National Gaucher Foundation Conference USA September 2000

Gaucher's News Contents

About 180 individuals with Gaucher's disease and their families attended a two day Conference in Arlington, Virginia on 12-13 November 2000 to hear experts from the USA and Israel talk about the latest information on Gaucher's disease.

Robin Berman, medical director and founder of the National Gaucher Foundation in the USA, opened the Conference by saying that the Gaucher's community where-ever they live is one large, special family.

She spoke of her own family where three of her six children have Gaucher's disease. Her second child, Brian was the first patient to be treated with enzyme replacement therapy in 1983 by Dr John Barranger and Dr Roscoe Brady.

Brian was 21 in December 2000 and married the same month. He is very well.

Another young man, Jessie, was introduced to the audience. He was diagnosed at 5 years of age and is now 19 years old and 6' 4".

'When he started Ceredase at the age of 13 years, he grew 9 inches in a year,' his mother told the meeting.

'Enzyme replacement therapy has enabled him to lead a normal, healthy teenage life graduating in History and Maths. He plans to become a teacher.'

Gene Therapy

Dr John Barranger, Dept of Human Genetics, University of Pittsburgh, spoke about three ways to help Gaucher's disease:

He said that the principle of enzyme replacement therapy could be used for 50 lysosomal diseases and Gaucher's disease is their model. However there is still room for enzyme therapy to be even more effective.

The idea of substrate deprivation is good and important for neuronopathic Gaucher's disease as it can get into the brain.

Dr Barranger spoke about his first trial of gene therapy on four of his patients with Gaucher's disease. He said that the trial only corrected enzyme deficiency in one out of four patients and in that case the enzyme was reproduced for three years.

He discovered that this form of gene therapy could be carried out with no risk to the patient. But he and his team need to improve its efficiency and he was looking at ways to do this. He felt that gene therapy could be achieved in the next five years. He was also looking at other target cells in which to introduce gene therapy whilst continuing working with haemopoetic cells of patients (the method used in his first trial).

In animal experiments, he is testing viral vectors placed in muscle stem cells as well as gene transfer into liver and brain cells. He is also carrying out laboratory tests on anti-natal gene therapy and substrate inhibition in a 'Gaucher's mouse'.

Overcoming the obstacles to Gene Therapy

Dr Pamela Becker, Division of Gene Therapy, University of Massachusetts Medical Center, said that out of 10 patients on three trials of gene therapy for Gaucher's disease, there was no evidence that the gene transferred had remained.

The problem was the need to isolate premature stem cells, get the gene into these cells and transfer them back into the body so they can be taken up and continue to work normally.

She was currently working on solving several problems involved in making gene therapy work.

Genetic Mutations

Dr Ellen Sidransky, a clinical geneticist at the National Institutes of Health in Bethesda , Maryland, said that over 200 mutations for Gaucher's disease had been discovered. However a gap remained between linking a genetic mutation to the outcome of the disease. Even siblings and twins have been described as have varying degrees of symptoms. She also pointed out that residual enzyme activity or lipid storage does not denote severity of symptoms.

She said that five mutations account for 93% of mutated genes in her Type 1 Ashkenazi Jewish patients. They are N370S, 84GG, IVS2+1, L444P and R463C. But these five only account for 49% of the mutant gene in her non-Jewish Type 1 patients and they are not necessarily the most common mutation in Type 2 or 3 Gaucher's disease.

She also said that merely screening by PCR (a method of screening) for the presence or absence of specific mutations is often inadequate because there are quite a few patients that more complex mutated genes.

Infusion Related Issues

Dr Gregory Pastores said that there still remained many unanswered questions in relation to Gaucher's disease.

Not everyone who has inherited a genetic mutation for Gaucher disease from both parents has symptoms. Who is at risk? Why do some people develop major complications and others not? Why are siblings, even twins, different in how their disease progresses?

He stressed however the major goal for people with Gaucher's disease is to have improved quality of life. People with the disease should be able to work and have fun.

He believed that any sign (eg slightly low blood counts, slightly enlarged spleen) for someone who also has an enzyme deficiency for Gaucher's disease, indicates that that person should be evaluated on a regular basis to see if treatment is necessary. Likewise if a child had no symptoms but shows progressive disease signs (eg through blood tests, X-rays or scans), that child should probably receive treatment to prevent onset of a complication

He also said an exercise programme is necessary.

Primary tests include blood tests, MRI (of liver/spleen, spine/femurs) and X-rays. Secondary tests are Echocardiograms for pulmonary hypertension, Bone Mineral Density, Ultrasound or CT scans and bone marrow scans but not all these are necessary for everyone. The type and frequency of testing should be individualised for each patient.

Patients need to consult specialist experts eg cardiologists, haema-tologists and rehabilitation experts as the need arises.

They also need support groups including patient associations and social services. The internet and newsletters have become an effective means of communicating information to patients, their families, their physicians and other carers.

Fosamax Trial

Dr Gregory Grabowski described the Fosamax trial he is carrying out (reported in Gaucher's News, February 2000 and January 1999) where use of this bisphosphonate drug can be tested to see if there is an improvement in the bones of patients with Gaucher's disease. The study is to look at fractures and general bone mineral density.

Interim results are due shortly although the full complement of 84 patients is yet to be assigned. The trial is taking place in the USA and in Israel.

Bone Disease

Dr Henry Mankin gave a similar talk to that given at the Royal Free Hospital (reported in Gaucher's News, February 2000).

Gaucher's News Contents

Source: Gauchers News March 2001.
© Copyright Gauchers Association 2001