History of Batten disease

Four children with probable Juvenile Batten disease were first described by Otto Christian Stengel, MD, in 1826.80 He noted that four siblings developed normally until each began to lose their sight around six years old leading to blindness followed by progressive mental decline, loss of speech, seizures and death. The disease, however, is named after Frederick Batten, MA, MD, FRCP, when he reported almost 100 years later on two sisters with vision loss, neurocognitive decline and motor problems separating it from recently discovered Tay-Sachs disease and macular degeneration. 3,4

 

Juvenile Batten disease

Juvenile Batten disease is one of a group of disorders known as neuronal ceroid lipofuscinoses (NCLs). Over 400 different errors (mutations) in 14 segments of DNA (genes) have been attributed to various forms of Batten, which differ from one another primarily by when symptoms first appear.11,57,59,61 These disorders all affect the nervous system with increasing seizures, movement disorders, altered thought processes, and cognitive decline. Childhood NCLs also include vision loss but adult onset Batten typically does not.6,8,22, 33,63,77 Although Batten disease was originally used to describe only the juvenile form, the term “Batten disease” is widely used to refer to all forms of NCL.

 

The CLN3 gene

Juvenile Batten disease results from mutations (mistakes) in the CLN3 gene (blueprint) responsible for making CLN3 protein. More than 60 different mutations in the CLN3 gene have been shown to cause juvenile Batten disease.89 However, most children with the disease are missing the same string of 966 DNA building blocks from the CLN3 gene; this mutation is known as the “1kb deletion.” The effects of the deletion are not well-understood. Click here for more information on the CLN3 gene and its protein.

 

Batten disease and other NCLs are linked to a buildup of substances called lipofuscins (lipopigments) in the body’s tissues. These lipopigments are made up of fats and proteins. Their name comes from the technical word “lipo,” which is short for lipid, or fat, and from the term “pigment,” used because they take on a greenish-yellow color when viewed under an ultraviolet light microscope. The lipopigments build up in brain cells as well as in skin, muscle, and many other tissues. Inside the cells, these pigments form deposits with distinctive shapes that can be seen under a more powerful electron microscope. All NCLs form deposits. JNCL deposits which look like fingerprints. Healthy lysosomes regularly dispose of these lipofuscins just as they recycle and get rid of other cellular wastes.

 

Many cells in the body contain CLN3 protein: skin cells (the cells that are biopsied for diagnosis), muscle cells, kidney cells, liver cells, etc. However, these cells don’t die from having malformed or absent CLN3 protein, and it’s unclear whether they’re affected by all of that material that builds up. So why are neurons so harshly – and uniquely – affected?

 

Neurons have advanced communication skills. They communicate information through both chemical and electrical signals via specialized structures called axons and dendrites. We aren’t sure why neurons are selectively affected, but we know that these cells are particularly susceptible to damage when their recycling centers fail to work properly, which occurs in many neurodegenerative diseases like JNCL, the other NCLs, and over two-thirds of the 50 lysosomal storage diseases. Although the genetic basis for many of these diseases is clear and some of the biochemistry of missing or affected proteins is well understood, the cellular mechanisms by which deficiencies in these proteins disrupt neuronal viability remain ambiguous. One analogy is to think of neurons as the Lamborghini of cells, capable of providing high performance but delicate.

 

Research Progress

For over 100 years, researchers have been investigating the cause and mechanism of Juvenile Batten disease. Until 1995 when the genetic culprit, the CLN3 gene, was located, progress was quite slow.31 By the late 1990s, rapid technological advances in the development of small animal models and molecular biology techniques aided research efforts and helped to add significant knowledge to our understanding of the disease.

 

We need to capitalize upon new knowledge and advanced technologies being applied to other neurodegenerative diseases like Alzheimer’s disease and Parkinson’s disease. We must recruit the best and brightest from our nation’s 172 medical schools and 261 doctoral programs as well as Pharmaceutical Industry experts and scientific thought leaders from around the world. We must provide them with salary support, specialized training, seed money and technological resources that open the door to even greater opportunity. We need to build upon the following advances:

 

1995

  • The International Batten Disease Consortium comprised of 27 investigators across 9 academic institutions work together to locate the CLN3 gene responsible for JNCL and discover that CLN3 encodes a 438 amino acid transmembrane protein.31

1997

  • Investigators at the University College London Medical School determine the DNA alphabet of the CLN3 gene, critically important for determining its function.58

