FEATURE ARTICLE: NCL 2023 Congress Research Report

International Congress on Neuronal Ceroid Lipofuscinoses, Hamburg, Germany | September 26-30, 2023

Last month, BDSRA Head of Research & Medical Affairs Dr. Ineka Whiteman attended NCL 2023 with President & CEO Amy Fenton Parker, in the beautiful city of Hamburg, Germany.

Attended by over 200 in-person delegates, this biennial meeting provides a forum for scientists, clinicians, and biotech industry partners to present and discuss the latest advances in basic science, translational, and clinical research across all forms of Batten disease. Below is a daily overview of the scientific program.

Day 1: A Global NCL Patient Group meeting was held, co-chaired by our own Dr. Whiteman and Dr. Frank Stehr from the NCL Stiftung, Germany. Eleven patient groups and six industry companies attended, with discussions focusing on potential collaborative initiatives. Biotech partners delivered clinical program updates and engaged in open dialogue with our patient groups.

Day 2: Basic Science Day: This day’s presentations detailed the latest discoveries in NCL biology, novel roles, and functions of various NCL-related genes and proteins. Researchers showcased cell and animal models of NCL, in addition to new biomarkers that serve as useful, objective indicators of disease progression.

Day 3: Translational Research Day: Presentations focused on therapeutic approaches to treat various forms of Batten disease, including small molecule, cell, and gene-based therapies.

Day 4: Clinical Research Day: Clinician investigators and biotech companies presented some of the latest results from new and ongoing in-human clinical studies. This is an exciting time for NCL therapeutic development, with seven studies currently active around the world, including treatments with gene therapy, small molecules, and repurposed drugs across four forms of Batten disease, and several others in the pipeline (a summary of all studies can be viewed by clicking here).

Dr. Whiteman presented research on the CLN3 disease timeline of symptom onset and progression, developed in collaboration with leading clinicians from the U.S., Germany, Denmark, and Australia. We will share more on this work in the near future.

Day 5: Family Day: This is an NCL congress tradition, where families are invited to attend a half-day session dedicated to them. Lay summaries from all the scientific and clinical talks from the week (there were over 60!) were presented to families, with time for questions and discussion. At lunchtime, a “Marketplace” was set up for families to visit booths with information about specific research projects, clinical trials, patient resources, advocacy groups, and more.

We would like to thank Co-Chairs Dr. Angela Schulz and Dr. Jonathan Cooper for their extraordinary work and efforts in bringing this event and scientific program together. Next up is NCL 2025, which we’re excited to share…. is heading down to Australia!

CLINICAL PROGRAM UPDATES

Clinical Trial Tracker

Have you seen our NEW chart tracking clinical trials for Batten disease? Learn more with this Toolbox Tuesday video. View the chart by clicking here.

Promising 12-month results in the Phase I/II trial of Batten 1

The Beyond Batten Disease Foundation (BBDF) and biopharmaceutical company Theranexus, have presented interim results for efficacy and safety after 12 months of treatment in their Phase I/II trial for CLN3 disease at the NCL 2023 Congress in Hamburg, Germany last month.

The new data further supports the 6-month treatment results announced in mid-June 2023, and show after 12 months of treatment:

  • An average 32% decline in neurofilament light chain (NfL) levels was observed in patient serum (a 17% reduction was observed after 6 months’ treatment). NfL is a recognized biomarker of neurodegeneration.
  • There was a 64% reduction in NfL observed in the cerebrospinal fluid (CSF); and
  • A reduction in glycosphingolipids (GSLs), including a 45% reduction in Gb3. (accumulation of GSLs is known to be toxic to neurons).

Clinically, there was notably less worsening of motor symptoms evaluated by the modified UBDRS physical assessment subscale after 12 months, compared to the expected progression observed in natural history cohorts.

To read more, please click here to read the official press release, published on September 29.

RESEARCH OPPORTUNITIES

SPEECH & LANGUAGE STUDY – CLN2 and CLN3 Batten disease

WE STILL NEED YOUR HELP!

Thank you to all those families who have already signed up and participated in the world-first research study into the characterization of speech and language in individuals with Batten disease (CLN2 and CLN3 disease).

To complete the project, the research team is seeking a few more participants and they would be grateful for your help.

Participation is open to individuals worldwide who are:
– Affected by CLN3 or CLN2 Batten disease
– Age 6 months and older
– Verbal or non-verbal

Bereaved caregivers are also invited to take part in this study.

