Tag Archives: preclinical research

Episode 33: Noema, Basimglurant and a New Clinical Trial for Seizures in TSC

February 7, 2022Uncategorizedclinical trials, epilepsy, epilepsy medication, epilepsy research, medical research, medications, preclinical research, seizures, TSC, TSC Alliance, TSC research, tuberous sclerosis complextsc-now

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In a very special early episode of TSC Now, host Dan Klein recognizes International #EpilepsyDay and the kickoff of the second annual Seizure Action Plan Awareness Week. In November 2020, a collaboration of three non-profit organizations, the TSC Alliance, Dravet Syndrome Foundation and Lennox-Gastaut Syndrome (LGS) Foundation, launched the Seizure Action Plan (SAP) Coalition to educate people with epilepsy, their caregivers and healthcare professionals about seizure emergency rescue protocols and the importance of personalized seizure action plans. As part of this effort the group is recognizing Seizure Action Plan Awareness Week (#SAPAW2022) to coincide with International Epilepsy Awareness Day on February 14.

This month’s episode is sponsored by Noema Pharma and explores their clinical trial to treat seizures common in TSC. A Swiss biotech company, Noema, is investigating a novel substance which has shown some positive effects in laboratory models related to tuberous sclerosis complex (TSC). The substance is called basimglurant, and it affects the activity of glutamate, an important molecule used by many neurons to communicate with other neurons in the brain, by acting on a receptor for glutamate called mGluR5. The company is setting up clinical trials to test whether the effect seen in the laboratory may also be seen in people.

First, to learn more about basimglurant and preclinical experiments underpinning the upcoming clinical trial, Dan spoke to Ype Elgersma, Professor of Molecular Neuroscience, Head of Research in the Department of Clinical Genetics, and Director of the ENCORE Expertise Center for Neurodevelopment Disorders at the Erasmus Medical Center In The Netherlands; and John Kemp, Former Chief Scientific Officer at Noema (02:28). They share what metabotropic glutamate receptor 5, or mGluR5, is and how increased activity at mGluR5 may lead to epilepsy; how negative modulators of this overactivity may be used as a treatment for epilepsy in TSC, and how Dr. Mustafa Sahin of Harvard Medical School tested this hypothesis in TSC mouse models. Findings from this study was published in 2018 in Neuropsychopharmacology.

Next, Dan spoke to Ali Mostajelean, MD, Associate Professor of Neurology, Director of the Epilepsy Service and Tuberous Sclerosis Clinic at UCSF Benioff Children’s Hospital; and George Garibaldi, Chief Medical Officer at Noema (07:55). They shared how Noema is using the findings in animal models as justification for a clinical trial and share how clinical studies using basimglurant for depression and Fragile X showed that the compound was safe in humans, albeit not as effective as researchers thought it would be in those disease states.

Finally, Dan spoke with Renata Lazarova, VP of Development, Pediatric Programs at Noema, and Steve Roberds, PhD, Chief Scientific Officer of the TSC Alliance (10:55), to learn what the clinical trial looks like, who can enroll, how Noema will determine whether the drug is efficacious and safe, and where people can find more information. Steve also talked about our partnership with Noema and how they worked with the TSC Alliance early on to solicit feedback from the TSC community and design a trial that both meets the needs of those with TSC and considers the quality of life of those participating.

Noema’s clinical study with their negative modulator of mGluR5 is currently participants across the US, Russia, Ukraine, Israel and Australia. For more information including the list of sites participating in the study, please contact Jo Anne Nakagawa at jnakagawa@tscalliance.org or (301) 562-9890.

Resources and Links
Learn more about International Epilepsy Day: https://internationalepilepsyday.org/
Learn more about the Seizure Action Plan Coalition and #SAPAW2022: https://seizureactionplans.org/
Learn more about epilepsy in TSC: https://www.tscalliance.org/about-tsc/signs-and-symptoms-of-tsc/brain-and-neurological-function/epilepsy-and-seizure-disorders/
Read an abstract of Dr. Sahin’s research looking at mGluR5 Modulation of Behavioral and Epileptic Phenotypes in a Mouse Model of Tuberous Sclerosis Complex: https://www.nature.com/npp/about?gclid=Cj0KCQiA34OBBhCcARIsAG32uvPcCBYuxzzlON-Xe9EikeYJD6XNNl8TDElaFiONa-02BSWFUv4w2voaAk6REALw_wcB

