Leading the worldwide fight to treat and cure
Tay-Sachs, Canavan, GM1 and Sandhoff diseases

Helping Hand Grant Program

The Helping Hand Grant Program provides grants to families and individuals in-need to attend the Annual Family Conference. There are two ways to receive a grant:

1. Earn one free conference registration by selling $500 worth of raffle tickets for an adult registration (50 books), and $250 worth of raffle tickets for a children’s registration (25 books) by April 30, 2020.  Please note on the registration form if you are selling raffle tickets.

The Helping Hand Grant Program supports families through research, education, support, and connection at the Annual Family Conference. Buy a book (or books) of raffles to help support families’ conference experience and get the chance to win a cash prize of $1,000, $500 or $250! Please note the family who should receive credit for your purchase.

Ticket sales are only available online, using this link, here. If you’d like to print a note card to give out to let friends and family know where to purchase raffle tickets you can do so here. NTSAD 2020 Helping Hand Raffle.

2. The online Helping Hand Grant application will open in January of 2020, and you will be able to apply for conference attendance assistance (here with a link coming soon).  Only newly diagnosed and newly bereaved families will be considered for a grant after March 1, 2020. Apply early! Funds are limited!  If additional funds are available, grants will be considered through the end of April.

Our goal is to help as many families as possible. Please only request what is needed to make your attendance possible so we can help as many families as possible. Note: Travel is not covered.

Grant funds are only available  to cover conference registration and standard hotel rooms at the group rate $139/night (totaling $160/night with tax) during the conference; they may not be used for additional nights at the hotel or upgraded rooms. Travel will not be covered in 2020 due to the anticipated increase in requests this year. All Helping Hand Grant recipients are asked to fully participate in conference sessions.

Helping Hand Grant FAQs

Please keep in mind the following criteria:

ALL families are eligible to receive a Helping Hand Grant based on the limited availability of funds. 

What are the application funding limits?  Each application is reviewed by the Helping Hand Committee and each award is granted individually, but in general the guidelines for awards are as follows:

Newly diagnosed families/individuals attending for their first time:
$1200 Family/$600 Individual

Newly bereaved families attending for the first time:
$1200

Families/individuals who have attended the last few years:
$1000 Family/$500 Individual

Families/individuals who have received grants before:
$800 Family/$400 Individual

The following priorities are taken into consideration with each application, in the following order:

1) Limited to immediate family members and/or primary caregivers of the affected only.

2) Newly diagnosed families and individuals that have connected with NTSAD since the last Conference;

3) Families and individuals who are newly bereaved and grieving within the past year;

4) Families and individuals who have not previously attended an annual conference;

5) Families and individuals who actively raise funds for the Helping Hand Grant and NTSAD programs;

6) Families and individuals who are actively engaged as NTSAD community members.

7) Families and individuals that have received a grant for three years in a row will not be eligible for a grant the following year unless they become newly bereaved that year.

Buryk Fund Finances Research Grants

The Katie & Allie Buryk Research Fund has financed research grants in 2015, 2016 and 2017.

NTSAD Research Initiative Grants supported by the Katie & Allie Buryk Research Fund  

2017

Grant funded for research project “Accelerated program for CSF delivery of AAV gene therapy for Tay-Sachs and Sandhoff patients”

Principal Investigator: Miguel Sena-Esteves, PhD, University of Massachusetts Medical School

While intracranial injection of AAV vectors is the most advanced gene therapy for Tay-Sachs and Sandhoff diseases, the current approach involves two vectors encoding separately the hexosaminidase A (HexA) alpha- and beta-subunits, which are injected bilaterally in the thalamus and one cerebral lateral ventricle. There are drawbacks to this approach, such as the invasiveness of direct injections into the brain that require a neurosurgical procedure, and its use of two AAV vectors which double the costs of manufacturing and an eventual treatment. After much initial work, there are now single AAV vectors carrying both subunits that show promising results in GM2 mice. These new vectors can enter the brain effectively after injection into the bloodstream, or injection into the cerebral spinal fluid (CSF). Presently it is unknown which approach will be the most effective and therefore it is important to test both.

