The Virtual World Conference on

Rare Diseases

In the summer of 1983 my son Brian Berman at aged 3 was diagnosed with Gaucher.

We were told there is no treatment, and that he will die soon.

We were completely devastated, but my mother, had gone to Israel a couple months prior, and had met the Director of the Weitzmann Institute. She called him and he told her that the world expert on Gaucher Disease, Dr. Roscoe Brady, had his lab at the NIH, 10 minutes from our home.

I  called Dr. Brady and asked him, “do you have anything to help my child?”

He said, “if you knew what I had, you would come running to my door”- which is what I did- I gave up my medical practice, and worked gratis for Dr. Brady in his lab. At that time, Dr. Brady, who, in 1964 had discovered the enzyme deficiency that caused the Gaucher Disease syndrome, and had attempted to give native placental derived Glucocerebrosidase to little clinical effect, was developing the mannose terminated version.

My son was very ill, on the edge of high output cardiac failure from a massive spleen, severe anemia and thrombocytopenia.

Dec. 22, 1983, without prior animal studies, he was infused the very first targeted enzyme for a lysosomal disorder.

Over the next 7 weeks, we all witnessed a miracle. His spleen reduced in size, his blood counts, energy, and mobility dramatically improved. Two subsequent on- off cycles demonstrated clear therapeutic efficacy.  Subsequent patient trials led to the FDA approval process in 1991. Dr. Brady’s lab was partnered with the fledging company headed by Henri Termeer. This company became Genzyme Corporation which commercialized the enzyme then called Ceredase. Subsequently, the enzyme was generated utilizing genetic technology followed by two other companies each utilizing unique technology to generate enzyme.

In  coordination with Dr. Ari Zimran we obtained  approval by the Israel Ministry of Health and subsequently global approvals ensued.

Although this series of events could not occur in today’s world, it should empower everyone to realize that our gold standard of the double blind, randomized, placebo controlled trials are not the most powerful way of making big changes in the world of medicine.

Many physicians and scientists go into their respective fields because of personal experience ie the N of one. It is in my view, arrogant and foolish to discount, even scoff at what still too many disdainfully refer as anecdotal or observational data.

Henri Termeer himself said many times, to many audiences, that it was seeing the incredible changes in one little boy that inspired him, against many odds, and many naysayers, to build the company that really put lysosomal storage diseases on the map.

PS- I have 6 children, – by spring I will have 21 grandkids, 15 of whom come from my 3 sons with Gaucher-

Biomarkers are surrogate markers of disease, in the case of inherited lysosomal storage diseases (LSDs) usually being proteins or metabolites secreted by storage cells into the blood or urine. Biomarkers can be employed to assist diagnosis, to monitor disease and to assess correction of storage cells by therapeutic intervention. The discovery and application of biomarkers will be exemplified for Gaucher disease (GD). In this LSD, due to inherited deficiency of glucocerebrosidase, lipid-laden macrophages (Gaucher cells) accumulate in various tissues. Several proteins have been identified that are specifically produced by Gaucher cells and secreted, causing elevated levels in plasma. Examples are chitotriosidase, a chitinase, CCL18, a chemokine, and a soluble fragment of GpNMB. More recently, it has been recognized that Gaucher cells produce and release glucosylsphingosine (GlcSph; aka lysoGL1), deacylated glucosylceramide that is produced by acid ceramidase in lysosomes.  GlcSph levels are markedly increased in plasma and urine of GD patients. The value of plasma biomarkers for the clinic will be discussed. In addition, attention is paid to lipid-laden macrophage derived proteins and deacylated sphingolipids (aka lyso-lipids) as future biomarkers for other sphingolipidoses.