NCL Research Newsletter April 2015

NCL Research Newsletter October 2014



NCL Research Newsletter April 2015


Main topic(s)

Scientific and medical meetings

Grants & Awards

Medical news & recent publications

New online resources


Main topic(s)


Towards hypothesis-driven therapeutic approaches for CLN3 disease (JNCL) (by Dr. Herman van der Putten)

               Kindly provided by the Beyond Batten Disease Foundation

Many activities highlight that the field of lysosomal biology and diseases is undergoing a true renaissance ever since Dr. Christian de Duve first described the existence of this organelle.. The lysosome has long lost its humble reputation as the cell’s trashcan and recycle center. It has moved into a front row position of the cell’s universe because of its central role in nutrient sensing and the regulation of cell growth and metabolism. The view that the lysosome acts in isolation has also been overhauled. Lysosomal function including the expression of lysosomal genes, lysosomal biogenesis, autophagosome number and fusion with lysosomes and lysosomal exocytosis, altogether promoting cellular clearance, is subject to global transcriptional regulation by TFEB. Furthermore, the list is growing of inter-organelle contact sites, also serving critical roles in lysosome homeostasis. Besides those within the endo- and autophagosomal lysosomal network, others include lysosome-endoplasmic reticulum (ER), lysosome-mitochondria and, as shown most recently, lysosome-peroxisome membrane contact sites playing a role in the transport of cholesterol from lysosomes to the plasma membrane. Therefore, it is no surprise that lysosomal storage diseases including some of the NCLs are caused by defects in genes encoding proteins acting upstream or downstream of the lysosome. For example, CLN6 and CLN8 seem confined mainly to the ER while the CLN3 protein, defective in JNCL, seems localized predominantly in late endosomal and lysosomal compartments. In brief, scientific and technological developments in the rapidly moving field of lysosome biology are opening avenues both for new therapies as well as for refining and improving existing therapeutic approaches.               
To facilitate and accelerate testing of much-needed treatments for JNCL, it is critical to understand and bridge research gaps and remove obstacles on the route to translating findings to the clinic. It is important to gather clinical information that informs on primary and secondary outcomes in patients and outcomes that can realistically be targeted in clinical trials. For this reason natural history data for JNCL continue to be collected that include both static as well as age-related data relevant to disease progression and specific clinical phenotypes such as seizures (Pubmed abstract 1, abstract 2, abstract 3, abstract 4, abstract 5)


This information will hopefully provide the essential information needed to successfully move therapies to the clinic. Ideally, clinical observations and CLN3 data gathered in research laboratories should help guide and define hypothesis-driven clinical endpoints and facilitate exploring and testing novel therapeutic avenues discussed in recent meetings and publications.



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Scientific and medical meetings 


Several exciting meetings took place recently where researchers, clinicians, representatives from pharma, biotec, and family groups met to report and discuss progress in the biology and therapy of NCLs and other lysosomal storage diseases. The NCLs were the focus of the 14th International Congress on Neuronal Ceroid Lipofuscinoses in Cordoba, Argentina, October 2014 (soon there will be a special BBA issue; a summary of this meeting is also available upon request by Email).
In November 2014, the Beyond Batten Disease Foundation (BBDF) and the New York Academy of Sciences organized a unique think-tank workshop to discuss drug-targeting the lysosome. This meeting involved top experts from different disease areas including neurodegeneration and cancer. The main goal of this workshop was to pool resources and brainpower, and work together to identify therapeutic strategies to manipulate the lysosome to the benefit of many patients, including those suffering from CLN3 disease (JNCL). Prior to the meeting, all participants attended excellent webinars that are available on the BBDF website and that served as a solid knowledge foundation for discussions during the workshop. 