To date, ongoing studies testing bloodstream delivery of these new AAV vectors in GM2 mice have shown very promising results. This project will focus on the delivery of AAV vectors to the central nervous system through CSF administration (e.g. intrathecal space) which has several advantages to treat Late Onset patients. The funding will primarily support a research associate to conduct mouse studies related to CSF delivery of AAV9 vector in GM2 mice including generating mice, injections, behavioral studies, histological and biochemical analyses of tissues post-mortem.

Minimally invasive delivery of AAV gene therapy in the Tay-Sachs Sheep

Principal Investigator, Heather Gray-Edwards, PhD, Scott-Ritchey Research Center, Auburn University, Auburn, AL


Goals of the Proposal

  • To evaluate efficacy of adeno associated viral (AAV) gene therapy after cerebrospinal fluid (CSF) delivery in the sheep model of Tay-Sachs disease (TSD)
  • To confirm previously proposed biomarkers of TSD, including MRI image, lipidomic signatures, cognitive testing, and neurologic evaluation
  • To study the biodistribution and clearance of CSF delivered AAV gene therapy in the Tay-Sachs sheep

Impact of Research
Gene therapy, is one of the most promising treatment options in development. The study will evaluate the efficacy and biodistribution of the state-of-the-art gene therapy in TSD sheep. Tay-Sachs sheep is one of the most relevant animal models of the disease, due to its large brain size and suitability for various biomarker studies.

The findings in this proposal will aid in expanding our knowledge on the treatment’s administration and biodistribution. The efficacy profile from the work with be necessary and helpful for future regulatory application before FDA. Most importantly, this study will generate useful data and insight about TSD biomarkers and contribute to future clinical studies in human patients.

Amendment to complete safety study in non-human primates 

Principal Investigator: Miguel Sena-Esteves, PhD, University of Massachusetts Medical School

2016

Identifying Novel Therapeutics for Treating GM2 Gangliosidoses 

Principal Investigator: Beverly L Davidson, Ph.D., Children's Hospital of Philadelphia (CHOP)

The drug Miglustat (approved for Gaucher disease in 2002) does not cross the blood-brain barrier to an extent that could mediate benefit in a clinical trial in patients with late onset Tay-Sachs disease. In this study, they are using a powerful drug discovery approach to identify FDA approved drugs that have improved brain penetrance while simultaneously share the same efficacy as Miglustat. 

They have submitted 49 samples to the University of Iowa, Genomics division for high-throughput RNA-sequencing. These samples represent 7 donors treated with the three drug treatments and controls at two different doses. 

Next Steps: They will query the LINCS database with the RNA-seq data, identify drugs and validate hits over the next 4-6 months. Importance: These important preliminary studies will help identify additional, brain penetrable drugs that may find use in substrate reduction therapy for the gangliosidoses. 

Clinically Relevant Outcome Measures for Patients with Late Onset Tay-Sachs disease Ascertained Real-Time Through Patient Wearable Technology

Principal Investigator: Cynthia J. Tifft, MD, PhD, National Human Genome Research Institute, National Institutes of Health

This proposal is a next step in identifying relevant outcome measures for clinical trials. Considerable data on the late onset Tay-Sachs (LOTS) and Sandhoff (LOSD) patients has recently been collected at two sites (Massachusetts General Hospital and the NIH Clinical Center) as well as the last two NTSAD Annual Family Conferences and this exploratory study would expand the range of outcomes to metrics relevant to the daily lives of LOTS and LOSD adults, including their ability to move about and participate in the activities of daily living.

This is a 6 month exploratory study using 5-8 ambulatory or partially ambulatory adult patients with late onset Tay-Sachs or Sandhoff disease to collect patient data on ambulation, falls, and wake/sleep cycles and other patient input that can be tested as clinically relevant outcome measures for future clinical trials.  Data is collected through a wearable device and transmitted through a mobile app to Dr. Tifft for analysis.  The data collected will be compared to clinical testing including gait lab metrics to be conducted at the NIH Clinical Center at the time of initial evaluation and at the 6 month endpoint.

2015

Late Onset GM2 Gangliosidoses Registry and Repository
Principal Investigator: Florian S. Eichler, MD, Massachusetts General Hospital

This project aims to develop a both a clinical registry and a repository of samples for Late Onset GM2 Gangliosidoses. The registry will use the NeuroBANK platform to create and implement use of electronic case report forms, allowing standardized data to be collected from patients with LOTS. Review of current medical literature and surveys of patients will help determine which data to include in the registry in order to establish meaningful outcome measures. Prospective evaluations of patients will also be used to determine these optimal outcome measures, looking at change over time, patient value of measures, and variability among patients. Samples collected will be used to identify potential biomarkers of disease progression and to correlate these biomarkers with clinical outcomes. Both clinical outcome measures and biomarkers are essential components of clinical trial readiness, necessary to show effect of any experimental therapy.

