Nickolas TJ DuVall Fund
- Last Updated: Friday, 29 May 2015 16:25
Two weeks ago my family and I sat through the Audubon High School commencement ceremonies. Normally this would be one of a parent’s proudest moments. But for us it was a day of sadness, a day of what could have been. For this is the year which should have been Nicki’s graduation had he not succumbed to Tay-Sachs Disease before he had the opportunity to even start school.
Graduation is a milestone event for parents. We look back and celebrate all of our children’s accomplishments. As well, we look forward to our child’s future. The world is theirs to change. Certainly Nick had a tremendous impact on all who came into his world. He taught lessons like:
Life is short; seize the day.
Enjoy the beauty of the simple things:
a breeze in your hair, birds singing, simple touch.
Love with all you have-with no expectations in return.
Forgive and reconstruct broken relationships.
Although his life was complete in 3 short years, having accomplished all he came to accomplish, we found ourselves grieving 2 things that day as we sat in the stands. First we grieved that he was not known. Many who filled the stands that day did not realize there was a beautiful soul that should be filling one of those chairs on the floor. Secondly we longed for him to have an impact on the future, a purpose, significance beyond those 3 short years.
That longing is what has brought us to write this letter. We are asking you to help us celebrate Nick’s memory and greatness. We are also seeking your support to help us make a significant impact on the future in his honor. You see we are not the only parents in this situation. We have personally known 161 other children who will not graduate due to Tay-Sachs or other related diseases. We are in dire need of funding for research. Join us in a monetary gift to National Tay-Sachs and Allied Diseases in honor of Nickolas. Together we will fight to cure these diseases until they no longer steal the futures of our children.
The Du Valls,
Joel, Rhonda, Samie, Nicki, and Teddy
Despite being characterized over 100 years ago, to date there remains no treatment or cure for Tay-Sachs disease. Several therapeutic approaches are being researched and open label use (approved by FDA for other diseases but not Tay-Sachs) clinical trials are ongoing. Most common approaches include: enzyme replacement therapy (ERT) which delivers a healthy form of the defective enzyme, substrate reduction therapy (SRT) which reduces synthesis of the molecule that cannot be broken down, and chaperone therapy which uses a small pharmacological molecule that can interact with the mutant protein to restore its original conformation and function. ERT has become the standard of care for some LSDs, such as Type I Gaucher disease (5), in which there is no CNS disease. However, the inability of large proteins to cross the blood brain barrier (BBB) and enter the brain renders this therapy ineffective for neurologic LSDs such as Tay-Sachs disease.
A 2009 Research Initiative grant from NTSAD was administered to Dr. Joe Clarke to support an open-label Phase I/II clinical trial of pyrimethamine, a pharmacological chaperone, for the treatment of patients affected with Tay-Sachs or Sandhoff disease. This clinical trial evaluated the tolerability of pyrimethamine by patients and the effectiveness of the molecule in raising Hex A levels in blood in a small number of patients. The study found that Hex A level was increased up to 4-fold in people taking 50 mg or less of the medication each day. When the dose was increased to 75 mg per day or higher, most participants had significant side effects, including worsening problems with coordination. The full publication can be viewed here.
A clinical trial to evaluate the safety and efficacy of SRT using a drug called migulstat (brand name Zavesca) has also been conducted for Late Onset Tay-Sachs. Miglustat did not result in any measurable clinical benefit in the 20 late onset patients given 200 mg orally three times a day when compared to patients that did not take miglustat. Prominent side effects of the drug were weight loss and diarrhea (6), as this drug also effects the ability to digest complex carbohydrates. It remains unclear whether earlier treatment in more mildly affected patients would result in benefit. There are reports of benefits to individual patients with Tay-Sachs disease treated with miglustat (7, 8), and further studies are warranted if coupled with detailed natural history studies to allow better interpretation of the outcomes of the trial. The NTSAD Scientific Advisory Committee (SAC) subcommittee on experimental therapies recently reviewed the data regarding miglustat’s safety and potential efficacy.
The Tay-Sachs Gene Therapy Consortium, formed from a collaboration with NTSAD and researchers from the U.S. and the U.K., is focused on developing gene therapy approaches to all forms of Tay-Sachs disease. These studies are still in the pre-clinical phase and safety studies must be completed before clinical trials can be initiated.