To find out more about the project and how to get involved, download the flyer by clicking here or contact the team at Murdoch Children’s Research Institute, Melbourne Australia at geneticsofspeech@mcri.edu.au

USING AI TO IDENTIFY GENETIC CONDITIONS – Calling all NCL families

In one paragraph, how would you describe your child’s condition?

The National Human Genome Research Institute (NHGRI), part of the National Institutes of Health (NIH), develops and studies computer-based technologies to better understand medical conditions that have known or suspected genetic causes.

The team is currently studying how different artificial intelligence (AI) models, including public models like ChatGPT, can identify genetic conditions. These models are a growing part of healthcare, and this project seeks to compare how well different models work.

For this study, they are collecting short descriptions from people with genetic conditions (or their carers) so that these different models can be tested. Participants are asked to send one paragraph describing the condition (eg. Batten disease, and subtype) in their child. Please use whatever description is most natural for you. That is, use your own words in the way you might describe the condition to a clinician meeting you for the first time. All contributions will be de-identified.

A copy of the information leaflet can be downloaded here.

Please send descriptions to the NIH project team by emailing medicalgenomicsunit@nih.gov

For any inquiries, please feel free to reach out to the above email or contact Dr. Ineka Whiteman at research@bdsraaustralia.org.

FAMILY REGISTER 

Have you joined the Register yet?

The BDSRA Foundation Family Register is a vital tool that enables us to keep you informed of ongoing Batten disease research, including future clinical research opportunities.

The Register also enables the BDSRA Foundation to better understand the prevalence of Batten disease, including the different subtypes and geographical locations. This helps us tailor our education and support activities according to the needs of our families. The Register is open to all current and bereaved families.

The information collected in this form is kept STRICTLY CONFIDENTIAL. Your involvement in this survey is entirely voluntary, and you may request to be removed from the list at any time. The form takes just a few minutes to complete and can be accessed by clicking here.

Thank you for participating in this important initiative!

PUBLICATION SUMMARIES

Review: Treatment of non-epileptic episodes of anxious, fearful behavior in adolescent CLN3 disease

Recurrent non-epileptic episodes of frightened facial and body expression reportedly occur in more than half of post-adolescent patients with CLN3 disease. Clinically, the episodes look similar to the seizures normally seen following acute traumatic brain injury (TBI), known as paroxysmal sympathetic hyperactivity (PSH). This review by Prof. John Ostergaard at Aarhus University Hospital, Denmark, suggests episodes in patients with CLN3 disease are often triggered by separation (e.g., from the primary carer), loud sounds, or the exposure to “uncomfortable stimuli” such as lifting the patient against gravity, bathing, or brushing teeth. Like PSH following TBI, the attacks are difficult to prevent and/or treat. According to this review, published in Frontiers in Neurology, the underlying mechanisms causing these episodes in the degenerative process of CLN3 disease, are three-fold: (1) disturbed somatosensory modulation leading to a reduced threshold of pain; (2) degeneration within the neural anxiety/fear circuit leading to an imbalance of inhibition and excitation pathways; and (3) with advancing age, there appears a significant dominance of the sympathetic “fight or flight” neural system. Based on these observations, Prof. Ostergaard discusses a rational approach to prevent and/or treat the attacks. Read more here.

A novel role for CLN7 protein?  Loss of MFSD8 alters the secretome during Dictyostelium aggregation

Major facilitator superfamily domain-containing protein 8 (MFSD8) is a transmembrane protein that has been reported to function as a lysosomal chloride channel. In humans, homozygous mutations in MFSD8 cause a late-infantile form of NCL, CLN7 disease. Here, researcher Robert Huberman and colleagues at Trent University Ontario, Canada, used the amoeba Dictyostelium discoideum, to examine the effect of MFSD8-deficiency on the “secretome” (the overall secretory factors and proteins released from the cells) during the early stages of multicellular development. Results revealed that MFSD8 deregulates and disrupts protein secretion and protein localization within the cell, and/or causes the release of proteins not normally secreted by healthy cells. Interestingly, loss of MFSD8 was shown to alter the release of proteins also known to interact with CLN5, and loss of MFSD8 or CLN3 affected the release of common proteins. Together, this study published in the European Journal of Cell Biology, reveals the impact of MFSD8 loss on the secretome and lays the foundation for follow-up work that investigates the role of altered protein release in CLN7 disease. Read more here.