Generation of a knock-in mutant Hexbmouse model
Principal Investigator: Eric R. Sjoberg, PhD , OrPhi Therapeutics

This project supports the development of a mouse model for Late Onset Tay Sachs and Sandhoff diseases. Mice with Sandhoff disease are used to study both diseases because both store GM2 gangliosides and because mice with mutations in the HEXA gene which causes TSD do not develop features of TSD due to an alternate pathway for GM2 degradation. This model is different from currently existing SD mouse models in that it has a specific mutation that leads to residual enzyme, as is seen in the late onset forms of these diseases in humans. This new model will be used to study pharmacological chaperones, small molecules that can bind and stabilize mutated enzyme. This allows the misfolded enzyme to reach the lysosome and degrade stored material correctly. The two chaperones that will be studied have been previously shown to increase both HexA and HexB enzyme in healthy mice. The project will look for increased enzyme activity and reduced ganglioside storage in the brain. The mouse model will also be made available for other late onset research.

About the Katie & Allie Buryk Research Fund

After being diagnosed with Late Onset Tay-Sachs disease, Katie Buryk and her family established a fund to raise money for research for a cure.  Read more: Katie & Allie Buryk Research Fund

Seventh Annual 'Fore' Jack Memorial Golf Outing

Jack Alan Kliger was diagnosed with Canavan Disease when he was nine months old. Jack was given a life expectancy of three to five years. Jack passed away in April 2008 just shy of his 14th birthday.

Throughout his short life his family received support and encouragement by being part of the larger family of NTSAD and its members whose children fought similar diseases and similar battles. NTSAD offers parents information, explanations and resources as well as heartfelt support.

Your support will help NTSAD with their goal to eradicate Canavan, Tay-Sachs and similar diseases and also to help the children afflicted with these diseases and their families cope with the pain and suffering associated with these diseases.  

Register for the Seventh Annual Jack Kliger Memorial Tennis & Golf Outing here.

2015 Research Initiative Grants

NTSAD has solicited proposals for basic, translational or clinical research projects. The 2015 grants include projects related to newborn screening, gene therapy delivery methods, animal models and international patient registries.

View Press Release (.pdf)


Denis C. Lehotay, PhD, Principal Investigator
Queen's College, Kingston, Ontario

Development and validation of a rapid,
MS/MS-based method 
to detect
Hexosaminidase deficiency in Tay-Sachs disease

Goals of the Proposal

  • Validate an existing high through-put MS/MS method for detection of reduced hexosaminidase activity (that was developed for Sandhoff disease) using dried blood spots (DBS) in normal patients and patients affected with Tay-Sachs disease (TSD).
  • Determine hexosaminidase activity in 1000 de-identified DBS from normal patients and in 10-20 samples from known TSD patients to establish reference ranges and cut off values.
  • Conduct a pilot-screening study using ~5000 DBS from an area of Quebec with high carrier frequency (~1/25) among French Canadians, which is similar to that found among Ashkenazi Jewish populations.

Impact of Research

Once treatment for TSD becomes available, detecting TSD by early screening, including newborn screening, and initiating early treatment will become essential to preventing the devastating consequences of this currently incurable condition. Developing, validating, and testing a rapid MS/MS based assay for measuring hexosaminidase activity in populations with a high incidence of the disease are part of the essential steps that will lead to an established newborn screen and an eventual cure.


Douglas R. Martin, PhD, Principal Investigator
Auburn University

Project: Intravascular gene therapy for
feline GM2 gangliosidosis

Goals of the Proposal

  • Optimize intravascular (IV) gene therapy to treat both central nervous system (CNS) and peripheral (rest of body) manifestations of feline Sandhoff disease (SD).
  • Conduct short-term (6 week) studies to compare different delivery routes (i.e. carotid artery and cephalic vein) for optimal therapeutic effect in the CNS and minimized vector levels in the periphery.
  • After selecting optimal delivery route, the therapeutic effect of pretreating cats with mannitol to temporarily open the blood brain barrier and possibly permit use of a lower dose of vector for long-term therapy will be evaluated.