In December 2014, the NCL Foundation organized its 12th national NCL congress in Hamburg that included clinical experts, researchers from academia and biotec in and outside the NCL field, and representatives from nonprofit organizations including the BBDF (USA), the BDSRA (USA), the BDFA (UK) and BRF and BB (NL). This meeting was focused on iPSC-derived cellular systems as translational models for NCL. Dr. Angela Schulz (Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg) gave a very clear and concise introduction on the clinical course of JNCL to the participants, several of which were new to NCL research. Dr. Susan Cotman (Center for Human Genetic Research, Massachusetts General Hospital, Boston) discussed human iPSC-based CLN3 models and their application in therapeutic discovery and described in two recent papers (Pubmed abstract 1, abstract 2).


                  Frank Husemann (founder of the NCL Foundation); 12th national NCL 

                  congress in Hamburg


Dr. Stephen Chang (The New York Stem Cell Foundation, New York) gave an update on novel human CLN3 iPSC lines generated in collaboration with the Beyond Batten Disease Foundation. Dr. Marco Sardiello (Texas Children’s Hospital, Houston), who received the 5th NCL Research Award, discussed leveraging TFEB activation of lysosomal clearance to develop therapeutic strategies for JNCL. Other topics covered included iPSC-based retinal cell and organoid models, iPSC-derived neuronal, cortical network and glial models, the derivation and expansion of human neural progenitors and chemical approaches to control stem cell fate, as well as assays for finding and validating therapeutic approaches in iPSC-based systems. In summary, human iPSC-based models seem to hold great promise to facilitate target discovery and target validation for JNCL and work in several laboratories is ongoing to try and achieve this goal.


In February 2015, the Brains for Brain (B4B) Foundation led by Dr. Maurizio Scarpa and Dr. David Begley, organized its 9th European Workshop in Frankfurt to discuss recent advances in research and clinical achievements in the field of neurodegenerative lysosomal storage disorders and how to bridge the blood brain barrier to achieve therapeutic effects in the central nervous system. Next year, the B4B Foundation will celebrate its 10th anniversary and the meeting is scheduled for March 14-19 2016.

In March 2015, a Gordon Research Conference (Galveston, Texas) focused on lysosomal storage diseases. The main theme was defining pathogenesis and therapeutic strategies for lysosomal diseases.

Another GRC, relevant to lysosomal biology and disease will take place in June in Waltham, Massachusetts. This GRC is co-chaired and co-organized by Dr. Haoxing Xu (University of Michigan) and is focused on organellar channels. In the endo-lysosomal system, channels play a critical role in maintaining organellar homeostasis.


Interview with Haoxing Xu, Ph. D., Associate Professor Department of MCDB


Dr. Xu, what is your (current) research focus and why did you chose this one?

“We are currently working on ion channels and Ca2+ signaling in the lysosome. A particular focus is TRPML1, a protein that is not functioning properly in Mucolipidosis type IV patients. We have recently developed a new and powerful electrophysiological method to directly study how TRPML1 functions in the lysosome. There are two main reasons that I chose to work on TRPML1 channels. First, I



      Haoxing Xu, Ph. D., Associate 

      Professor Department of MCDB, 

      University of Michigan


was trained as an electrophysiologist, and used to work on ion channels of the plasma membrane for more than 10 years before I started my independent position at the University of Michigan. Working on ion channels of intracellular organelles was a new challenge for me. Second, we recently found that manipulating the channel activity of TRPML1 can be a viable approach to treat neurodegenerative and muscle diseases”. 


What were the major advances in the last few years in regard to understanding the function of membrane proteins? What are the bottlenecks?:

“With the development of lysosome patch-clamp technique, we were able to understand the physiological functions of TRPML1 channels, as well as other lysosomal ion channels. In addition, recent technical advances in super-resolution microscopy, organelle-targeted fluorescence imaging, and organelle proteomics have pushed a large step forward in the research of intracellular ion transport. However, functions of many other lysosome membrane proteins are still unknown. More organelle-targeted fluorescence imaging methods need to be developed, e.g., lysosome-targeted membrane potential dyes or genetically-encoded sensors”.

