical feature of the disease is the onset of epileptic seizures during early infancy, usually by the age lesser than 1 year old. The diagnosis is usually reinforced by a spinal tap that usually note a low glucose level in the cerebrospinal fluid compared to normal range. The final diagnosis is usually obtain by measuring glucose uptake in patients red blood cells, however this procedure remains cumbersome and not systematically performed.
Patients respond in general poorly to their epileptic seizures and until now the major intervention with these children is the use of ketogenic diet (KD), a variation of the Atkin’s diet (no-carbs diet).
Under fasting condition, the body can break down fatty acids from the fat storage compartment into ketone bodies (acetoacetate, beta-hydroxybutyrate). These ketone bodies can used as alternative fuel for the brain and allow to function quasi normally.
The disease is triggered by mutations in GLUT1 transporter, yet the relationship between sites of mutations and severity of the clinical symptoms are not yet established.
The average number of G1D cases worldwide is relatively small (~250 patients) but it may be a more prevalent condition, as it is often misdiagnosed as an idiopathic type of epilepsy.
The KD is not the panacea and has its challenges and limitations, in particular in terms of dyslipidemia and also in following the dietary requirements and personalization.
Recently, the development of anaploretic diet using triheptanoin (short odd-chain fatty acid) supplementation may help improve the quality of life for G1D patients.
3. Why do we need fundraising and why researchers need grants?
Scientific research is a long and expensive intellectual endeavor with no guarantee of success to translate findings into patients.
In academic research, most of the money comes from public agencies such as the National Institute of Health (NIH). This money is originated by every citizens through taxes, thus we can say that research funds are made of “taxpayers money”
Because money is not an infinite ressource and you cannot ask taxpayers to pay ludicrous amount of taxes, funding agencies have to set funding priorities for diseases that have the highest priorities. Most of the time, this priority is determined by the prevalence of the condition. This is where we are facing challenges when you have a “rare disease”. Because “rare diseases” are by essence rare (less than 1 patient out of 100’000), funding agencies are reluctant to invest into this disease and pharmaceutical industries are reluctant to invest into a drug discovery program that will be costly and with little return to cover the cost.
This is why foundations are essential for us scientists. They provide us with funds that allow us to generate experimental data that are robust enough to be considered by special funding agencies (that support research on rare diseases) to take us seriously and provide us with a higher fund to further investigate such disease.
Funding agencies and foundations rarely if not never fund any projects without having it evaluated by a scientific broad that assess the validity of the science behind and the robustness of the investment to be made.
This is why I am very thankful to the G1D foundation to give me their trust in my research proposal and fund my work. If you want to help the G1D, you can donate them money through their donation page.
If you have another disease you want to contribute, please look up for a foundation held by patients or families, in particular support foundations that have a low fundraising maintenance cost (15% or less) and that have defined programs and goals including research grants and patient care.
Again, I would like to thank G1D and really looking forward to attend their 2017 meeting, with data as fruits of the scientific harvest made possible by this seed grant.