Impact of Research

NTSAD has previously supported efforts of the Tay-Sachs Gene Therapy Consortium to develop an effective gene therapy protocol for TSD and SD. Previous studies with direct intracranial injection of Adeno-associated virus (AAV) vectors expressing hexosaminidase dramatically increased the life span and quality of life in SD cats. While these proof-of-concept studies continue to support human application of intracranial gene therapy for TSD and SD, it is desirable to develop a less invasive and presumably safer approach that will also better address peripheral disease.


Heather A. Lau, MD, MS, Principal Investigator
Paola Leone, PhD, Co-Investigator
New York University
The Canavan Foundation, Co-funder

Project: Defining the Natural History of Canavan Disease
through Development of an International Registry

Goals of the Proposal

  • Create an international electronic database to gather data prospectively in order to enhance the understanding of clinical variability, further define the relationship between genotype and phenotype, and delineate the progression of natural history of patients with Canavan disease (CD).
  • Maintain a bio-repository of blood and urine specimens collected from CD patients for potential evaluation of biomarkers.
  • Provide the medical community treating patients with CD with recommendations for monitoring and managing patients in order to optimize patient care.
  • To define and categorize clinical endpoints that may be used for the development of clinical therapeutic trials.

Impact of Research

A disease registry is integral to elucidate the natural history of the disease and its varied clinical presentations so that appropriate clinical endpoints are obtained to show efficacy of potential therapies. These efforts will also harmonize the efforts of Dr. Annette Bley at the University Medical Center Hamburg-Eppendorf, Dr. Florian Eichler at Massachusetts General Hospital, and other clinical sites around the world to increase the power of individual studies.



The following two grants are made possible by the Katie & Allie Buryk Research Fund of NTSAD:

Florian S. Eichler, MD, Principal Investigator
Massachusetts General Hospital

Project: Registry and Repository for
Late Onset GM2 Gangliosidoses

Goals of the Proposal

  • Perform a comparative review of literature reports and patient surveys for natural history data and outcome measures to establish an inventory for TSD with participation from various sources.
  • Determine optimal outcome measures in LOTS patients through a prospective pilot project at MGH. Outcome measures will be judged based on variability of data, change over a 6-month period, and patient ranking of importance.
  • Create and implement electronic case report forms based on outcome measures to allow several centers to participate in future trials using NeuroBANK.
  • Perform prospective studies of longitudinal outcome measures and biomarkers in LOTS patients.

Impact of Research

This proposal will retrospectively and prospectively determine optimal outcome measures in LOTS patients and thereby assist in protocol development and trial design. Specifically, this proposal will identify the target population and clinical endpoints in the LOTS subpopulation of the disorder and will be vital in responding to questions of patients, families, medical practitioners, industry and regulatory bodies alike.


Eric R. Sjoberg, PhD, Principal Investigator
OrPhi Therapeutics

Project: Generation of a knock-in
mutant Hexb mouse model

Goals of the Proposal

  • Create a specific missense point mutation in the beta chain of hexosaminidase that can be rescued by pharmacological chaperones, small molecules that selectively bind and stabilize certain point mutations, in order to test efficacy of chaperones that are being developed for Late Onset Tay-Sachs and Sandhoff disease.
  • Compare brain levels of beta-hex, GA2, and GM2 levels in disease-causing homozygous knock-in mice to determine if a biochemical phenotype similar to Late Onset Tay-Sachs and Sandhoff diseases presents in the mouse model.

Impact of Research

Pharmacological chaperones represent a new class of treatment for patients with diseases that result from destabilization, unfolding, or misfolding of a protein. The current GM2 mouse model is a hexosaminidase knock-out (hex-/-), which does not produce any of the target protein and therefore cannot be used to evaluate various chaperones ability to bind and stabilize the protein. Creation of a knock-in mouse with a point mutation, which is equivalent to a known human late onset mutation, will allow analysis of in vivo dosing effects of specific chaperones that have already been developed. The mouse model will be made available for other late onset research.

 

Help Fund Research

Each year research and advances in technology brings us a little closer to finding a cure for allied diseases including Tay-Sachs, Canavan, Sandhoff and GM1. We need your help to continue the efforts.  Please contribute to the cause.

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