We have heard that you are the organizer of a new Gordon Research Conference. Could you please tell us a little bit about it (main topic, areas which are going to be covered, can you still apply to participate…).:

“Yes, this Gordon Research Conference (GRC) on Organellar Channels and Transporters, with its inaugural meeting scheduled for June, 2015, is one of the newest of over 170 annual conferences organized by the GRC, an organization known world-wide because of the high-quality, cutting-edge nature of its conferences. This new GRC meeting will be dedicated to ion channels and transporters of intracellular organelles, including mitochondria, endosomes, lysosomes, vacuoles, the endoplasmic reticulum (ER), nucleus, and chloroplasts; in both animals and plants.  The meeting will bring together about 150 scientists of many types, with different technical expertise and scientific backgrounds.  Topics of the conference will be discussed in 8 separate platform sessions, and will include electrophysiology, molecular identification, proteomics, regulation, interaction partner, targeting, pharmacology, structure, and physiology.  A special session will focus on how dysfunctional ion/metabolite transport in organelles leads to common and rare human diseases, and how the activity of organellar channels can be manipulated to treat them.  The complete program will come at an exciting time within this field, and will welcome the expanding group of scientists who are becoming interested in intracellular channels and transporters as they relate to basic science and applied biology. Currently there are still opening spots.  In a few weeks after the closing of the registration deadline, we will select up 13 short talks and three late-breaking topics on organellar channels and transporters”.

What’s the overlap between your research and CLN3 research?:

“There are overlaps in several aspects.  First, the cellular phenotypes of ML-IV and CLN3 are rather similar.  Second, CLN3 pathogenesis may involve impaired lysosomal ion homeostasis and Ca2+ signaling.  Third, manipulating the channel activity of TRPML1 can be a viable approach to treat some LSDs, including CLN3 and other NCLs”.



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Grants & awards


Research prize won by an NCL-project, also funded by the NCL Foundation

The collaborative project “HUMAN RETINA JUVENILE CEROID LIPOFUSCINOSIS DISEASE MODELLING” of Dr. Mike O. Karl and Prof. Alexander Storch (both Dresden, Germany) was awarded 2nd place of the "EYEnovative Förderpreis“ of Novartis. Scientific projects as well as clinical studies in the area of ophthalmology are funded by this prize.   


   Microscope picture of 85 day old   

   JCNL retina organoid live in culture

   (courtesy of Cristina Golfieri)

In Jan 2015 the NCL Foundation started funding this project led by stem cell expert Prof. Storch and retina expert Dr. Karl. The retina is

part of the CNS and an extremely important topic for research and therapy in JNCL. JNCL is characterized by early-onset and rapidly progressing retinal degeneration. A variety of non-invasive techniques exist to monitor changes in retinal structure and function which, at least in early diagnosed patients, might help to track therapeutic effects of treatments. Postdoc NCL-fellow Cristina Golfieri is developing new human induced pluripotent stem cell-based JNCL ex vivo retinal cell and 3-dimensional organ models with the goal to better understand the disease process and develop human ex vivo cell and 3-dimensional organ models for testing new therapies.
Dr. Mike O. Karl (Groupleader at the DZNE and DFG-center for regenerative therapies Dresden): "JNCL is the most common cause for neurodegeneration in childhood. Especially the early loss of sight has a major impact on life quality for affected children and their families. Other brain areas are deteriorating at a later stage of disease progression. Our new model opens up new avenues to explore the pathogenic cascades as well as to develop new therapies.“



Childhood and adult dementia: Any overlaps?


The “Dorit & Alexander Otto Stiftung“ together with the NCL Foundation seed funded a new PhD position to decipher the relationship between NCL childhood dementia and adult Alzheimer dementia. The research group of PD Dr. Guido Hermey (Center for molecular neurobiology Hamburg) is investigating interactions between the CLN3 protein and a protein which function was discovered in the context of adult dementia. The PhD student Abuzar Kaleem will try to further verify, validate and understand the meaning and implications of this interaction for connections between an orphan disease and another more common form of adult dementia that many elderly suffer from.


