November 2023                                                                            Volume 34, Issue 11

Your voices guide our work.

Your gifts to the BDSRA Foundation propel action.

This holiday season, help support Batten families by donating to BDSRA.

This Toolbox Tuesday video breaks down the many ways you can give to the BDSRA Foundation this holiday season. Thank you in advance for investing in our mission and sharing our long-term vision of a world without Batten. 

From copy paper to personnel, $5 Fridays is designed to keep the office moving. The more $5 Friday donations BDSRA Foundation receives for operations, the more money BDSRA can invest in programs, research, and advocacy.

What is the impact created by your $5 Friday gift? It’s storing and mailing books to educators, packing up virtual party kits, and keeping all the conference supplies.

A $5 donation helps secure BDSRA’s technology needs, which provides crucial communication and programming for Batten families, such as Ask-An-Expert webinars, virtual parties, and international meetings.

By giving $5 on Fridays, you help ensure Batten families receive family resources, Batten Disease Awareness Day T-shirts, and activity kits for virtual parties.

Communicating with our Batten community is vital to our mission. Your $5 Friday donation ensures that Batten families and the community’s voices will be heard.

Your $5 Friday donation ensures BDSRA database needs, which include sending The Illuminator newsletter each month and managing the Family Register.

These are the power of FIVE. 

So, you have just signed up for our Fam Funds program; what happens now?

Search your inbox for an email from Database Manager Noah Siedman, who gives helpful tips in the tutorial above on what you’ll need to do next.

Watch the full tutorial on our website by clicking the button below.

Office Manager Linda Barkhurst has been working for BDSRA for two years now and gives thanks to the Batten community.

The 2023 BDSRA Annual Family Conference was the first time Database Manager Noah Siedman met Batten families in person. The interactions and the community’s togetherness are among his 2023 highlights.

Through his role at BDSRA, Marketing & PR Coordinator Patrick Kotnik has utilized the power of storytelling alongside the Batten community.

From across the globe in Australia, BDSRA Head of Research & Medical Affairs Dr. Ineka Whiteman, alongside her daughter, Ariella, gives thanks to her family and the Batten community that has also become her family.

President & CEO Amy Fenton Parker expresses how thankful she is for the Batten community’s engagement and participation.

HB177, the co-pay accumulator bill, passed out of committee on November 15.  The next step is to get it on the House Floor for passage.

BDSRA encourages Ohio residents to copy the message below and email it to Ohio House Speaker Jason Stephens at rep93@ohiohouse.gov to advocate for this bill to get to the house floor.

Dear Speaker Stephens,

During the November 15th hearing of the Public Health Policy Committee, HB177 – to prohibit certain health insurance cost-sharing practices – was passed out of committee unanimously. This bill passed the House Floor unanimously last GA, but advocates ran out of time to get the Senate to act before the end of the 134th GA. We are asking that you act quickly, so we have ample time to educate the Senators on the importance of passing this legislation in Ohio.

Ohioans are being harmed by these predatory practices and it is time for the legislature to act to protect the most vulnerable patients. Similar bills have now been passed in 19 states and have shown no evidence of increasing premium costs but have protected thousands of patients from increasing out-of-pocket costs.

This bill has an active coalition of over 60 patient and provider groups working on this bill and we urge you to bring it to the House Floor for a vote as soon as you schedule your next Session.

Sincerely,

HB291 – Non-Medical Switching – will have a hearing in the House Insurance Committee next week.

If you have been impacted and would be interested in testifying, Randi Clites, a patient advocate, is happy to help you draft your testimony. Rep Dr. Liston would like to have at least two patients testify, as she has a physician who will be testifying.

If you are interested in submitting testimony, it will be due by Tuesday morning, but you should try to get it in by Monday 5 p.m. EST.

Submit testimony to Rep70@ohiohouse.gov and the subject line should be HB291 written testimony or if you plan to testify in person IN PERSON in caps.

A link to the committee is below, where you can find the sponsor testimony that will provide you an outline for written testimony. Click the button below to access the document to submit testimony to the chair’s office.

Insurance Committee | Ohio House of Representatives

Click below to read the letters BDSRA signed on to in November:

• Coalition letter for support of Ohio HB177 to be scheduled for a floor vote

• FY24 Epilepsy Appropriations Organizational Support Letter

• Letter of support urging Congress to consider small technical corrections to the IRA’s orphan drug exclusion provisions that would benefit the rare disease community
  • One-Pager Explanation

Mark your calendars for Wednesday, Dec. 13 at 6 p.m. EST (Thursday, Dec. 14, 2023, at 10 AM AEDT, Sydney/Melbourne) for a 2023 Research in Review webinar hosted by Dr. Ineka Whiteman, joined by Dr. David Pearce, Dr. Jonathan Cooper, Dr. Kourtney Santucci, and Dr. Tony Cook.

