Tuesday, January 15, 2013 @7:48 PM
Are there any cures?
1. Liver transplant (based on the research article)
Domino liver transplant: a transplantation in which a multiorgan from donor A is being transplanted in patient B and B transplants an organ to patient C.
Patients who received liver transplants were found to have increased levels of branched-chain alpha-keto acid dehydrogenase to at least similar to those patients with mild MSUD. However, if the patient was already intellectually impaired, this liver transplant has no effect on it. Patients no longer require protein restricted diets and no longer had metabolic decompensation.
In the research article, scientists were testing for the effect of domino liver transplantation. Patient 1 had MSUD and patient 2 had hepatitis-C-induced cirrhosis and a hepatocellular carcinoma in the right lobe of the liver.
Donor for patient 1 was an unrelated woman who suffered brain death. So patient 1 received the liver from her and his liver is transplanted to patient 2 using the "piggy-back" method, where as much of the hepatic veins, portal vein and hepatic artery was conserved as much as possible, to be joined to recipient's veins.
After transplantation for both, concentration of amino acids were tested for both patients. For patient 1, his plasma concentration of BCAA decreased to near normal levels. There was no hint of metabolic , but is still at normal levels. He did not develop MSUD.
Conclusion: both patients are cured :D
Research article:
http://onlinelibrary.wiley.com/doi/10.1002/lt.20744/pdf
2. Gene therapy
It is still being tested in labs and is not done on humans yet.
They cultured cells from an MSUD patient. They are skin fibroblasts with a mutation in the E2 subunit of BCKDH. They expressed less than 2% of BCKDH activity as compared to normal cells. They used a retroviral vector to deliver normal E2 genes into the mutant cells. After the gene delivery, the level of BCKDH increased to 93% of normal cells.
After that, they decided to develop a MSUD mouse model to use for researching gene therapy. They mutated the E2 subunit of BCKDH by inactivating it. The mouse pups were normal at birth, but within hours they became sick and died. This is because there is a total loss of enzyme activity because the E2 gene is completely inactivated.
they solved this problem by creating a new transgenic line of mice, where the E2 gene is under control of tetracycline, so gene expression can be controlled by adding/removing tetracycline from drinking water. Since gene expression can be controlled to how MSUD is like in humnas (low enzyme activity, not total loss of activity), the mice do not die. So they can be kept alive for several months to test gene therapy on them.
They would still have to do a lot more tests on animals before gene therapy can be done on humans. But there is a possibility of gene therapy for humans with MSUD to happen someday.
Reference:
http://www.msud-support.org/index.php?option=com_content&view=article&id=258%3Agene-therapy-for-msud-takes-a-big-step&Itemid=120