NH- H4B Initiatives as of 12/31/16

  1. 2015, 2016, 2017: Sanford Medical Research and Exemplar Genetics is creating a porcine model with CLN2 disease. The goal of this project is to produce a novel pig model of CLN2 disease that recapitulates the human disease. We expect this will become a crucial research tool as more therapies for CLN2 disease become available for testing. NH-H4B have pledged up to $97.5 k over the duration of the three-year project.
  1. 2016: NH-H4B along with Drew’s Hope are funding Dr. Rebecca Whiting at the University of Missouri for a project titled, “Sustained TPP1 Enzyme Delivery for the Treatment of CLN2 disease Using Genetically Modified Autologous Stem Cells.”

This group will isolate cells from a CLN2 dog’s bone marrow and genetically modify them to produce large amounts of the enzyme. These cells will then be injected into the dog’s eye and into the fluid that surrounds the brain, where we expect they will remain and secrete the TPP1 enzyme, which will then be used by these tissues to function normally. This grant was for $35,000

  1. 2016: Dr. Jon Mink at the University of Rochester received $20,000 to link established natural history databases in order to have one international comprehensive and consolidated NCL natural history resource. Successful completion of these aims will provide essential clinical and biological information inform future valid, rigorous clinical trials in these devastating diseases.
  1. 2015 & 2016: Sponsorship of annual BDSRA family conference. Each year, $20k was allocated for conference in addition to $5k for the SIBS programing.

Total donations for 2 years= $50, 000

  1. 2015: Dr. Michelle Hastings at Rosalind Franklin School of Medicine and Science received $25k for her study, “Stop Codon Read-through and Nonsense Suppression for the Treatment of Infantile and Late-Infantile Neuronal Ceroid Lipofuscinosis (CLN2).
  1. 2015: Dr. Pahan at Rush University received $15.5k for the SCAR 7 project where he is trying to raise the TPP1 levels in these patients. Dr. Pahan is attempting to test the effects of Lopid, Tricor and Vitamin A in order to  naturally raise the production of TPP1.
  1. 2014: $35,000 postdoctoral fellowship by Dr. Yu Meng working in the lab of Dr. Peter Lobel at Rutgers University. Dr. Meng will continue her groundbreaking work on innovative and effective methods to deliver proteins across the blood brain barrier in Late Infantile Batten disease. If this work proves effective, it will allow the enzyme missing in Batten disease to be delivered via the bloodstream rather than via neurosurgery.
  1. 2014: As an extension of the previously funded Dem-Child database project by Dr. Schulz, funds will extend this project to analyze data to seek a large-scale retrospective chart analyses in a standardized manner, enabling us to look “back in time” and have this valuable data available for researchers and clinicians in the future.
  1. 2013: Helped co-fund a $153,000 project by Dr. Angela Schulz in Hamburg Germany who will be expanding the Dem-Child database network. This database will offer an on-line Batten disease patient registry for clinicians, researchers, and parents. Our funds will help expand the current database in Norway, Denmark, Turkey, France, Argentina, Brazil and the United States. The aim is to collect the world’s largest clinically and genetically best characterized set of Batten patient data.

The following are research initiatives that Hope 4 Bridget has helped make possible through donations from our fundraising efforts. This would not be possible without your help! Thank you for your continued support!

Upregulation of Cln2 by fibrate drugs
Dr. Kalipada Pahan, Rush University Medical Center, 24 months, $50,000
Start Date: May 2013

Batten Diseases comprise a group of genetic diseases that affect children. Children with these gene defects are missing key enzymes that help to break down waste products in brain cells. These waste products build up, and eventually destroy the brain cells. This causes a loss of function in these children, and eventually death.

This research team recently discovered that several already available and safe drugs can help brain cells produce more of the enzyme missing in the brain cells of children with Batten Disease. They have evidence that three commonly used drugs can cause healthy human and mice cells to produce more of that enzyme. The next step is to test these drugs in cells taken from actual Batten Disease patients, to see if it can have the same enzyme increasing effect.

