Project Shui for Tay-Sachs

Substrate Inhibitors   

                                                                                                                   Donate Now

*Video or Pictures of Tay-Sachs

Project Shui Home Page

Welcome From Shui
   What is the Cure Tay-Sachs Foundation?
   How Close are we to a Cure?
   *Rachaeli's Friends
   Sign up for Updates
*Bar Mitzvah Video Invite
What is Project Shui?

Thank You From Shui
   Internet Ads&Marketing

What is Shavuot?
Shavuot & Shui's Sister

What is Tay-Sachs?
Tay-Sachs Diagnosis:

      Part I

      Part II

   Genetics Made Fun
      *Lysosomes The Movie
      *Genetics 101 Video
Narrated by Alec Baldwin
   Genetics 101 Article

*Inspirational Videos

*Beautiful Faces of Lysosomal
*Tay-Sachs Talk
   *Connor Hopf Cure Tay-Sachs
   *2010 Faces of Tay-Sachs
*My Soul Sister-Molly Grace
*Our Star Dakota
   *Rachaeli's Song of Love
   *Elise-A Child Living with Tay-Sachs
   *Last Laugh
   *Meet Gavin

Tay-Sachs in the Media
Glee Sectionals
   *Grey's Anatomy Sweet Surrender
   *Law & Order SVU MERCY
21 Below Documentary
Legal & Financial Issues

   What is Wrongful Life?
   Right to Live in the United Kingdom
   How to Pay Medical Bills?
   Social Security Disability
   CHIPRA-Insurance for Kids
   Medicaid Waiver Programs
   Katie Beckett Medicaid
   Who is Katie Beckett?
Why Do We Need The
Katie Beckett Waiver?
Eligibility for Katie Beckett
   Katie Beckett in Georgia
Katie Beckett's Going Home
   (from People Magazine 1981)

Treatment or Cure
Canavan Pioneers
   *Gene Therapy
   Jacob Sheep Sensation
   Article in Forward-Jacob Sheep
   *Stem Cell Transplants
   Enzyme Replacement
   Substrate Inhibitors
   Should I Try Zavesca?
   Letter for Insurance 
      Approval for Zavesca
   Chaperone Therapy

In-Home Medical Care
Home Health Care
   Coping Strategies
Coping with Humor w/ Shui's Dad
Rachaeli's Story
Shocked by Tay-Sachs Article
The Project Shui Family
Mommy's Online Journal
   Abba's Online Journal
   Shui's Fun Pages


Return to top

Rachaeli started taking it at about 2 1/2 years of age, and has been taking it continuously for the past 5 years.  There are a number of issues regarding this medication, its side effects, and how they relate to the course of Infantile Tay-Sachs disease.  There are also many financial obstacles because of its cost.
--Should I Try Zavesca?
--Insurance Letter for Zavesca
Substrate Inhibition (Trickle-Down Therapy)



In most individuals the substrate (water) can be degraded efficiently by adequate enzyme (hole).

In affected individuals the amount of enzyme is insufficient to degrade the substrate and it accumulates.

In affected individuals treated with substrate synthesis inhibitors the amount of substrate is decreased to match the amount of residual enzyme to prevent accumulation.

Back to top
Substrate deprivation (also called substrate synthesis inhibition, substrate reduction, substrate balancing) is a biochemical approach that makes use of novel chemicals called inhibitors that decrease the production of the molecule that typically accumulates to high levels in persons with lysosomal storage diseases. For example, children with Tay-Sachs disease accumulate high levels of GM2 in brain cells and it is this accumulation which causes the brain cells to die. If one could decrease the synthesis of GM2, the substrate for the missing enzyme, then one would presumably decrease cell death and moderate the course of the disease.

The inhibitor Zavesca ® (miglustat), approved in Europe and the United States for the treatment of Gaucher Type 1, is in clinical trials in persons affected with Niemann-Pick Type C, and in children with juvenile GM2, Tay-Sachs and Sandhoff and in children under the age of 2 with Tay-Sachs and Sandhoff disease.

A three-year clinical trial of miglustat in persons affected with Late Onset Tay-Sachs disease ended in spring 2006, with unsatisfactory conclusions. Participants did not reach certain clinical endpoints that were part of the trial, such as improved muscle strength status, and Actelion, the drug company, decided not to file for an additional FDA indication for use with LOTS.

Studies with other substrate reduction compounds may occur in the future, and some affected individuals or parents of those affected do explore with their physicians the option of using this treatment on an “off-label” basis.


Back to top

From the Lysosomal Diseases of New Zealand Newsletter

This is just a part of an article written by a conference attendee in 2006.  It summarizes a panel discussion on Zavesca (Miglustat)

NTSAD 28th Family Conference April 6-9 2006

Alexandria, Virginia USA

Gina Murray was supported by the Lottery Grants board to attend her first ever National Tay Sachs Conference. Gina’s report follows.

*Medical and Research Update:

(The NIH/NINDS Workshop: Glycosphingolipids in Health and Disease was held 5-6 April at the same venue and we were fortunate to have the following presenters from that workshop.)

* BruceA. Bunnell PhD, (overview of current research efforts):

Caloric restriction along with gene therapy or stem cell therapy shows a lot of promise in delaying progression in neurodegenerative diseases. Appears to target CNS inflammation associated with ganglioside disorders.

* Paula Gregory PhD, (ABC’s of Genetics)

* Edwin Kolodny MD, Professor of Neurology NYU School of Medicine,

* David Korosec, RN,

* Gustavo Maegawa MD,

* Cynthia Tiff MD, PhD.

This session primarily focused on an update of Tay-Sachs and Sandhoff clinical trials of Zavesca (Migulstat).

The end point for these trials was stabilization in muscle strength but there was progressive deterioration in all patients from both the New York and Cleveland trials for LOTS. This is not to say that there wasn’t improvement in other areas. Anecdotal evidence showed an improvement in speech and stabilization of psychiatric symptoms.

Neutral study results thus far don’t sufficiently support in adult patients with LOTS but might benefit Early Onset and/or Juvenile Onset Tay-Sachs.

This session allowed for plenty of questions and informal discussion from the floor.

*Navigating off-label use of Zavesca:

A panel of parents who have successfully navigated the system for off-label use of Zavesca for their child (all pre school age). All of these children have the infantile form of the disease. Although Zavesca is not available in New Zealand as yet  I believe it was important to hear what these parents had to go through in order to get this drug for their children.

Some of the children are still on Zavesca and some have been taken off after several weeks mainly due to side effects such as severe diahorrea (which was also a huge problem for a lot of the teenagers and adults using Zavesca both on and off label).

These parents were unsure how Zavesca was working for their children as the nature of the disease is one of deterioration and was it Zavesca that was perhaps slowing things up or was it just the way the disease was progressing. There is really no answer to this.

**Rachaeli's parents were on this panel.  They were the only ones in favor of taking Zavesca

Back to top

Website Builder