PhD - Fellowship and "Kindness for Kids Versorgungspreis"

Kindness for Kids announces a PhD fellowship to contribute to therapy development for rare pediatric diseases. The Health Care Award Kindness for Kids is endowed with a maximal amount of 40 000 Euro and funds the implementation of a project that aims to directly improve situation of children living with a rare disease through structural changes or with a new therapeutic approach.

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Medical news & recent publications



New findings about the TPP1 enzyme replacement therapy in a canine model have been published. Neuropathological evaluation demonstrated the clearance of lysosomal storage, preservation of neuronal morphology, and reduction in brain inflammation with treatment.
Repeated intracerebroventricular infusions of the enzyme delayed the onset of neurologic deficits, improved performance on a cognitive function test, reduced brain atrophy, and increased life span. Pubmed abstract 1, pubmed abstract 2


The timing of expression of CLN2, CLN3 and CLN5 genes was investigated in developing mouse brain. It seems like these genes are co-expressed spatially and temporally during brain development in the neural progenitor cells together with known stem cell markers. Pubmed abstract


There is a new experimental CLN3 model organism - social amoeba Dictyostelium discoideum. Pubmed abstract


Seizures in JNCL are most commonly generalized tonic-clonic, though infrequent. The Batten study group just published new data showing that myoclonic seizures are infrequent. Pubmed abstract


New CLN5-mutations have been found which cause an adult-onset autosomal recessive ataxia. Pubmed abstract


Compound heterozygous variants in MFSD8, a gene encoding a lysosomal transmembrane protein, were identified in 2 families with macular dystrophy and showing a normal ERG but a reduced mfERG. These findings highlight, that depending on the type of mutation phenotypes may range from syndromic to non-syndromic and involving perhaps only a single organ such as the retina. Non-syndomic mutations have also been discovered in CLN3. Pubmed abstract


A new CLN11 mouse model has been established. Accumulation of autofluorescent material was present in these Progranulin deficient mice at 12 months. Degeneration of multiple classes of neurons including photoreceptors and retinal ganglion cells was noted in mice at 12 and 18 months. Pubmed abstract



Latest progress and outlook


Rapid progress is seen in enzyme replacement therapy (ERT) for CLN2 (clinical Identifier: NCT01161576), and for gene therapy (GT) in CLN1and CLN2 (clinical Identifier: NCT01907087). Preclinical results in CLN5-deficient sheep suggest, that also CLN5 deficiency may be therapeutically targeted using GT. CLN3 disease and some of the other NCLs, present a more complex therapeutic problem. “Soluble” proteins (such as encoded by CLN1, CLN2 and CLN5) are subject to a phenomenon referred to as cross-correction (i.e. cells that themselves were not targeted by therapy can take up these proteins that are produced and secreted by cells that were targeted. This can result in restoring function even in non-targeted cells). It is much harder to imagine how this can be achieved for transmembrane proteins, although perhaps not impossible if organelles could also move from cell-to-cell. Gene therapy for TM proteins including CLN3 has only met with partial success. On the other hand, significant progress is being made in understanding CLN3 function. For example, a very recent report by Susan Cotman and collaborators shows that the CLN3 protein has an important role in intracellular Ca2+ handling and in autophagic pathway flux. These authors also established a new screening platform for drug discovery. Another very interesting approach was presented at the NCL conference in Cordoba by Dr. Michelle L. Hastings in collaboration with Isis Pharmaceuticals. These investigators have developed antisense oligonucleotides that target CLN3 splicing and can restore the reading frame that is lost in most cases of CLN3 disease because of a deletion of exons 7 and 8. Also, a new preclinical CLN3 minipig model is being developed that may help to better understand the disease and facilitate the development of therapies. As more and more of missing pieces of the CLN3 puzzle are being revealed, hope rises that some will translate into hypothesis-driven therapeutic approaches that can be tested in patients.



