To this point there is no cure for MCT8-AHDS however there are a few (experimental) medical alternatives.
Medical Alternatives:
Propylthiouracil (PTU)/Levothyroxine
This combination of medication is probable the most accessible.
The treatment combination helps reduces the high blood T3 which is the cause of inability to gain weight, malnutrition and reduces toxicity to organs.
The treatment is aimed to increase the serum T4 concentration and decrease that of T3. Higher T4 will partially relieve the thyroid hormone deprivation in the brain, given the combination of the natural brain barrier for T3 and the absence of MCT8 mediated T3 transport. A decrease in serum T3, through the administration of PTU, an inhibitor of type 1 deiodinase (D1) will reduce the conversion of T4 to T3 in peripheral tissue and decrease the hypermetabolism. Incidentally, T3 is generated from T4 in brain by type 2 deiodinase, not inhibited by PTU.
PTU has several effects, one is to block the synthesis of T4 and the other is to block the conversion of T4 to T3 by D1; that is in the many body tissues but not in brain. Giving PTU will reduce the formation of T3 in the body and thus decrease the burning of calories. Giving T4, will overcome the effect of PTU on the synthesis of T4 and as D2 is not affected, will not further reduce the already compromised supply of T3 to the brain.
Experimental Medical Alternatives:
The subsequent treatments have been shown to both rescue neuro-motor deficiencies in animal models and reduce blood toxicity. In humans, these experimental treatments have so far shown a metabolic stabilization which is important for general well-being. Neuro-motor rescue in humans is currently being researched for both drugs.
Triac (Tiratricol)
This medication is commercially available in France for a different condition. The commercial name is Teatrois and it’s produced by Rare Thyroid Therapeutics, Sweden. At this point the use of Triac for the treatment of MCT8 deficiency ( Allan-Herndon-Dudley syndrome) is off label.
Triac is a thyroid hormone analogue. Triiodothyroacetic acid is also a physiologic thyroid hormone that is present in the normal organism in low concentrations. Triac treatment could result in normalization of the abnormal serum TH values in AHDS patients. Furthermore, Triac could replace the function of T3 in tissues that depend on MCT8 for TH uptake (e.g. brain).
How is this medicine expected to work?
This medicine has a similar structure to and works in the same way as the thyroid hormone T3. The difference is that, unlike T3, it can enter developing nerve cells without the MCT8 transporter protein. This is expected to allow the medicine to enter nerve cells in patients with Allan-Herndon-Dudley syndrome, replacing the hormone that they cannot transport, and thereby allowing the nerves to develop properly and relieving symptoms of the disease.
On 12 October 2017, orphan designation was granted by the European Commission to Medical Need Europe AB, Sweden, for tiratricol for the treatment of Allan-Herndon-Dudley syndrome.
DITPA
The FDA has approved a protocol to treat pregnant women carrying a fetus with a MCT8 gene mutation causing AHDS.
The protocol applies to pregnancies no more than 8 weeks along. The gender of the child will be determined from the mother’s blood. If the child is male, a further investigation aiming to determine if he is affected will be carried out.
If the baby carries an MCT8 Deficiency related mutation then treatment will start immediately. A thyroid hormone-like compound (DITPA) will be taken by mouth. This compound, unlike thyroid hormone can reach the brain of the child as it bypasses the mutant MCT8 transporter. By reaching the brain early during development it is the hope that DITPA can prevent some if not all of the neurological deficits seen in children with MCT8 mutations.
DITPA is not available for purchase. For further information, please contact Dr. Refetoff (University of Chicago) or Dr. Weiss (University of Miami) rweiss@med.miami.edu Tel 1-305 243-1944.
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