If this study shows that Batten Disease cells will produce more of the enzyme when they come in contact with one or more of these drugs, we might finally have a safe, cost effective life-saving option to treat children with Batten Disease. This was made possible through our yearly fundraiser, A Fifth Season along with Noah’s Hope

Biomarkers for Measures of Short-term Success in Batten Disease Therapy
Dr. David Sleat, University of New Jersey, 12 Months, $100,000 (Hope 4 Bridget contribution, $33,000)
Start Date: 04/2013

Clinical trials for Batten disease include gene therapy, stem-cell transplant therapy, and small molecule therapies. Clinical trials are also planned for enzyme replacement therapy. The success of these trials is dependent on the ability to measure response to treatment to make sure patients are getting better on the right dose of therapy. Measuring response quickly will also accelerate approval of effective treatments and allow trials of ineffective treatments to be terminated in a timely manner.
The aim of this research is to identify effective biological molecules, called biomarkers, that will help measure the success of Batten research using mouse models. These biomarkers will show alterations in the brain that happen because of the Batten disease. Correction of the Batten disease will result in normalization of these brain changes. These studies will eventually move from the lab to the clinic. This research is also supported by the BDSRA and Beyond Batten Foundation.

Lysosomal Membrane Permeability in NCL Disease: Pathophysiology and Therapeutic Potential
Dr. Matthew C. Micsenyi, PhD – Postdoctoral Fellow
Dr. Steven U. Walkley, DVM, PhD – Laboratory Head
Albert Einstein College of Medicine, 12 months, $70,000 (H4B, $35,000)
Start Date: March 2013

The research team has done extensive studies that show that certain protective structures inside the brain cells of children with various Batten Diseases become leaky, releasing dangerous molecules into the brain cells. These molecules cause the brain cells to die. The team will study whether a drug developed for ALS can be repurposed to reduce the leakiness of these protective structures inside the brain cells, and therefore reduce the brain cell death in these children stricken with Batten Diseases. This is a one year study on mice models of two kinds of Batten Disease. The results could lead directly to the use of this repurposed drug in a clinical trial on Batten Disease patients. The study will be completed at the Albert Einstein College of Medicine in Bronx, New York.

Screening Drug Libraries for Efficacy in Stimulating Mutated CLN2 Genes (Batten Disease)
David A. Pearce, PhD, Sanford School of Medicine, 12 months, $45,000 ($16,00 from H4B)
Start Date: April 2012

Dr. David Pearce is working on a project which develops the methodology for using high-throughput screening assays in INCL and LINCL. High throughput screening uses advance robotics and technology to screen over 100,000 compounds to determine if there are any novel drugs that create new pathways of interest for treatment. It is a drug re-purposing project and one in which could be extremely helpful in finding an existing drug to aid in the treatment of Batten disease. The researchers propose a project to screen drug libraries for agents that show efficacy in stimulating the activity of mutated CLN2 genes in a defined cell assay.Some of this investigation includes:

• The Sanford Library, supplemented by other approved drugs, will be screened using the cell-based assay. The library will be screened at several drug concentrations, usually 10 mM and 100 mM.
• Drugs that appear to increase LINCL activity will be further studied using conventional dose ranging to determine effective doses and establish the reproducibility of individual drugs and combinations of drugs.
• Any drugs, compounds and combinations that appear to up- or down-regulate the production of TPP-1 will be further studied to provide further insight into mechanisms of the disease and pathways for abrogating the negative effects of the mutation.

A contribution from H4B in the amount of $25,000 was given to David Sleat, Associate Professor of Pharmacology, who works with Dr. Peter Lobel from the Center for Advanced Biotechnology and Medicine at Rutgers University. Their study focuses on creating a transgenic mouse that can withstand the human protein TPP1, which children with LINCL are lacking. Currently, the mice used in the experiment cannot withstand repeated dosing of the enzyme . If this experiment can be achieved, they can further their research of LINCL using repeated doses of the enzyme to treat and possibly cure the disease. It would be a significant breakthrough to achieve this.

Hope 4 Bridget assisted in the recruitment of seven other LINCL-Batten disease foundations to form a small working group dedicated to finding a treatment or cure for LINCL-Batten disease. A major event/ contribution was a Conference hosted by the National Institute of Health and the Batten Family Coalition. On November 11-12, 2010 about 50 people from around the world, representing the best from science, the industry, and the NIH came together in Bethesda, Maryland to discuss new approaches toward developing translational research for Infantile NCL and Late Infantile NCL (what Bridget has). The conference was a great success because it was the first time this group came together in an open discussion. We now look toward the future of research and trials in hopes that we can support these scientists and doctors. By coming together, they have opened the doors to one another and in finding a cure for our children.