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New online resources


Medical education movie
The NCL Foundation has developed a medical education movie addressing ophthalmologists and pediatricians. This movie was also supported by Batten Research Funds.

Online webinar tutorial
Beyond Batten Disease Foundation and partners created ADDF ACCESS, which is a curated database of contract research organizations (CROs) with specialized expertise in drug discovery for neurodegenerative diseases. This resource will provide users with strategic guidelines on when to outsource, how to evaluate CROs, how to manage relationships with companies, identify CROs specializing in brain diseases, and streamline bid collection from multiple CROs for your institution or grant.

There will be an online webinar tutorial to view a live demonstration on how to identify CROs and consultants, communicate directly with vendors, compare proposals tailored to your unique requirements, and find educational resources on drug discovery and development.

When: Monday May 18, 2015 or Tuesday May 19, 2015
Time: 11:00 AM EST / 10:00 AM CST
Dial-in number: 877-610-0152
Conference code: 6207705763
Click for screen-share:

For more details or assistance contact:
Danielle M Kerkovich, PhD
Principal Scientist | Beyond Batten Disease Foundation


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NCL Research Newsletter October 2014


Main topic(s)

Medical news & recent publications

Scientific and medical meetings

Grants & awards

Job offers


Main topic(s)


CLN3 – One gene, multiple clinical manifestations (by Dr. Herman van der Putten)

Dr. Herman van der Putten,
Head of Research at NCL Foundation

Two recent studies suggest that mutations in the Batten disease gene CLN3 are associated with a broad spectrum of clinical phenotypes. Mutations in CLN3 are known to cause the juvenile form of neuronal ceroid lipofuscinosis (JNCL) or Batten disease. In JNCL, first symptoms are usually loss of vision between age 5 and 10, followed by mental decline, motor coordination deficits, seizures and frequently cardiac problems. Some CLN3 mutations appear to cause a more protracted course of the disease. Now, one study reported that CLN3 mutations can cause Retinitis pigmentosa (RP) without any signs of Batten disease. The patients in this study were in their 40s, 50s and 60s. Yet another novel mutation was found in two brothers that presented with visual failure, seizures, and prominent cardiac involvement, but only mild cognitive impairment and no motor deterioration after 40 years of disease. The multiorgan syndrome in these two patients also included autophagic vacuolar myopathy (AVM). AVMs are a heterogeneous group of disorders characterized by vacuolation of skeletal muscle, cardiomyopathy, myopathy, mental retardation and variable retinopathy. Mutations in genes causing AVMs include VMA21 and LAMP2. VMA21 mutations prevent vacuolar ATPase (V-ATPase) assembly whereas LAMP2 plays roles in lysosome/autophagosome fusion and chaperone mediated autophagy.  It remains poorly understood why dysfunction of CLN3 and other widely expressed lysosomal membrane proteins, which act at crucial steps of the lysosomal life cycle, affect specific cell-types. One possibility is that different CLN3 mutations affect cellular processes and compartments to different degrees. Regardless which CLN3 mutation, the retina is always affected which suggests, that one or more retinal cell types highly depend on wildtype CLN3 function. Right now, a molecular explanation for the different CLN3 genotype-phenotype associations remains enigmatic. The function of wildtype CLN3 is poorly understood. CLN3 deficiency can cause an accumulation of the cation-independent mannose 6-phosphate transporter in the trans-Golgi network, and this could lead to trafficking defects of newly synthesized digestive enzymes to the lysosome. Perhaps, different CLN3 mutations impact this process to variable degrees. A more in depth understanding of CLN3 function is needed to answer these questions.