Register by clicking the button below.

If you missed the REGENXBIO webinar, check it out on the BDSRA YouTube channel! The event featured the latest news on REGENXBIO’s Batten disease programs along with a Q&A.

Click the button below to watch.

How would you describe your Batten journey in one word?

1. Click the button below to download and print out the sheet above.
2. Write down your word.
3. Send an email to BDSRA Foundation Marketing & PR Coordinator Patrick Kotnik at patrick@bdsrafoundation.org detailing why you chose the word you wrote down.
4. You can either hold up the sheet and record a video of yourself explaining why you chose the word you wrote or write about it in the email.
5. Whether you choose to write about it or record a video, please take a picture of yourself holding up the sheet and attach it to the email.

The BDSRA Foundation is committed to supporting and advocating for patients and families of all CLN types to raise awareness and give the Batten community a platform to share their stories. This elevates our three pillars — Support, Research, and Advocacy.

Please contact BDSRA Foundation Marketing & PR Coordinator Patrick Kotnik at patrick@bdsrafoundation.org with any questions.

Shared your story with local media? Let us know! Email Patrick and we will share.

Do You Follow BDSRA on Social Media?

Want to see more content from BDSRA? Don’t miss out on upcoming events, information, campaigns, and community posts! Follow @BDSRA on Facebook, Instagram, LinkedIn, X, and YouTube to stay in the know on all things happening in our Batten Community!

Click below to follow all of our accounts: 

As part of this year’s Annual  Family Conference program in July, we hosted the inaugural  NCL Researchers Challenge. Batten disease researchers from all over the world were invited to enter a “three-minute thesis” style video presentation, summarizing their team’s main research approach, latest findings, and what the significance of these findings is for our Batten community. Conference registrants were invited to view and vote for their favorites. It was so wonderful to see the level of interest and engagement from both the research and family communities!

Congratulations to Dr. Joshua T. Dearborn, Instructor of Medicine, Washington University School of Medicine in St Louis (WUSTL), who was awarded second place for his presentation: Medical Marijuana and Batten Disease. We recently interviewed Dr. Dearborn to learn more about this exciting research.

1. Please tell us a bit about your team at WUSTL and the research carried out in your lab.

Our team that works on the NCL-related seizure projects is made up of myself, Dr. Mark Sands, Dr. Michael Wong, Nick Rensing, Dr. Keigo Takahashi, and Dr. Jonathan Cooper. I’ve worked as part of a team with Dr. Mark Sands since 2014. Generally speaking, we use mouse models of lysosomal storage disorders to do two things: understand the nature and progression of these diseases and try to correct disease-related pathology and symptoms. We have studied a mouse model of CLN1 for many years, applying such treatments as gene therapy, enzyme replacement, and bone marrow transplant. Recently, I’ve undertaken the study of a CLN2 mouse model.

Attendees (in-person and virtually) came together in Sioux Falls, South Dakota for the inaugural Batten Center of Excellence Program meeting.

On November 10, members of the Batten clinical community, board members, and BDSRA staff came together from Australia to North Carolina, to reimagine a national Batten Center of Excellence (CoE) program.

Following our call for applications in September, we were beyond delighted and humbled to have received applications from 11 institutions from around the U.S., seeking to join our CoE Program. It was a highly productive day, with focused, energized discussions, a genuinely collaborative vibe, and the group sharing a unified vision for a program that aims to optimize patient outcomes and quality of life for individuals affected by Batten disease and their families. This first class of applicants will work together under the auspices of the BDSRA Foundation, to co-design and implement the best possible CoE model, that will increase patient access to the best possible standardized, evidence-based multidisciplinary care and clinical services through a national network of Centers.

Meetings will be held regularly from now until July 2024, to develop and implement the Centers of Excellence Program, according to the timeline below. Stay tuned to our social media and The Illuminator for further updates in the coming months.

Centers of Excellence Program: Development and Implementation Timeline

Our sincerest thanks to all our applicants and meeting attendees. We are grateful for your care, expertise, and dedication to our Batten families and community.

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

On November 8, REGENXBIO announced in a press release its intention to halt the development of potential AAV gene therapies for multiple programs, including the RGX-181 and RGX-381 programs for the treatment of CNS and ocular manifestations of CLN2 disease, respectively.

We worked swiftly with our global patient advocacy partners to issue a joint statement on this matter, a copy of which can be read here.

