Our New Expertise

After Noah and Laine were diagnosed with CLN2 Batten disease, we learned that there were multiple therapeutic approaches to CLN2 Batten disease. Although we did not have a laboratory background, we poured ourselves into the science of CLN2 Batten disease and became some of the leading experts on the disease. Noah’s Hope was therefore able to identify and fund research projects with the fastest potential for efficacy.

As a result of basic research funded by Noah’s Hope and other partners, and through continued engagement with our family, BioMarin Pharmaceuticals introduced the first drug therapy that could delay the onset of symptoms for CLN2 Batten disease in 2017, just one year before Laine passed away.

We are continuing our efforts to champion key research projects for CLN2 Batten disease. Some of the research projects that are being considered or explored around the world include the following.

Gene Therapy Research

How do cells and genes interact?

Cells are the basic building blocks of all living things; the human body is composed of trillions of them. Within our cells, there are thousands of genes that provide the information for the production of specific proteins and enzymes that make muscles, bones, and blood, which in turn support most of our body’s functions such as digestion, making energy, and growing.

What is gene therapy?

The genes in your body’s cells play an important role in your health—indeed, a defective gene or genes can make you sick. Over the past couple of decades, gene therapy has developed into a promising therapeutic treatment option for CLN2 Batten disease.

Recognizing this, scientists have been working for decades on ways to modify genes or replace faulty genes with healthy ones to treat, cure, or prevent a disease or medical condition.

Now this research on gene therapy is finally paying off. Since August 2017, the US Food & Drug Administration (FDA) has approved three gene therapy products, the first of their kind.

Two of them reprogram a patient’s own cells to attack a deadly cancer, and the most recently approved product targets a disease caused by mutations in a specific gene.

How does gene therapy work?

Sometimes all or part of a gene is defective or missing from birth, or a gene can change or mutate during adult life. Any of these variations can disrupt how proteins are made, which can contribute to health problems or diseases.

In gene therapy, scientists can do one of several things depending on the problem that is present. They can replace a gene that causes a medical problem with one that doesn’t, add genes to help the body to fight or treat disease, or turn off genes that are causing problems.

How do vectors work with gene therapy?

To insert new genes directly into cells, scientists use a vehicle called a “vector” which is genetically engineered to deliver the gene.

Viruses, for example, have a natural ability to deliver genetic material into cells, and therefore, can be used as vectors. Before a virus can be used to carry therapeutic genes into human cells, however, it is modified to remove its ability to cause an infectious disease.

Gene therapy can be used to modify cells inside (in vivo) or outside (ex-vivo) the body. When it’s done inside the body, a doctor will inject the vector carrying the gene directly into the part of the body that has defective cells.

In gene therapy used to modify cells outside of the body, doctors remove blood, bone marrow, or another tissue from a patient, and separate specific types of cells in the lab. The vector containing the desired gene is introduced into these cells. The cells are left to multiply in the laboratory, and are then injected back into the patient, where they continue to multiply and eventually produce the desired effect.

What happens before a gene therapy can go on the market?

Before a company can market a gene therapy product for use in humans, the gene therapy product has to be tested for safety and effectiveness so that FDA scientists can consider whether the risks of the therapy are acceptable in light of the benefits.

Gene therapy holds the promise to transform medicine and create options for patients who are living with difficult, and even incurable diseases. As scientists continue to make great strides in this therapy, we expect that the FDA will further it’s commitment to help speed development by promptly reviewing groundbreaking treatments that have the potential to save lives.

What is the new gene therapy for CLN2 Batten disease?

To date, gene therapy for CLN2 Batten has had two clinical trials in the United States using two different vectors. Both clinical trials were performed at the Weill Medical College of Cornell University. The first study used the AAV2 vector, and the second study used the AAVRh.10 vector.