To accelerate research we need to think outside the box. What is the link to other diseases? Which scientific expertise is missing? More research gaps will be addressed during the roundtable discussion on the last day of the 14th International NCL Conference (Sunday, 26th of October, 2014, 8:30-10:00).


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Interview with Inés Noher de Halac, the organizer of the 14th International NCL Conference in Argentina


Inés Noher de Halac, organizer of the 14th International NCL Conference in Argentina

We would like to introduce to you the organizer of the 14th International Conference on Neuronal Ceroid Lipofuscinoses, in Córdoba, Argentina, Inés Noher de Halac. Every two years scientists from all over the world working on Batten Disease get together, develop ideas and discuss latest findings.


Inés, why did you become a biologist and what were your goals at the beginning of your studies?

Inés Noher de Halac: I wanted to study medicine all my childhood, but as my father died when I was 16, I became afraid to have an activity so near to human suffering. So, I studied biological sciences. My goals at the beginning of my studies were to learn more about the secrets of life. Besides that, I was interested in science, but not too much in mathematics.

NCL is a very rare disease. Was there a special occasion why you have specialized in this particular research area?

Inés Noher de Halac: I admired very much the pioneer work of my teacher Dr. Raquel Dodelson de Kremer in Argentina who introduced me to the world of these “not so rare” diseases. In 1993 she needed a researcher in the field of electron microscopy. She asked me to join her team as I was specialized in that technology. So I began to recognize the peculiarities of the NCL bodies in human cells. I joined with enthusiasm the challenges of her research team. Later on we organized a research group specialized on NCL research that I was leading.

What are your experiences how Argentina deals with rare diseases?

Inés Noher de Halac: Only in recent times our health authorities became interested in rare diseases. Since July 2011 we have a national law of “less frequent diseases” approved by our parliament. Since then some progress has been achieved. Families with affected members now have more rights to get care from the state, but it is still a long way for obtaining what we need.

What can you tell us about the current medical care in Argentina?

Inés Noher de Halac: There are immense inequities to overcome. Needs are much bigger than achievements. In the few referential centers for that kind of diseases researchers and professionals are dedicated and have in general good knowledge and skills, but human resources are scarce, because the salaries are frequently too low and good positions not available. The money the government puts in medical care might be enough, but corruption is high.

What exactly was your motivation to organize the International Conference on Neuronal Ceroid Lipofuscinosis (Batten Disease) in South America?

Inés Noher de Halac: Our colleagues around the world encouraged us to take this responsibility. We were so happy that they believed in us, and we were convinced that the NCL community could have a good experience in Argentina. The Congress is organized alternatively in one and the other side of the Atlantic Ocean, but America is not only North America, South America is an important part of the continent. We wanted to disseminate the discussion on this kind of diseases from a scientific perspective in South America. To host the congress in Argentina opens the door for more research and for the first time calls attention to these pathologies on an international level in South America. 

Can you give us a brief insight into the priorities of this year´s International NCL Conference?

Inés Noher de Halac: The strongest fields will be genetics, cell biology, new experimental systems and other basic science approaches oriented towards new therapeutic perspectives. Another question that emerged is the translational medicine “from bed to bench” with a perspective on “rare disease” for the NCL research. A valuation of the phenotypes is visible, and not only the genetic variants of disease. The approaches are no more sorted by NCL types, but centered in genomics, proteomics, cell biology and basic pathogenic phenomena. The discussion “What is NCL?” is intended to re-elaborate old conceptions in the genomics era. Links to other diseases are gradually emerging. Some bioethical definitions are discussed for the first time in an international NCL conference, as well as the priority of international cooperation in the field of orphan drugs and disease. An outstanding issue in the conference is the translation of research progress into information to the international patient’s organization meeting. This will be achieved by means of the “Marketplace” and the final round table.

To conclude, it would be great if you could give us a few suggestions how to prepare for Argentina, for those who have never been there.