REGENXBIO has assured us that it will be actively exploring a range of partnership opportunities to enable the continuing development of its CLN2 gene therapy programs. Through ongoing discussions this month, including with President and CEO Ken Mills, we have been encouraged to hear REGENXBIO is indeed taking proactive and practical steps in seeking solutions for the programs – and we will continue to support and urge them for as long as it takes.

On Thursday, November 30, the BDSRA Foundation hosted an open webinar to share the latest updates on REGENXBIO’s CLN2 disease programs, followed by a Q&A. You can watch a recording of this event by clicking the button below.

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.

• 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.

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.

Have you completed the Family Register form?

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 2-3 minutes to complete and can be accessed by clicking the button below.

Thank you for participating in this important initiative!

Rus CM, Polla DL, Di Bucchianico S, Fischer S, Hartkamp J, Hartmann G, Alpagu Y, Cozma C, Zimmermann R, Bauer P. Sci Rep. 2023 Oct 29;13(1):18550.

Abstract

Neuronal ceroid lipofuscinosis 6 (CLN6) is a rare and fatal autosomal recessive disease primarily affecting the nervous system in children. It is caused by a pathogenic mutation in the CLN6 gene for which no therapy is available. Employing an untargeted metabolomics approach, we analyzed the metabolic changes in CLN6 subjects to see if this system could potentially yield biomarkers for diagnosis and monitoring disease progression. Neuronal-like cells were derived from human fibroblast lines from CLN6-affected subjects (n = 3) and controls (wild type, n = 3). These were used to assess the potential of a neuronal-like cell-based metabolomics approach to identify CLN6 distinctive and specific biomarkers. The most impacted metabolic profile is associated with sphingolipids, glycerophospholipids metabolism, and calcium signaling. Over 2,700 spectral features were screened, and fifteen metabolites were identified that differed significantly between both groups, including the sphingolipids C16 GlcCer, C24 GlcCer, C24:1 GlcCer and glycerophospholipids PG 40:6 and PG 40:7. Of note, these fifteen metabolites were downregulated in the CLN6 disease group. This study is the first to analyze the metabolome of neuronal-like cells with a pathogenic mutation in the CLN6 gene and to provide insights into their metabolomic alterations. This could allow for the development of novel biomarkers for monitoring CLN6 disease.

Read the full article here.

Murray SJ, Wellby MP, Barrell GK, Russell KN, Deane AR, Wynyard JR, Gray SJ, Palmer DN, Mitchell NL. Front Pharmacol. 2023 Oct 24;14:1212235.

Abstract

Mutations in the CLN5 gene cause the fatal, pediatric, neurodegenerative disease CLN5 neuronal ceroid lipofuscinosis. Affected children suffer progressive neuronal loss, visual failure, and premature death. Presently there is no treatment. This study evaluated dual intracerebroventricular (ICV) and intravitreal (IVT) administration of a self-complementary adeno-associated viral vector encoding ovine CLN5 (scAAV9/oCLN5) into CLN5-affected sheep (CLN5-/-) at various disease stages. CLN5 disease progression was slowed in pre-symptomatic sheep who received a moderate dose of scAAV9/oCLN5, whilst a higher ICV dose treatment in early and advanced symptomatic animals delayed or halted disease progression. Intracranial (brain) volume loss was attenuated in all treatment cohorts, and visual function was also sustained in both the early and advanced symptomatic treated sheep over the 24-month duration of the study. Robust CLN5 protein expression was detected throughout the brain and spinal cord, and improvements in central nervous system and retinal disease correlates were observed. These findings hold translational promise for extending and improving the quality of life in both pre-symptomatic and symptomatic CLN5 patients and prompted the initiation of the first in-human Phase I/II clinical trial testing ICV/IVT administration of scAAV9 encoding human CLN5 (https://clinicaltrials.gov/study/NCT05228145).

Read the full article here.

N. Gammaldi, F. Pezzini, E. Michelucci, N. Di Giorgi, A. Simonati, S. Rocchiccioli, F.M. Santorelli, S. Doccini. Neurobiology of Disease. 2023, 189: 106349

Abstract

Neuronal ceroid lipofuscinosis (NCL) is a group of neurodegenerative disorders whose molecular mechanisms remain largely unknown. Omics approaches are among the methods that generate new information on modifying factors and molecular signatures. Moreover, omics data integration can address the need to progressively expand knowledge around the disease and pinpoint specific proteins to promote as candidate biomarkers. In this work, we integrated a total of 62 proteomic and transcriptomic datasets originating from humans and mice, employing a new approach able to define dysregulated processes across species, stages, and NCL forms. Moreover, we selected a pool of differentially expressed proteins and genes as species- and form-related biomarkers of disease status/progression and evaluated local and spatial differences in most affected brain regions. Our results offer promising targets for potential new therapeutic strategies and reinforce the hypothesis of a connection between NCLs and other forms of dementia, particularly Alzheimer’s disease.