1998

  • Researchers demonstrate that the CLN3 protein is located in lysosomes, or the recycling centers of the cell, which leads to the classification of Juvenile Batten disease as a Lysosomal disease.32

1999

  • A function of CLN3 protein is reported to be to prevent neurons from being destroyed via programmed cell death, a natural mechanism used by the body to rid itself of damaged cells.68
  • Investigators create a mouse that is missing the CLN3 gene, hoping its absence in the animal will provide important clues to its function in humans.56

2001

  • CLN3 protein is found in vesicles along neuronal processes and synaptic vesicles filled with neurotransmitters, the chemicals that neurons use to communicate.49

2002

  • Researchers in Boston, MA, create a mouse with the same genetic defect in its CLN3 gene that most children diagnosed with JNCL have. They use this mouse to show, for the first time, that the disease begins its course even before birth.20

2004

  • CLN3 protein is eventually found in multiple compartments of the cell beyond lysosomes and synaptic vesicles (endosomes, plasma membrane, and Golgi bodies), suggesting CLN3 protein plays a role in the processing, packaging, and possibly transporting of molecules through the cell for disposal or recycling.44,66
  • Researchers find that in the early stages of the disease, certain groups of brain cells are affected much more than others, including those involved in motor activity and movement. This selectivity does not appear to be directly related to the amount of undigested material in the lysosome.57
  • Discoveries about the interactions between the CLN3 protein, microtubule-binding protein Hook1, and Rab GTPases suggest a link between CLN3’s function, the skeleton of the cell, and how cells absorb molecules from the outside (endocytosis).50
  • Trafficking and mitochondrial abnormalities precede ATP synthase subunit C accumulation in a cell model of JNCL suggesting JNCL is more than “cellular indigestion.”24

2005

  • Using the JNCL mouse model, which has a form of CLN3 that is genetically identical to the one found in affected humans, investigators show that these animals exhibit regional atrophy and glial reactions providing the first direct evidence that JNCL deficits are localized.67
  • Investigators at the University of Rochester publish a clinical rating instrument to assess the motor, behavioral and functional capacity of children over the course of the disease.54

2006

  • Autophagy, a cell’s ability to recycle its own contents, is disrupted in the JNCL mouse model with the same genetic defect as most children with JNCL.9
  • Following up on their work published in 2004, Luiro and colleagues carried out comparative analyses of cell cultures derived from CLN3 -/- mice missing the CLN3 gene and showed that in the absence of CLN3 protein, mouse neurons exhibit abnormalities in the microtubule cytoskeleton as well as microtubule-binding protein Hook1, mitochondrial dysfunction, and neuron-specific synaptic dysfunction suggesting a link between CLN3 protein and cytoskeleton-mediated neuron-specific function (presynaptic inhibition).48
  • Samples obtained from patients with JNCL and mice that do not make CLN3 protein accumulate autoantibodies to GAD65 and other brain-directed antigens in their blood suggesting that autoimmune disease is a primary or secondary effect of JNCL and this effect is dissimilar to autoimmune disease found in Stiff Person Syndrome and Type I Diabetes in which GAD65 autoantibodies are also elevated.46

2007

  • Investigators experimentally determine that Calsenin/DREAM/KChIP3, a neuronal Ca 2+ multifunctional binding protein may interact with CLN3 protein during one or more of its functions and the loss of Calsenin/CLN3 interactions may mediate cell death.16
  • Deficiency of CLN3 protein results in altered lipid composition of cell membranes as evidenced by decreased bis(monoacylglycerol)phosphate (BMP) biosynthesis. Similar to other cellular dysfunctions found in JNCL, it is unknown whether reduced BMP biosynthesis is primary or secondary to disease. Regardless, each piece of evidence leads to clues as to establishing the true role(s) of CLN3 protein.30

2008

  • While CLN3 protein’s function is still a “black box” in many ways, much is known about cellular functions disrupted by the loss of normal CLN3 protein. Evidence for CLN3’s involvement in lipid metabolism includes its localization to Golgi/Rab4-/Rab11-positive endosomes and lipid rafts and its galactosylceramide (GalCer) lipid raft-binding domain. 71
  • Investigators demonstrate that CLN3 protein interacts with plasma membrane-associated cytoskeletal and endocytic fodrin and the associated Na+, K+ ATPase complex suggesting that CLN3 protein is involved in the regulation of the cellular skeleton and non-pumping functions of Na+, K+ ATPase which may play a role in neuronal degeneration.85