This episode is sponsored by:

Learn more about Noema Pharma: https://noemapharma.com/

Episode 31: The Present and Future of TSC & LAM Research

December 22, 2021Episodesclinical research, clinical trials, LAM, lymphangioleiomyomatosis, medical research, preclinical research, rare disease, The LAM Foundation, TSC, TSC Alliance, tuberous sclerosis, tuberous sclerosis complextsc-now

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In the final episode of TSC Now in 2021, host Dan Klein recaps the 2021 Virtual International TSC & LAM Research Conference: Driving Discoveries Beyond Boundaries, presented by Greenwich Biosciences and the Rothberg Institute of Childhood Diseases and co-hosted by the TSC Alliance® and The LAM Foundation. The conference brought together 179 people from 18 countries including researchers with a wide array of specialties and representing everything from basic to clinical science, who took part in plenary sessions, oral presentations, posters, and discussions around cross-cutting topics, including big data and clinical translation.

Dan chats with conference co-chairs Nishant Gupta, MD, Assistant Professor of Medicine at the University of Cincinnati, Director of the LAM Clinic Network, and Scientific Director of the LAM Foundation, and Rebecca Ihrie, PHD, Associate Professor of Cell and Developmental Biology and Neurosurgery at Vanderbilt University about their impressions of the conference overall, what topics they found most interesting and how the TSC and LAM research community can build off the momentum of the conference and foster the next generation of TSC and LAM researchers. Dan also asks them what areas of TSC and LAM research they find most exciting and what they think the future holds for the field.

Resources and Links:

Learn more about the research conference: https://www.tscalliance.org/researchers/research-conferences/
Download the conference program book: https://www.tscalliance.org/wp-content/uploads/2021/10/2021-Intl-TSC-LAM-Res-Conf-Program-Book.pdf
Learn more about the MILED clinical trial and how to get involved: https://www.thelamfoundation.org/MILED
Nominate a TSC Alliance community volunteer for one of our Volunteer of the Year Awards: https://www.tscalliance.org/news/submit-your-nominations-for-our-volunteer-of-the-year-awards/
Learn More about the 2022 World TSC Conference: https://www.tscalliance.org/2022-world-tsc-conference/ Conference registration Opens Monday, January 3, 2022
- Book your room for the conference today: https://book.passkey.com/gt/218256181?gtid=57f8b757a9eedc1e8f1572c336936050 You can also make a reservation by calling 1-800-774-1500 and using group code “TSC”

Episode 25: Lymphangioleiomyomatosis & Worldwide LAM Awareness Month (#WWLAM)

June 30, 2021Episodes#WWLAM, advocacy, clinical research, clinical trials, COVID-19, LAM, lung health, lymphangioleiomyomatosis, medical research, preclinical research, rare disease, The LAM Foundation, TSC, TSC Alliance, tuberous sclerosis, tuberous sclerosis complextsc-now

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In Episode 25 of TSC Now, host Dan Klein recognizes Worldwide LAM Awareness Month (#WWLAM) by focusing on lymphangioleiomyomatosis (LAM), a rare lung disease affecting women that is characterized by an abnormal growth of smooth muscle cells, especially in the lungs, lymphatic system and kidneys. LAM is caused by mutations in the same gene(s) as TSC and is a common manifestation for women with TSC but can also occur sporadically with no other TSC manifestations. To help raise awareness of LAM on the last day of Worldwide LAM Awareness Day, this episode will focus exclusively on LAM, research being done to develop new treatments and ultimately a cure, and the organization that is leading the charge to improve the lives of women with LAM in the US.

First, Dan talks to Sue Sherman, MHA, Chief Executive Officer of The LAM Foundation (02:18). The LAM Foundation was founded in 1995 by a mother of a woman with LAM with a mission to urgently seeks safe and effective treatments, and ultimately a cure, for lymphangioleiomyomatosis through advocacy and the funding of promising research. They are dedicated to serving the scientific, medical and patient communities by offering information, resources and a worldwide network of hope and support. They discuss how The LAM Foundation has changed over the years, how their investment in research has helped pave the way for breakthroughs, how the organization pivoted during the COVID-19 pandemic, and how they are raising awareness of LAM during Worldwide LAM Awareness month.

