James Stewardson Treatment Programme

Last Updated 20th November 1999

November 1999 - Bipap Fails to save James

July 1999 - Further Red Cell Transfusions

April 1999 - Daily Shark Liver Oil Dose (contains Batyl-Alcohol

July 1998 - Daily Cod Liver Oil Dose

January 1998 - Red Cell Transfusions

July 1996 - Plasma Therapy Treatment

History - James's Medical History

Bipap Ventilator Fails to Save James

James responded well to the exchange transfusions he was receiving every 3 or 4 weeks since July and the combination of this treatment and the oxygen whilst sleeping enabled James to get stronger. However, since the middle of September James deteriorated and this led to breathing problems during the day.

It seemd the only chance for James was to get him on a bipap (partial mask ventilator) to help with his breathing. Tragically for James the bipap didn't work and James died of respiratory problems on November 12th 1999.

Further Red Cell Transfusions

With James's deteriorating slowly over the last few months we suggested to our haematologist Dr. Andrew Will that James should start a programme of red cell transfusions again. This will prove whether any sustainable benefit can be realised from the transfusions and thereby give added reason to give James a Bone marrow transplant in the near future.

At the moment James is not well enough to undergo a BMT and the associated chemotherapy treatment. Dr. Will has stipulated there must be significant improvement in James before he would go ahead. 2 year old Sister Georgia is a perfect bone marrow match for James.

James will undergo the transfusions about every 3 weeks for the next few months if necessary.

Shark Liver Oil Treatment

James has started taking Batyl-Alcohol contained in a product called Alko-Mar which is made from Shark Liver Oil.

Alko-Mar comes in small capsules and James has 6 per day, they each contain 500mgs of shark liver oil and 250mgs of alkoxyglycerols.

From various investigations by James's Manchester Haematologist, Dr. Andrew Will, the Alko-Mar seems to be the best product which contains batyl-alcohol.

This treatment has been suggested by Professor Susan Hollan who found that the Hungarian TPI brother with the neuromuscular problems associated with TPI deficiency also has a plasmalogen deficiency, batyl-alcohol is meant to improve this deficiency.

From blood samples of James, Professor Hollan confirmed in late June 1999 that James also has a plasmalogen deficiency.

Further details of Batyl-Alcohol Treatment

Cod Liver Oil Treatment

James started to take Cod Liver Oil on the advice of Professor Susan Hollan on February 3rd 1998, at the same time James was also having red cell transfusions about every 5 weeks. Soon after taking the Cod Liver Oil we noticed an improvement with his hand control and foot movement, his hands were becoming claw like and his ankles turning in and getting stiffer. His hands became very supple again and his ankles loosened up.

In early April we took James off the oil, to allow a period of time without James taking the oil for purposes of the blood samples Professor Hollan was to receive. It was very important the blood samples from James were free of the effects of the oil. Professor Hollan eventually got James's blood samples in the first week of July, these had been taken from James at Kings College Hospital during his transfusion on May 19th. We started James back on the oil on May 21st after returning from London and we very soon saw the benefits return with regards James's hands etc,etc.

Red Cell Transfusions

James started on a series of red cell transfusions in October 1997. The aim of this treatment programme is to replace James's red cells with donor cells over a period of about 5 months. This will be initially via drip transfusions of about 250 mls and if necessary exchange transfusions.

On January 9th 1998 James received his 4th transfusion, an exchange of about 360mls. Previously James was given 250mls in October 97, 200mls in November 97 and about 450mls in December 97.

Results from the biochemical analysis of James's blood taken before, immediately after and 24 hours after his exchange transfusion on December 12th look very encouraging. In the pre and post transfusion analysis the levels of TPI enzyme found in the white cells were higher and levels of the substrate DHAP were lower. These results indicate that the reversal of the block in metabolism could be detected in Jamesís cells and complementation of TPI from red to white cells is actually happening. This further indicates a BMT might be a possible treatment for TPI deficiency. These tests will be repeated after James undergoes his next transfusion in February.

Plasma Therapy Treatment

James Stewardson underwent treatment for TPI Deficiency at Kings College hospital in London in July 1996. The treatment involved 5 consecutive daily sessions of donor plasma replacement therapy. Below is the report issued by Kings in November 1996 detailing James Stewardson's Treatment.

TPI Research - Plasma Therapy - November 1996

"One approach to the treatment of some inherited diseases caused by lack of an essential protein within the bodyís cells is to replace the missing protein. Research at Kings College Hospital, London, has shown that this may be possible in TPI deficiency. By growing the cells of children with TPI deficiency in plasma they were able to show the metabolic defect could be overcome in the cultured cells. As plasma contains small quantities of TPI this raised the possibility that TPI in plasma could enter the patients cells possibly providing benefit. Based on these results, doctors at Kings attempted a trial of plasma therapy in James Stewardson, a three year old boy with severe TPI deficiency. It was not known whether there was sufficient TPI in plasma to replace the enzyme missing in Jamesís cells and detailed biochemical testing was needed to answer this question. James completed the five day treatment successfully, though on the last day developed an allergy to plasma preventing further therapy. No reversal of the block in metabolism could be detected in Jamesís cells. Neither was there any clinical evidence of benefit in this short trial. However, in view of the laboratory results in cultured cells the possibility of increasing the TPI content of transfused plasma is being examined for future clinical evaluation. This is the first new treatment to be tried in TPI deficiency since the disease was first discovered thirty years ago. The doctors at Kings are cautious not to raise false hopes in a disease for which no effective treatment currently exists but if successful, believe the outcome of their research may open up new approaches to replacing the enzyme missing in TPI deficiency, utilising either bone marrow transplantation or gene therapy."

Alastair J Bellingham - Professor of Haematology

The treatment was preceded by the following Kings TPI research project report :

"TPI deficiency is characterised by reduced enzyme activity in all tissues, accompanied by metabolic block. The mechanism by which these biochemical changes cause multisystem disease, including severe neuromuscular problems, is poorly understood. At present only supportive treatment is available. Enzyme replacement therapy has been used with limited success in other inherited disorders such as Gaucher's disease. To evaluate the possibility of replacing TPI enzyme in TPI-deficient patients we have attempted to complement deficient cells in culture. So far, our experiments indicate that it may be possible to achieve intracellular enzyme replacement and reversal of the metabolic block in the test tube. In the human body, however, the situation is less straightforward. TPI has a short half-life in the circulation and question marks remain about the delivery and uptake of cellular enzyme in the areas worst affected particularly the nervous system. The possibility of enzyme replacement in the clinical situation is currently being investigated."