Inés Noher de Halac: I would suggest a website that has recommendations for people travelling to Argentina: It will be a unique possibility for you to explore Argentina´s culture. Food is very good and people are usually friendly. Take care of yourself just as you usually do when travelling to other countries. Be careful with your big cameras and sophisticated equipment in the streets. I am sure your experience will be unforgettable and you will have a lot to tell your families.

We look forward to welcoming all the international visitors in Cordoba City!


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Medical news & recent publications


Novel insights from studies using human iPSC-based cellular systems

(by Dr. Herman van der Putten)

Human skin fibroblast-derived pluripotent stem cells (iPSC) are becoming mainstay to model cell-autonomous as well as cell non-autonomous disease phenotypes in a dish. These human cellular systems are starting to impact drug discovery, in the hope they will facilitate translation to the clinic. A wide variety of disease-relevant human cell types including motor and dopaminergic neurons, cardiomyocytes and retinal pigment epithelial cells have successfully been generated from iPSCs. In a number of cases, disease phenotypes have been obtained and shown to be reversed using pharmacological treatments. In a proof-of-concept study, Susan Cotman (Boston, USA) together with colleagues in Dresden and Münster (Germany) have shown, that CLN3 iPSCs have abnormal endosomal/lysosomal structures and that CLN3 iPSC-derived neural precursors and mature neurons display abnormalities in organelle structure and the accumulation of lysosomal storage material. These extremely encouraging results suggest that CLN3 disease-related cellular phenotypes are partially mimicked in the culture dish. Rapid progress is also being made in generating human iPSC-derived “organs in a dish”. These 3-dimensional tissues offer the possibility to study cell-type specific effects of mutations in a complex tissue environment. Rescuing the degenerating retina in Batten disease is a major challenge and recent success in generating iPSC-derived neuroretinal cell types and retina-like structures (publications 1, 2 and 3) holds great promise to model human CLN3-associated retinal phenotypes and test treatments. Findings in such retinal models may also translate to central neurons since the retina is an extension of the brain. Altogether, CLN3 iPSC-derived cellular models might open the door to identify treatments that can alleviate CLN3-dysfunction and help design readouts for proof-of-concept trials in the clinic.


Experts working on the differentiation of iPSCs to retinal cells, neuronal cells and cardiomyocytes will be presenting their findings and ideas during the 12th National NCL Congress in Hamburg, Germany (Dec 15, 2014).


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Batten disease publications 2014 (extract)


A combination of 2 drugs is being tested in patients suffering from infantile NCL. Pubmed abstract



Currently CLN2-patients are being treated with a TPP1-enzyme replacement therapy in a clinical study. Study centers are in Hamburg (Germany), London (UK) and Rome (Italy). Recently first results obtained in a canine model have been published. Pubmed abstract 1, Pubmed abstract 2


A JNCL patient was treated with immunosuppressive therapy. Visual function has been characterized.
Pubmed abstract


The ARF1-Cdc42 pathway might be a target for JNCL therapy developmen. Pubmed abstract


Altered biometal homeostasis is a key feature of CLN1, CLN3, CLN5 and CLN. Pubmed abstract


Cysteine String Protein alpha oligomerizes in adult NCL mutants
Pubmed abstract 


A new mouse model is available recapulating most of the neuropathological features of human CLN7 disease.
Pubmed abstract

There is an overlap between NCL and Parkinson’s disease.
Pubmed abstract 1 , Pubmed abstract 2

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Scientific and medical meetings



22-26 October: 14th International Congress on Neuronal Ceroid Lipofuscinoses (Batten Disease), Córdoba, Argentina. Every two years scientists working on Batten Disease meet and discuss new findings. This conference is usually aligned with an international family meeting.

19-21 November: The workshop “Drug Targeting the Lysosome” will take plac
e in the New York Academy of Sciences’ conference center in New York City. For more information, please get in touch with the Beyond Batten Disease Foundation

15 December: 12th National NCL congress (Hamburg, Germany) will cover the topic “iPSC-derived cellular systems as translational models for NCL”.



