University of California, San Fransisco
20th March 2006

The Lowe Syndrome Trust (a small voluntary charity), is delighted to announce an award of £50,000 to Professor Robert L Nussbaum, MD Institute for Human Genetics and Department of Medicine, University of California San Francisco.

 

Lowe Syndrome charity chair Lorraine Thomas stated "Building on the current research projects funded by the Lowe Syndrome Trust, this project presents the next small but significant step in a very long journey-hopefully leading to an understanding of the basic underlying defect.

 

If it results in a deeper understanding of how the diseases comes about, it may make the medical profession much better in developing therapies". Professor Nussbaum has been been an outstanding leader in efforts to understand the rare X-linked disease known as the oculocerebrorenal syndrome of Lowe (OCRL), characterized by congenital cataracts, Fanconi syndrome of the renal proximal tubules, neurological dysfunction, and developmental delay.

 

Professor Nussbaum discovered the gene responsible for OCRL by positional cloning and demonstrated that the gene encodes a phosphatidylinositol (4,5) bisphosphate 5-phosphatase that was shown to be enriched in the trans-Golgi network and early endosomal compartments. Current treatment is purely symptomatic and palliative. The relationship between the enzyme deficiency and the pathophysiological abnormalities in OCRL remain obscure.  In  previous experiments, Mice lacking the OCRL gene had no signs of the disease.

 

Professor Nussbaum will investigate why these mice are protected from a deficiency in this enzyme and how this information might be exploited to expand our understanding of this enigmatic disorder and develop new, specific therapies.  On 20th March 2006 a meeting organised by the Charity was held at the UK  Institute of  Child Health attached to Great Ormond Street Children's hospital. Professor Nussbaum presented and discussed the project with the Lowe Syndrome Trust scientific advisors and researchers who hope to be able to Dr Naussbaum's results in their research projects. The meeting also discussed the possibility of joint collaborative research projects and the establishment of a clinical and cell tissue database.      

 

Studies indicate that the clinical, physiological manifestations of an OCRL-1 mutation do not singularly account for just the clinical manifestations used to describe Lowe Syndrome; rather they can be presented as another phenotype describing a different disease (Dent’s Disease) which has similar renal problems but very distinct clinical characteristics.This grant award will secure Dr Nussbaum's funding for the first year of a 2-year research project. To enable the funding of the second year the Lowe Syndrome Trust will be holding further appeals and fundraising events.  

 

  The main genetic research and coordination for Lowe Syndrome has been conducted in USA by a team lead by Robert Nussbaum, formerly Senior Investigator and chief of The National Human Genome Research Institute (NHGRI) in Washington USA. The NHGRI team are: Robert Nussbaum, Sharon F. Suchy and Ti Lin who have created A Lowe Syndrome mutation database and a Lowe Mouse. In November 2002 Robert and Sharon published a paper on Lowe Syndrome and Actin Polymerization.   

 

The LST scientific and medical advisory board is:
Dr Anthony Norden, Addenbrookes Hospital, Cambridge
Dr William van’t Hoff, Consultant Nephrologist, GOSH.
Professor Robert Unwin, Professor of Nephrology & Physiology, UCL.
Professor Shamshad Cockcroft, Department of Physiology, UCL.
Professor Philip Beales, Hon Consultant in Clinical Genetics, ICH.
Professor Peter Cullen, School of Medical Sciences, University of Bristol 
Dr David Taylor, Opthalmic Surgeon, GOSH

Mike Harrison Consultant in Pediatric Dentistry, Guys Hospital London 

 

The trustees are: Ms Lorraine Thomas (Chair), Ms Carolyn Mitchell, Mr Jonathan Ross, Ms Catherine McNaught, and Ms Penny BiziouPatrons include: Baroness Susan Greenfield CBE, Sir Richard Sykes DSc FRS, Tom Conti (BBC Radio 4 appeal April 15th), Tris Payne, Tony Hadley, Jono Coleman, Richard Park, Richard Desmond, David Prever, Susie Webb and Penny Lancaster. 

 

For more information contact:
c/o Lowe Syndrome Trust 77 West Heath Road
London NW3 7TH
ENGLAND
Phone: (+44) 208-458-6791
E-mail: lowetrust@homechoice.co.uk