On November 11, 2015, Spark Therapeutics, a Philadelphia-based biotech company scientifically co-founded with Dr. Beverly Davidson, announced their intention to explore gene therapy for CLN2 Batten disease. This announcement coincided with the release of the Davidson lab’s paper regarding the treatment of a CLN2 dog model with AAV2 gene therapy.

On March 16, 2016, Spark Therapeutics received Orphan Drug status for SPK TPP1 for Neuronal Ceroid Lipofuscinosis from the FDA.

What are small molecule therapies?

Several groups are currently researching small molecule (drug) therapies in CLN2 Batten disease using a number of approaches.

A Noah’s Hope – Hope4Bridget program to repurpose existing drugs is currently underway. We are now developing a partnership with the National Institutes of Health to determine the mechanism of action in some of the initial “hits” from a high-throughput drug screen we funded several years ago. With this project, we hope to find new clinical applications for already-approved drugs that can help children who have no time to wait.

One repurposing project that we began in 2010 is also moving forward. In May of 2010, Noah’s Hope reached out to a local scientist at Rush University in Chicago in hopes that some of his previous work might be applicable to CLN2 Batten disease.

After securing two rounds of funding for this project, and now with positive pre-clinical results, this work has been licensed by Polaryx Therapuetics. Polaryx is currently seeking partnerships and opportunities to move this potential therapy forward.

What are enzyme replacement therapies?

Enzyme replacement therapies have also been pursued heavily for the treatment of CLN2 Batten disease. As a previously proven therapy option in other lysosomal storage disorders (LSDs), enzyme replacement therapy represented so-called “low hanging fruit”.

The Noah’s Hope – Hope 4 Bridget Foundation previously partnered with the BDSRA to fund research that was in part used to develop the first-ever FDA-approved therapy for CLN2 Batten disease. Brineura (cerliponase alfa), is a recombinant TPP-1 enzyme replacement therapy marketed by BioMarin Pharmaceuticals, that was approved on April 27, 2017 by the FDA.

Brineura is approved to slow the loss of the ability to walk or crawl (ambulation) in symptomatic pediatric patients three years of age and older with CLN2 Batten disease.  The results of the multinational clinical trial that led to the approval of Brineura were published in The New England Journal of Medicine on May 17, 2018.

What are stem cell therapies?

Theoretically, stem cell therapies work in one of two ways: Either by the stem cells producing the missing enzyme, which can then be taken up by the enzyme deficient cells (cross-correction), or by the stem cell differentiating and replacing the person’s own (diseased) cells.

There have been trials involving both hematopoietic stem cells (cells from blood or bone marrow) and neural stem cells (nerve cells). Both types have been used in animal models and clinical trials.

Guide to Symptomatic Treatment of Neuronal Ceroid Lipofuscinosis

What has been the efficacy of hematopoietic stem cell therapy?

Hematopoietic stem cell transplantation has been used to treat CLN1 Batten disease, but while enzyme activity normalized in the white blood cells, activity remained low inside the brain (cerebrospinal fluid). The therapy had minimal effects on disease progression (Lonnqvist et al., 2001).

Hematopoietic stem cell transplantation has also been found to be largely ineffective against CLN2 Batten disease and CLN3 Batten disease (Lake, Steward, Oakhill, Wilson, & Perham, 1997).

What is the status of neural stem cell therapy?

This method works by getting stem cells to differentiate into nerve cells (neurons or glia cells). Animal trials have shown that the therapy works primarily through “cross-correction”, and that the therapy was able to delay loss of motor functions.

An open phase 1 trial on patients with CLN1 Batten disease and CLN2 Batten disease sponsored by now defunct Stem Cells Inc., proved that the method of transplanting neural stem cells directly into the brain’s cavities (lateral ventricles) with subsequent immuno-suppression was safe, but so far it has not been determined whether the therapy is effective (Selden et al., 2013). Post-mortem examinations of 3 patients found donor cells in 2 of them (Selden et al., 2013).

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