2009

  • Altered arginine metabolism defects originally discovered using a yeast model are confirmed in CLN3-deficient mice.13
  • Applying computationally intensive techniques to existing data sets, investigators in Naples Italy publish their discovery of Transcription Factor EB (TFEB) in Science, one of the top 1% of 28,000 scientific journals. TFEB increases the number of lysosomes in a cell and therefore could potentially rescue JNCL cells by making them more efficient.72
  • Due to the therapeutic potential of TFEB, Beyond Batten and Cherie and Jim Flores provided Texas Children’s with a $2.5 million gift to bring this group over to Texas Children’s and Baylor College of Medicine. This is the largest hospital and clinical research campus in the United States, home to some of the brightest minds in the world, with access to stellar resources. This was also the largest single research award in JNCL research. http://beyondbatten.org/media-coverage/paving-the-path-to-prevention-2-5-million-gift-brings-world-famous-researcher-to-texas-childrens/

2010

  • Proteomics or the large scale study of proteins, the main components of cellular processes, together with computerized technology was used to identify the interaction network in human cells necessary for autophagy or intracellular recycling revealing a network of 751 interactions among 409 protein candidates including CLN3 protein. Upon closer examination it was revealed that CLN3 protein may interact with as many as 30 other proteins. 5
  • Investigators show that CLN3 mutations result in different courses of disease as determined by the Unified Batten Disease Rating Scale, a clinical tool that examines motor, behavioral and psychological symptoms over time. 1,45
  • Recent advancements reprogramming JNCL skin cells into induced pluripotent stem cells into neurons allows researchers to study the disease from the very beginning, years prior to the development of clinical symptoms.18,47

2011

  • Immunosuppression alters disease severity in mice missing the CLN3 gene, suggesting immunomodulation may represent a possible treatment strategy.75
  • Using an in vitro (cell culture) model of JNCL, investigators show that Lithium, which exerts therapeutic effects in a variety of neuronal disease models for stroke and Huntington’s disease and clinical disease such as bipolar disease, rescues the impaired cellular recycling program in JNCL mouse model cells and reduces disease-specific neuronal cell death.15
  • Investigators examined cell lines derived from animal models of variant late-infantile NCL caused by CLN6 mutations and JNCL caused by CLN3 mutations to learn that CLN6 and CLN3 mutations trigger distinct processes that converge on a shared pathway.10
  • Investigators find six calcium channel modulators capable of lowering calcium levels inside JNCL cell models. Calcium dysregulation, occurring in JNCL, has been linked to synaptic dysfunction and cell death.2
  • Scientists continue their initial work on examining cardiac involvement in JNCL.64
  • Scientists in London use a fruit fly model to show that a lack of functional CLN3 protein leads to a failure to manage oxidative stress which may be a key deficit in JNCL that leads to neuronal degeneration.83
  • Altered excitotoxic glutamate receptor activity suggests that AMPA and NMDA glutamate receptors are potential therapeutic targets in JNCL.23
  • A second Science paper from Naples Italy and Texas Children’s Hospital begins to look at pharmacological approaches to modulating the amount and location of TFEB. We know that adding lots of TFEB to JNCL and Huntington mouse models induces their cells to make more lysosomes. Now we also know that putting drugs called kinase inhibitors into dishes of cells stimulates normal existing TFEB sitting outside the cell to move into the nucleus and turn on all of those genes that make lots of lysosomes.76
  • Based upon data obtained in the CLN3 protein-deficient mouse, the University of Rochester initiates a clinical trial to test the safety and potential efficacy of short-term treatment with Mycophenolate mofetil (MMF), a potent immunosuppressive agent.81
  • In addition to trafficking inside the cell, engulfing material from outside the cell, programmed cell death, recycling and waste disposal, the loss of CLN3 protein results in motility defects in endothelial cells suggesting that CLN3 protein may play a role in wound healing outside and possibly inside the central nervous system. 25

2012

  • Investigators in Korea demonstrate that N-acetylcysteine (NAC), a well-known antioxidant, improves the health of cells from patients with Batten disease suggesting that NAC could benefit children with juvenile Batten disease.38
  • Investigators in the US demonstrate that mouse models of juvenile Batten disease benefit from AMPA-antagonists at various stages of development suggesting the presence of optimal treatment windows resulting from changes in disease pathology over time.40
  • US-based investigators provide preliminary evidence that suggests that boys with juvenile Batten disease develop symptoms earlier but girls experience a more aggressive disease including a shorter lifespan. 17