Next, Dan talks to Hilaire Lam, PhD (14:22), Research Associate in the Division of Pulmonary and Critical Care Medicine at Brigham and Women’s Hospital and an instructor in medicine at Harvard Medical School. The ultimate goal of Dr. Lam’s research is to leverage mTORC1-driven mitochondrial alterations to uncover therapeutic targets for TSC and LAM. She shares more about the aims of her research, how she first became interested in LAM, what gaps exist in our understanding of LAM and how researchers are currently looking to address those outstanding questions to develop new therapies. She also discusses how she is motivated by women living with LAM and how their relentlessness inspires her to help find a cure.

Earlier this month in recognition of Worldwide LAM Awareness Month, the TSC Alliance hosted an e-webinar titled “LAM in TSC: Surveillance, Treatment and Research” presented by Souheil Y. El-Chemaly, MD, Clinical Director of the Center for LAM Research and Clinical Care at Brigham and Women’s Hospital. The webinar covered surveillance, management and treatment recommendations based on the latest consensus guidelines, clinical trials currently taking place and a look to the future of research in LAM. A recording of the presentation will be available on our e-webinars website soon at tscalliance.org/e-webinars.

Resources and Links

Visit The LAM Foundation’s website: https://thelamfoundation.org/
Learn more about Worldwide LAM Awareness Month: https://thelamfoundation.org/WorldwideLAMAwarenessMonth
Learn more about LAM in TSC: https://www.tscalliance.org/about-tsc/signs-and-symptoms-of-tsc/lungs/
Follow The LAM Foundation on social media:
- Facebook – https://www.facebook.com/TheLAMFoundation
- Twitter – https://twitter.com/LAMFoundation
- Instagram – https://www.instagram.com/thelamfoundation/
- LinkedIn – https://www.linkedin.com/company/the-lam-foundation/
- YouTube – https://www.youtube.com/channel/UCYldYVWkpHqEvL0ETHND43g
Check out Journeys, a comprehensive blog on LAM research, patient advocacy, education and awareness provided by The LAM Foundation: https://thelamfoundation.org/Blog
Join The LAM Foundation Community to receive their emails: https://www.thelamfoundation.org/Take-Action/Join-The-LAM-Foundation-Community

Episode 17: Gene Therapy in TSC

October 31, 2020Episodesclinical trials, coronavirus, COVID-19, gene therapy, medical research, preclinical research, TSC, TSC research, TSCRP, tuberous sclerosis, Tuberous Sclerosis Alliance, tuberous sclerosis complextsc-now

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In episode 17 of TSC Now, host Dan Klein talks to Xandra Breakefield, PhD, Professor of Neurology at Harvard Medical School and a geneticist, specializing in neurology & tadiology at Massachusetts General Hospital. Dr. Breakefield’s research focuses on gene therapy in preclinical mouse models of TSC in which the TSC1 or TSC2 gene are missing. By introducing the missing gene into the bloodstream via an adeno-associated virus (AAV) vector, Dr. Breakefield has been able to normalize brain structures and extend the lifespan to almost normal length in mouse models of both TSC1 and TSC2. This research was funded in part by grants through the Tuberous Sclerosis Complex Research Program (TSCRP), demonstrating how funds appropriated because of the tireless advocacy during the March on Capitol Hill has meaningfully advanced TSC research. They discuss how AAV vector technology is already being used in other diseases, what are the potential benefits of gene therapy in TSC over current treatment options, and how to transition from ongoing preclinical trials to future clinical trials.

Resources and Links
Read more about Dr. Breakefield’s Research: https://cdmrp.army.mil/tscrp/research_highlights/19breakefield_highlight
Register now for the final Virtual TSC & LAM Conference and view tracks from the previous two: https://www.tsalliance.org/news/join-us-for-the-2020-virtual-tsc-lam-conference-series/
Visit the Virtual Exhibit Hall: https://www.tsalliance.org/virtual-exhibit-hall/
Learn more about a clinical study for individuals with TSC who contracted COVID-19: https://www.tsalliance.org/tsc-matters/have-you-or-your-loved-one-with-tsc-been-diagnosed-with-covid-19-2/