1. M. Fuller, P. J. Meikle, J. J. Hopwood, in Fabry Disease: Perspectives from 5 Years of FOS, A. Mehta, M. Beck, G. Sunder-Plassmann, Eds. (Oxford, 2006).
2. P. J. Meikle, J. J. Hopwood, A. E. Clague, W. F. Carey, Prevalence of lysosomal storage disorders. JAMA 281, 249-254 (1999); published online EpubJan 20 (joc80368 [pii]).
3. S. Sanderson, A. Green, M. A. Preece, H. Burton, The incidence of inherited metabolic disorders in the West Midlands, UK. Archives of disease in childhood 91, 896-899 (2006); published online EpubNov (10.1136/adc.2005.091637).
4. A. E. Bley, O. A. Giannikopoulos, D. Hayden, K. Kubilus, C. J. Tifft, F. S. Eichler, Natural history of infantile G(M2) gangliosidosis. Pediatrics 128, e1233-1241 (2011); published online EpubNov (10.1542/peds.2011-0078).
5. A. Zimran, D. Elstein, Management of Gaucher disease: enzyme replacement therapy. Pediatric endocrinology reviews : PER 12 Suppl 1, 82-87 (2014); published online EpubSep (
6. B. E. Shapiro, E. L. Logigian, E. H. Kolodny, G. M. Pastores, Late-onset Tay-Sachs disease: the spectrum of peripheral neuropathy in 30 affected patients. Muscle Nerve 38, 1012-1015 (2008); published online EpubAug (10.1002/mus.21061).
7. B. Bembi, F. Marchetti, V. I. Guerci, G. Ciana, R. Addobbati, D. Grasso, R. Barone, R. Cariati, L. Fernandez-Guillen, T. Butters, M. G. Pittis, Substrate reduction therapy in the infantile form of Tay-Sachs disease. Neurology 66, 278-280 (2006); published online EpubJan 24 (10.1212/01.wnl.0000194225.78917.de).
8. M. Masciullo, M. Santoro, A. Modoni, E. Ricci, J. Guitton, P. Tonali, G. Silvestri, Substrate reduction therapy with miglustat in chronic GM2 gangliosidosis type Sandhoff: results of a 3-year follow-up. J Inherit Metab Dis 33 Suppl 3, S355-361 (2010); published online EpubDec (10.1007/s10545-010-9186-3).
The 2020 Annual Family Conference will be held at the Renaissance Denver Stapleton Hotel, from Thursday, May 28 to Sunday, May 31, 2020. A gift of sponsorship is a wonderful way to support the conference experience, the families, their children and the adults affected by these rare genetic diseases. All sponsorships will receive recognition and a token of our thanks after the conference.
Ways to Sponsor
The Ways Your Gifts Help at the Conference
Caring for the Children
Caring for the Family
It’s All About Research
It’s in the Details
|Make your sponsorship gift online here -or- pdf mail this form (418 KB) . Please note what you would like to support. Please contact NTSAD 617) 277-4463 if you have questions.|
This is Xavier. He has a very rare and degenerative genetic disease called Sandhoff disease. He is an incredible little man who just turned 7 years old in November.
Since we learned of his diagnosis, we have been making the best of it with the support of our family and friends. He is still attending Silver Creek Pre-school - a school that serves children with physical and developmental challenges. He has a wonderful time with his classmates, doing crafts, music and many other fun activities, which has been incredible for him and our whole family.
You can follow this story on his Facebook page: https://www.facebook.com/forXavierSilva?pnref=story
We are updating this page for a 2nd Hair Cutting Fundraising event. It’s been over 3 years….and I’m due for a shearing. This is inspired by Xavier having a haircut of his own this week….and well, let’s just say my wife isn’t particularly thrilled at being married to a Sasquatch. (Here is a video montage of the last event https://www.facebook.com/forXavierSilva/videos/679733048819782/)
This is inspired by Xavier having a haircut of his own this week….and well, let’s just say my wife isn’t particularly thrilled at being married to a Sasquatch.
Please donate if you can. Share this page with all of your friends and families.
Watch this page and Xavier's Facebook page to stay in touch.
Thank you so much for your support and standing with us as we celebrate my son every day.