2013

  • Researchers in Korea demonstrate that white blood cells from juvenile Batten disease patients are different from white blood cells of children without Batten disease. Understanding what happens to different cells when they’re missing CLN3 protein will help us understand CLN3’s role in nerve cells (neurons) and how to fix it.34,35
  • Investigators working in Italy and the US test their hypothesis, that TFEB activation and clearance of accumulated waste material in a mouse model of lysosomal storage disease, improves cellular processing. Investigators are currently working on determining whether the same is true for juvenile Batten disease mouse models and patient cells.79
  • Building upon previous studies in the US, investigators in Denmark confirm that girls develop symptoms later than boys yet experience more aggressive disease. These studies are the first step to determining which hormones or other gender-specific factors accelerate disease and why. This information may be used to modify seizure or disease-modifying medications under development.62
  • Researchers in Great Britain explore the experiences of siblings of children with Batten disease to identify interventions that support their emotional health and family unit.52
  • Investigators in the US show that CLN3 protein, normally found in multiple locations in the cell but deficient or missing entirely in JNCL, changes its location in response to cellular stress. Understanding where proteins are found under various conditions helps investigators determine their functions.26
  • Evidence suggests that abnormal levels of calcium contribute to the death of nerve cells (neurons) in juvenile Batten disease. Researchers demonstrate that manipulation of calcium levels in cell culture models of Batten, prevents those cells from dying suggesting calcium regulation as a potential drug target in Batten.87
  • Researchers in France contribute to our understanding that different mutations in the juvenile Batten disease (CLN3) gene can result in profound differences in disease progression.65
  • Researchers in the US confirm that microglia, immune cells of the brain, are activated prior to signs of nerve cell (neuron) degeneration and provide further evidence that factors involved in microglial activation, Caspase-1 and hemichannel inhibition, may act as novel drug targets.91
  • Mouse models of juvenile Batten disease represent a powerful resource for investigating underlying disease mechanisms. Investigators in London provide new perspectives perspectives on how the central nervous system is affected, which may have implications in determining the efficacy of emerging therapeutics.43
  • Researchers in Spain compare protein degradation mechanisms in CLN2 versus CLN3 disease patient skin cells (fibroblasts). Whereas TPP1 activity is completely abrogated in CLN2 disease, TPP1 is only partially diminished in CLN3 disease. Overlapping deficiencies in TPP1 activity support the conclusion CLN2 and CLN3 are both part of the same lysosome-endosome pathway.86
  • Researchers in Finland employed Tandem Affinity Purification coupled with Mass Spectrometry with Significance Analysis of Interactome to identify potential interaction partners for CLN3 protein. Bioinformatic analysis revealed 58 potential binding partners, 16 of which were high confidence previously identified through other means.5 The identity of CLN3 binding partners supports the conclusion that CLN3 protein plays a role in transmembranre transport, lipid homeostasis, neuron excitability, G-protein signaling, and protein folding/sorting in the endoplasmic reticulum.74
  • It has long been a matter of debate whether children with the common deletion in their CLN3 gene, produce biologically active mutant protein. Researchers at Sanford Children’s Health Research Center in South Dakota show a substantial decrease in the transcript level of truncated CLN3 protein in patient fibroblasts and an analysis of expressed Cln3Dex1-6 mouse transcripts supports the conclusion that nonsense-mediated decay ensures that no protein is made.12,55 This contradicts earlier findings from Massachusetts General Hospital of Cln3Dex7/8 knock-in mice to reveal decreased yet stable mutant RNA levels consistent with CLN3 mRNA expression from patient tissue.20,31 In line with Massachusetts investigators in contradiction to those in South Dakota, investigators at University College London support the presence of mutant CLN3 transcripts and postulate the presence of CLN3 protein activity comparing healthy, and affected patient fibroblasts in the presence of RNA interference.39
  • The hippocampus, a small organ located inside the brain responsible for balance, emotions, short-term and long term memory, has been shown to undergo accelerated cell death in Alzheimer’s diseases as well as other forms of neurodegeneration. To assess whether the same is true in JNCL, researchers in Finland conducted a 5-year study on hippocampal volumes using magnetic resonance imaging. The mean total hippocampal volume decreased by 3.3% annually, which is higher than previously published reports and slightly higher than whole brain volume decrease of 2.9% per year. These results suggest that the absence of CLN3 protein may have region-specific effects on the brain which may be important for identifying biomarkers, treating symptoms and the function of CLN3 protein itself.82

