ION283 for Lafora Disease

(Lafora Trial)

Overseen By Kristy Riddle, RN, BSN

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Berge Minassian

Must not be taking: Antiplatelets, Anticoagulants

Disqualifiers: HIV, Hepatitis, Renal impairment, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ION283 for Lafora disease, a rare genetic condition that causes seizures and muscle problems. The goal is to determine if ION283 is safe and effective when administered through a spinal injection. Individuals aged 10 to 18 with a confirmed genetic diagnosis of Lafora disease who can walk at least 10 steps independently are eligible to participate. All participants will receive the same dose of ION283 to evaluate its effects. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial requires that you stop using antiplatelet or anticoagulant medications (blood thinners) like clopidogrel, warfarin, and others at least 14 days before starting the study, except for low-dose aspirin. Other medications are not specifically mentioned, so it's best to discuss your current medications with the study team.

Is there any evidence suggesting that ION283 is likely to be safe for humans?

Research has shown that ION283, the treatment being tested for Lafora Disease, has been administered to patients before. This drug is injected into the spinal fluid. Patients have tolerated this treatment well, with no serious side effects reported in earlier studies.

Since this study is in the early stages, it focuses on assessing the treatment's safety for humans. The trial's progression indicates that ION283 has shown enough promise in earlier research to advance. While mild side effects may occur, the main goal is to ensure safety and evaluate its effectiveness in treating Lafora Disease.

In summary, ION283 has been tested before, and patients have tolerated it well so far. This study will continue to ensure its safety for use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about ION283 for Lafora disease because it targets the genetic roots of the condition, offering a new approach. Unlike current treatments that mainly focus on managing symptoms like seizures, ION283 is designed to interfere with the production of toxic glycogen molecules that accumulate in the brain due to a genetic mutation. This innovative mechanism could potentially slow down or halt disease progression rather than just alleviating symptoms. By directly targeting the underlying cause of Lafora disease, ION283 holds promise for more effective long-term management.

What evidence suggests that ION283 might be an effective treatment for Lafora disease?

Research has shown that ION283 may help treat Lafora disease, a rare type of epilepsy. Early findings suggest that ION283 could slow the disease's progression. In this trial, all participants with Lafora disease will receive ION283 through direct injection into the spinal fluid, enhancing its delivery to the brain. Although more data is being collected, initial results are promising and indicate potential in slowing the disease's progression. Further studies are necessary to confirm these effects, but there is hope that ION283 could benefit patients with Lafora disease. ^{1 2 3 6 7}

Who Is on the Research Team?

Berge Minassian, MD

Principal Investigator

UT Southwestern Medical Center

Are You a Good Fit for This Trial?

This trial is for children aged 10-18 with genetically confirmed Lafora disease, able to walk independently and have an LDPS score ≥ 9. They must not be pregnant or breastfeeding, agree to avoid donating sperm/eggs, use effective contraception if applicable, and comply with study requirements. Exclusions include those unwilling to undergo lumbar puncture, recent drug/alcohol abuse, certain medical conditions like uncontrolled hypertension or coagulopathy, and those on specific medications.

Inclusion Criteria

I can walk 10 steps on my own and have a high level of physical disability.

I agree not to donate sperm/eggs from signing the consent until 12 weeks after the last study drug dose.

My diagnosis of Lafora disease is confirmed through genetic testing.

Exclusion Criteria

I cannot or do not want to have a lumbar puncture.

I have no major health issues found in my medical exams.

I am willing to follow the study's procedures and cooperate with the research team.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive 15 mg ION283 intrathecal bolus injection every 12 weeks

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ION283

Trial Overview The trial tests the safety and effectiveness of ION283 given as intrathecal injections in patients with Lafora Disease. All participants will receive a dose of 15 mg through lumbar puncture. The focus is on multiple dosing sessions to evaluate how well the treatment works over time.

How Is the Trial Designed?

Group I: ION283 Arm Experimental Treatment 1 Intervention

Open label evaluation of ION283. All subjects with Lafora disease enrolled in this study will receive ION283.

Who Is Running the Clinical Trial?

Berge Minassian

Lead Sponsor

Trials

1

Recruited

10+

Elpida Therapeutics SPC

Industry Sponsor

Trials

4

Recruited

60+

Published Research Related to This Trial

Inositol 1,4,5-trisphosphate (InsP3) metabolism is significantly reduced in cerebellar tissues of patients with olivopontocerebellar atrophy (OPCA) and in Lurcher mutant mice, indicating a potential link between impaired InsP3 metabolism and neuronal degeneration.

