Today is February 28th, it is Rare Disease Awareness day. Rare disease (or orphan disease) are diseases that have a small incidence among the population. We talking about patients fewer than 200’000 (Source: raredisease.org). That’s paradoxically a lot of patients suffering from diseases most of the time misunderstood or as I like to call a scientific “black box” although 80% of them are genetic and 50% affect children.
They are challenging for two reasons: parents and patients have to visit many doctors to find a cause of their disease condition and once identified they often end up with the same answer: no known cures. No cures because the number of individuals affected are small and making a drug costs a lot of money.
Don’t blame Big Pharma, Big Pharma is a business and like another business he has to make benefits out of its products to live. Unlike other markets in which return on investment are fairly good (e.g. hi-tech companies), pharmaceutical companies gamble high on R&D with a high risk on dead-end with a big negative value (important money loss). To give you an idea, only 1 out of 10’000 compounds that have shown promising hit in a screening platform will end up FDA-approved, in other means starting to bring cash in.
I am a scientist and you may know from my blogs that my research focus on the blood-brain barrier. Its play an important role as a gatekeeper, a cellular custom border patrol allowing the entrance of documented aliens necessary for the proper brain functions and to block the entrance of undocumented or suspicious aliens that may have harmful activities inside the brain.
We know that the blood-brain barrier breaches during several neurological diseases, but yet we poorly know how genetic disorders may affect the blood-brain barrier integrity. There are indeed some rare diseases that have a dysfunctional BBB but because it affects neurons, it mostly go unnoticed and are classified as neurological disorders. To raise awareness about rare diseases, I wanted to present two of them that have been linked to some of my research:
– Allan-Herndon-Dudley Syndrome (AHDS):
AHDS is what I call a fairly rare disease (<100 cases) but we may just have tipped an iceberg. It is what we call an X-linked mental retardation. It mostly affect boys and rarely girls. Why? If you remember your high-school biology class, mens have a XY pair and women have a XX pair. The X always come from the Mom, the Dad in the other hand gives either a X (thus XX) or a Y (thus XY). The mom carries the mutation, thus the son display the disease.
The disease is very dramatic has its sign appears during the first year of life. Infants start to show problems in their psychomotor growth and cognitive development. According to Dr. Vatine, these kids brain somehow stop growing around 8-12 months, whereas their body keep developing normally. They barely babble words, have severe impairment (require constant care) and have no cures.
These patients suffer from a mutation in MCT8 (monocarboxylate transporter 8), a nutrient transporter involved in the uptake of bioactive thyroid hormone (T3). Patients show a high plasma level of T3, yet some studies suggest a low T3 level in the cerebrospinal fluid. Although mouse models of the disease (MCT8-knockout mice) have been developed, they failed to fully represent the signs of the disease. A problem observed with rodents is the interspecies differences, rodents are not humans and sometimes they do not reflect human diseases. It has been that indeed OATP1C1 (a nutrient transporter expressed only in rodent BBB) can transport T4 (the precursor of T3) into the BBB. Humans do not have any identified T4 transporter.
If you want to know more about the AHDS syndrome, feel free to consult the SMILE/Sherman foundation: http://mct8.info
– GLUT1 deficiency syndrome (GLUT1-DS)
The brain surely not run on Dunkin Donuts, but run on something highly enriched in their donuts: sugar. Glucose in particular. The brain is a high glucose consumer. Compared to its size (1% of the total body mass), the brain take over 20% of glucose of your total intake. However, if you fast or starve on an Atkins diet, the brain can bypass the glucose as source of energy and can use fatty acids degradation byproducts, in particular ketone bodies as a alternative source of energy. Yet there is this disease called GLUT1-DS or De Vivo Syndrome.
In this disease, the patients have in the mutation in GLUT1 transporter, a nutrient transporter that uptake glucose from the blood to the brain. These kids are doing fine during their first year and then start to develop epilepsy type of seizures in the same age, that is very unusual for children (usually toddlers and kids have absence seizures or “petit mal”). These kids fail to respond to their anti-epileptic drugs and their only positive outcome is the diagnosis and the change in supplementation into a ketogenic (Atkins) diet.
I am wondering if such condition may be more spread than expected, as nearly 30% of patients have refractory response to common anti-epileptic drugs
Hopefully, there is some good news ahead from these patients, as some clinical trials with trihepatonin have shown some positive outcome as a dietary supplement in lieu of the ketogenic (Atkins) diet.
If you want to know more about the GLUT1 deficiency syndrome, feel free to consult the GLUT1 foundation: http://www.g1dfoundation.org