2014

  • Investigators at Weill Cornell Medical Center developed an adeno-associated virus vector expressing the human CLN3 protein to reverse the CLN3 disease lysosomal storage defect, gliosis, and neuron loss. After 18 months, CLN3 transgene expression was detected throughout the brain, particularly in the hippocampus and deep anterior cortical regions. AAVrh.10hCLN3 administration resulted in significant reductions in storage material burden, a significant decrease in gliosis and a trend toward improved neuron counts. These data suggest CLN3 gene therapy will result in partial correction of CLN3 disease.78
  • Abnormal biometal metabolism is a feature of many neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease. Researchers in Australia show that biometal metabolism is dysfunctional in juvenile Batten (CLN3) mice and that biometal accumulation precedes significant neurodegeneration and parallels disease severity.28,36
  • CLN3 protein has long been proposed as an anti-apoptotic or agent responsible for preventing regulated cell death in healthy cells and some cancers.68,69 In a report from Biomedicine and Pharmacotherapy, researchers show CLN3 protein is highly expressed in colorectal cancer and that inhibition of CLN3 protein expression in these cells inhibits their expansion and promotes cell death. Understanding how CLN3 protein functions in multiple situations, both artificial and out of the ordinary, provides important clues as to its function in Batten disease.92
  • When discussing Batten disease, researchers and others often focus on neurons, the most vulnerable cell type in Batten. However, CLN3 protein is deficient in astroglia as well and considering the intimate interplay between astroglia and neurons, maintaining a healthy balance of neurotransmitters, researchers in Omaha and Japan examined the role of CLN3 in glia. Their findings show that CLN3-specific alterations in astroglia communication may impact the progression of Batten disease.7
  • By harnessing the power of technology for which the 2012 Nobel Prize in Physiology or Medicine was awarded, researchers at Massachusetts General Hospital and Harvard University, successfully reprogrammed skin cells (fibroblasts) from patients with juvenile Batten disease into induced pluripotent stem cells (iPSCs). IPSCs are produced by artificially “turning back the clock” of skin cells to a time when they were stem cell-like and capable of becoming any cell in the body. With a pharmaceutical nudge, these cells can then be pushed to become, not the skin cells they once were, but brain cells. In other words, successful reprogramming gives researchers their first opportunity to watch Batten disease develop directly in brain cells. Prior to this, efforts to study Batten disease were restricted to rodent models or human skin cells; neither of which accurately represents disease in the brain leaving without the proper tools to study the disease or a solid platform for testing drugs that will prevent, halt, or reverse its progression.47
  • The normal function of CLN3 protein remains unclear. CLN3 may be responsible for one function across many cell types, serve different functions inside a cell or both. To examine the function of CLN3 protein in endoplasmic reticulum (ER), researchers measured proliferation and cell death in cells treated with tunicamycin. Tunicamycin has been shown to promote cell death by causing the accumulation of misfolded or unfolded proteins in the ER. Their results demonstrating that normal CLN3 protein protects cells from ER stress-inducing tunicamycin, overexpression of CLN3 protein has an additive effect, and silencing of CLN3 leads to cell death supports the conclusion that CLN3 protein has a functional role in folding and processing proteins through the ER.90
  • Cdc42 protein is a small GTPase which regulates signaling pathways that control diverse cellular functions including scaffolding, intracellular trafficking, and endocytosis through actin polymerization/depolymerization. Because cell lines derived from patients and mice with CLN3 deficiency have impairments in these and other processes, investigators in Iowa hypothesized that CLN3 protein functions as a regulator of Cdc42 While they were not able to demonstrate a direct connection or functional role for CLN3, researchers demonstrate that active Cdc42 (Cdc42-GTP) is elevated in endothelial cells from CLN3 deficient mouse brain, and correlates with enhanced PAK-1 phosphorylation, LIMK membrane recruitment, and altered actin-driven events. They also demonstrate dramatically reduced plasma membrane recruitment of the Cdc42 GTPase activating protein, ARHGAP21. In line with this, GTP-loaded ARF1, an effector of ARHGAP21 recruitment, is depressed. Together these data implicate misregulated ARF1-Cdc42 signaling as a central defect in JNCL cells, which in-turn impairs various cell functions.73
  • Biomarkers, measurable characteristics of one’s health, disease severity or response to treatment, are critically important for the successful completion of a clinical trial. Without tools to measure its effect, there is no way of knowing whether a drug is beneficial, how beneficial ,or even whether it is harmful to patients. Researchers in Germany used spectral domain optical coherence tomography (OCT) to reveal increased accumulation of autoflourescent storage material and reduced thickness of the inner retina in 16-month old CLN3-/- mice. These results demonstrate the feasibility of OCT to assess neurodegenerative disease severity in an animal model of the disease which may have an important role in establishing efficacy or lack thereof in emerging clinical trials.27
  • Atomic structures of membrane proteins are playing a major role in understanding their individual functions and roles within cell systems. While several inferences have been made as to the 3-dimensional structure of CLN3 protein and many of these structures overlap or complement one another, the structure of CLN3 protein has not been experimentally proven. Researchers in Germany applied a combination of advanced molecular cloning, spectroscopy, and in silico computation to create a six-transmembrane domain and cytosolic N- and C-terminal model. This model largely agrees with often cited prediction models but differs with respect to the positions of the transmembrane domains and size of the luminal loops.70
  • Although gene defects most of the 13 forms of Batten disease are well-known, very little is known about how defects in these genes affect development and contribute to pathogenesis of disease.Investigators in California examined the timing of the expression of CLN2, CLN3 and CLN5 to determine that these three genes are co-expressed spatially and temporally during brain development suggesting that these three genes may play important roles during embryonal development alone or in concert with one another.21