Read the full article here.

Nickel M, Gissen P, Greenaway R, Cappelletti S, Hamborg C, Ragni B, Ribitzki T, Schulz A, Tondo I, Specchio N. Neuropediatrics. 2023 Dec;54(6):402-406.

Abstract

Neuronal ceroid lipofuscinosis type 2 (CLN2 disease) is a rare pediatric disorder associated with rapid neurodegeneration and premature death in adolescence. An effective enzyme replacement therapy (cerliponase alfa) has been approved that can reduce this predictable neurological decline. The nonspecific early symptoms of CLN2 disease frequently delay diagnosis and appropriate management. Seizures are generally recognized as the first presenting symptom of CLN2 disease, but emerging data show that language delay may precede this. An improved understanding of language deficits in the earliest stage of CLN2 disease may support the early identification of patients. In this article, CLN2 disease experts examine how language development is affected by CLN2 disease in their clinical practices. The authors’ experiences highlighted the timings of first words and first use of sentences, and language stagnation as key features of language deficits in CLN2 disease, and how deficits in language may be an earlier sign of the disease than seizures. Potential challenges in identifying early language deficits include assessing patients with other complex needs and recognizing that a child’s language abilities are not within normal parameters given the variability of language development in young children. CLN2 disease should be considered in children presenting with language delay and/or seizures to facilitate earlier diagnosis and access to treatment that can significantly reduce morbidity.

Read the full article here.

Kovács AD, Gonzalez Hernandez JL, Pearce DA*. Sci Rep. 2023 Nov 6;13(1):19229.

*BDSRA Foundation Board Member, Dr. David Pearce

Abstract

Batten disease is a group of mostly pediatric neurodegenerative lysosomal storage disorders caused by mutations in the CLN1-14 genes. We have recently shown that acidified drinking water attenuated neuropathological changes and improved motor function in the Cln1R151X and Cln3-/- mouse models of infantile CLN1 and juvenile CLN3 diseases. Here we tested if acidified drinking water has beneficial effects in Cln2R207X mice, a nonsense mutant model of late infantile CLN2 disease. Cln2R207X mice have motor deficits, muscle weakness, develop tremors, and die prematurely between 4 and 6 months of age. Acidified water administered to Cln2R207X male mice from postnatal day 21 significantly improved motor function, restored muscle strength, and prevented tremors as measured at 3 months of age. Acidified drinking water also changed disease trajectory, slightly delaying the death of Cln2R207X males and females. The gut microbiota compositions of Cln2R207X and wild-type male mice were markedly different and acidified drinking water significantly altered the gut microbiota of Cln2R207X mice. This suggests that gut bacteria might contribute to the beneficial effects of acidified drinking water. Our study demonstrates that drinking water is a major environmental factor that can alter disease phenotypes and disease progression in rodent disease models.

Read the full article here.

We are sorry to say that Facebook has changed its fundraising policy and is no longer paying processing fees or handling its own fundraising initiatives. They have engaged the PayPal Giving Fund to process payments, and we will be charged processing fees.

Additionally, PayPal Giving Fund erroneously denied our organization the ability to fundraise on Facebook saying that we were not eligible for charitable donations, even though PayPal processes donations to BDSRA Foundation routinely. (EIN 91-1397792)

We have sent all the necessary paperwork to PayPal, and they have not responded. If you would like to donate or promote donations to BDSRA Foundation tomorrow, you may go directly to our website at https://bdsrafoundation.org/donation/

We are grateful for the many fundraisers our community organizes for us. We will continue to work to get this resolved. If you have any questions or concerns, please contact me at Amy@BDSRAFoundation.org or 614-973-6011.

In Loving Memory 

Remember those we have lost to Batten disease. We work daily to build a brighter future for families in their honor and memory.

Brock “Cowboy Brock” Richard Scarpetta | April 9, 2007 – October 10, 2023

Kyndel Dawn Roop | March 31, 2015 – November 8, 2023

To have your loved one’s name placed in The Illuminator and read at the memorial service at the Annual Family Conference in July, please email patrick@bdsrafoundation.org.

Thank You BDSRA Community of Donors!

Thank you for investing in our mission. We exist to provide support, research, and advocacy for families with all forms of Batten disease. We want to acknowledge the donors who gave so generously last month to our work. Together, we are Batten Advocates for a Cure.

To view the list of recent donors, please click the button below!

We connect your donation to Support, Research, and Advocacy for families of all CLN types.

BDSRA Foundation

PO Box 30049
Gahanna, OH 43230

(800) 448-4570 | info@bdsrafoundation.org | www.bdsrafoundation.org

View The Illuminator online