5-7 February: Scientists working on the blood-brain-barrier will meet researchers of the lysosomal storage disease field. 9th Brains4brain Workshop in Frankfurt, Germany. If you want to participate, please get in touch with Prof. Mauricio Scarpa and/or Prof. David Begley.


9-13 February: The 11th Annual WORLDSymposium™ will take place in Orlando, USA focusing on lysosomal storage disorders.


27-28 February: During the 2nd Heidelberg Symposium of the pediatric center Dr. Angela Schulz will give insights into the current CLN2 ERT tria.


15-20 March: Lysosomal disease will be covered in depth during the Gordon Conference in Galveston, USA.


23-26 April: 41st annual meeting of the Society of Neuropediatrics in Basel, Switzerland.


14-19 June: A new Gordon Conference will cover “Organellar Channels & Transporters” in Waltham, USA.


1-3 July: 3rd Rare Diseases Summer School in Wädenswil, Switzerland.


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Grants & awards


NCL Foundation awards research team of Dr. Marco Sardiello, Baylor College of Medicine, Houston, with 5th NCL Research Award


Dr. Marco Sardiello

The NCL Foundation is delighted to announce that the 5th NCL Research Award goes to Dr. Marco Sardiello and his team at Baylor College of Medicine, in Houston, Texas. The official hand-over of the award will be later this year. The award, which amounts to € 100,000, is to finance a postdoctoral fellow who’s work will be dedicated to unraveling the primary role of the wildtype CLN3 protein and the lysosomal defects that result in Batten disease where both copies of the CLN3 gene are mutated. Dr. Marco Sardiello and his team hope to gain insight into roles of CLN3 that can be translated to the clinic and that can pave the road to therapy. The funds for the NCL Research Award came from the proceeds of charity dinners and an art auction organised by the NCL Foundation.

Dr. Marco Sardiello and his team are dedicated to the research and development of innovative therapies to treat lysosomal storage diseases (LSDs). LSDs are the most common neurodegenerative diseases of childhood. The majority of LSDs are caused by defects in one of over 60 known soluble lysosomal enzymes. Lysosomes are cellular organelles that play a key role in the degradation and recycling of cellular organelles, proteins, lipids and other substances. Therefore, defects in genes that encode lysosomal enzymes or proteins whose function is essential to maintain lysosomal homeostasis, have devastating effects in cells and organisms. The latter, because of an excessive accumulation of waste and toxic substances inside cells, often resulting in cell death. Transport mechanisms exist that allow soluble enzymes to travel from one cell to another. Hence, candidate therapies for enzyme deficiencies include enzyme replacement therapy, bone marrow transplantation, or gene therapy. The wildtype CLN3 gene, however, encodes a transmembrane protein which in Batten disease/JNCL is defective and many neurons die. For this reason candidate therapies targeting soluble enzyme deficiencies are generally not considered for treating JNCL. However, Marco Sardiello’s laboratory leverages the idea that therapeutic approaches for JNCL perhaps can benefit from strategies that are currently exploited to treat “classical” LSDs.



BDSRA Announcement: On October 1, 2014

BDSRA has issued an open call for Letters of Intent (LOI) for grant projects related to Batten disease. The LOI should describe proposals of innovative research that have the potential to advance therapeutic strategies for all of the Neuronal Ceroid Lipofuscinoses. Each award, depending on funding availability, will be no more than $60,000 over a one-year period. Letters of intent must be submitted by November 15, 2014. The LOIs will be reviewed by members of the BDSRA board and invited scientific reviewers. Requests for full proposals that will be peer reviewed will be made in February, 2015. Awards will be announced midyear. For more information visit the BDSRA webpage.


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Job offers

Please inform us if you are looking for students (Bachelor, Master or PhD) as well as PostDocs in the field of NCL research. We can try to advertise it in our NCL Research Newsletter.