2015

  • Researchers in the UK found that lack of functional CLN3 protein results in accumulation of waste material in the Retinal Pigment Epithelium (RPE) cells, cells that are vital for maintaining good retinal function. Targeting the RPE cells with therapeutic approaches could help slow vision problems in patients or even help restore vision.88
  • US researchers further studied the part of the brain that is responsible for motor coordination in a mouse model of juvenile Batten disease and find that AMPA receptor activity is enhanced, likely contributing to motor coordination problems. Their studies show that decreasing the receptor activity with an inhibitor results in immediate improvement of motor skill in young mice. These finds show that the CLN3 protein somehow interacts with the AMPA receptor and helps maintain normal AMPA receptor activity.40
  • US researchers do a comparative study of two mouse models of juvenile Batten disease in order to help researchers better select the most suitable mouse model for their studies and therapeutic testing.41
  • Researchers in China show that the CLN3 protein plays a role in ovarian cancer and may contribute to keeping cancer cells alive, growing and resistant to chemotherapy. This makes CLN3 an interesting target for cancer therapies but also helps Batten Disease researchers understand the different roles that the CLN3 protein plays in a cell.53
  • Researchers from Lebanon together with US and UK researchers, show that the CLN3 protein has increased expression in certain types of breast cancer and can contribute to cancer growth via interactions with other proteins, including ceramide. Not only does this make the CLN3 protein a potential biomarker as well as therapeutic target for cancer cells, this also helps Batten Disease researchers better understand CLN3 protein function in a cell.51
  • Researchers from Boston together with experts in the UK, create a new genetically accurate mouse cerebral cell line with fluorescent properties to better screen and identify new therapeutic targets for juvenile Batten Disease. Furthermore, through an initial screen done with molecules known to modify autophagy, researchers identified that the CLN3 protein is likely to play a role maintaining the cell’s calcium homeostasis, making the calcium pathway of the cell a new potential drug target for therapies.14

 

As you can see, even though Juvenile Batten disease has been known to exist for over 100 years, most of the research progress has been made in the last few years. For many families across America and around the world, this is quite literally a race against time. Science provides hope for a cure, but in order to turn this hope into reality, we need to raise enough capital to fund multi-year research programs, drug discovery projects, and clinical trials.

 

Because Juvenile Batten disease is so rare, affecting several hundred children in the United States, research aimed at finding a cure is also extremely underfunded. Of the $31.3 billion awarded by the U.S. Department of Health and Human Services for medical research in 2016, $1,670,876 million went to financing research for Juvenile Batten disease (1.2 per 100,000).89. Other rare diseases such as childhood leukemia which is 8 times more prevalent (4.5 per 100,000) received 100 times more ($167 million). 60,84 Almost two million dollars or six studies is not nearly enough to win the fight against a disease that, despite its obscurity, is the most common form of neurodegeneration in childhood.

 

While these various avenues of clinical research reflect the progress in our search for a treatment for NCLs, increasingly vulnerable funding sources threaten the ability of these scientists to continue their pursuit for a cure. The best hope we have for a treatment is in empowering investigators to continue their research into the mechanisms of NCLs to identify targets for therapies, work with the pharmaceutical industry to create drugs that match those targets and together, move potential treatments through clinical trials delivering them to children and families suffering from these devastating diseases.