The study found that in young Lurcher mice, InsP3 metabolism was about 40% of normal levels, and nearly absent in older Lurcher mice, suggesting that decreased InsP3 metabolism may contribute to the progression of cerebellar ataxia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inositol 1,4,5-trisphosphate metabolism in the cerebella of Lurcher mutant mice and patients with olivopontocerebellar atrophy. Vig, PJ., Subramony, SH., Currier, RD., et al.[2019]

Injecting inositol 1,4,5-trisphosphate (InsP3) into specific neurons of Aplysia kurodai triggers an outward current that is linked to an increase in potassium conductance, indicating that InsP3 plays a crucial role in mobilizing calcium from internal stores to activate this current.

The outward current induced by InsP3 is sensitive to tetraethylammonium (TEA) and is dependent on intracellular calcium levels, suggesting that InsP3 acts as a second messenger to facilitate calcium's role in neuronal signaling.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ionic mechanism of the outward current induced by intracellular injection of inositol trisphosphate into Aplysia neurons. Sawada, M., Ichinose, M., Maeno, T.[2019]

InsP3, when photolytically released in Purkinje neurons, can effectively induce long-term depression (LTD) similar to the activation of parallel fibers, highlighting its crucial role in synaptic plasticity.

The study found that both InsP3-induced LTD and LTD from parallel fiber activation share a common pathway, as they could not be further enhanced by each other, indicating that InsP3 receptors are essential for LTD induction in physiological conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induction of long-term depression and rebound potentiation by inositol trisphosphate in cerebellar Purkinje neurons. Khodakhah, K., Armstrong, CM.[2019]

The enzyme inositol polyphosphate 4-phosphatase, purified 3390-fold from calf brain, specifically hydrolyzes inositol 1,3,4-trisphosphate (Ins(1,3,4)P3) and inositol 3,4-bisphosphate (Ins(3,4)P2), producing inositol 1,3-bisphosphate and inositol 3-phosphate, indicating its role in inositol phosphate metabolism.

This enzyme operates optimally at a pH of 6.5 to 7.5 and is not inhibited by common ions like Li+, Ca2+, or Mg2+ at lower concentrations, suggesting a favorable safety profile for potential therapeutic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The isolation and characterization of inositol polyphosphate 4-phosphatase. Bansal, VS., Caldwell, KK., Majerus, PW.[2021]

Ins(1,3,4,6)P4 effectively releases calcium ions (Ca2+) in a dose-dependent manner, with a half-maximal effect concentration (EC50) of approximately 5.92 microM, although its maximal response is lower than that of Ins(1,4,5)P3.

In contrast, DL-Ins(1,3,4,5)P4 does not significantly influence Ins(1,4,5)P3-mediated Ca2+ release, suggesting it operates through a different receptor mechanism, highlighting the complexity of calcium signaling pathways in neuroblastoma cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interactions between inositol tris- and tetrakis-phosphates. Effects on intracellular Ca2+ mobilization in SH-SY5Y cells. Gawler, DJ., Potter, BV., Gigg, R., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06609889

A Safety and Efficacy of Intrathecally Administered ION283 ... A Phase 1/2 Open Label Study to Evaluate the Safety and Efficacy of Intrathecally Administered ION283 in Patients with Lafora Disease.

2. chelseashope.org chelseashope.org/safety-study/

ION283 Safety Study: ASO therapy for Lafora disease In order to show that the drug is effective, we need data that shows that patients remain stable over a significant period of time without the disease ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06609889?cond=Lafora%20Disease&rank=1

A Safety and Efficacy of Intrathecally Administered ION283 ... A Phase 1/2 Open Label Study to Evaluate the Safety and Efficacy of Intrathecally Administered ION283 in Patients with Lafora Disease.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12552056/

Neurofilament Light Chain as a Biomarker of Disease ... Lafora disease (LD) is a severe, ultra-rare childhood-onset progressive myoclonus epilepsy caused by biallelic pathogenic variants in either ...

5. withpower.com withpower.com/trial/phase-2-lafora-disease-9-2024-7ac56

ION283 for Lafora Disease This study will test the safety and efficacy of multiple doses of ION283 administered as intrathecal (IT) injections by lumbar puncture (LP).

6. synapse.patsnap.com synapse.patsnap.com/drug/2b6a096cdb6c4efcbc0182a4800d9ab9

ION-283 - Drug Targets, Indications, Patents A Phase 1/2 Open Label Study to Evaluate the Safety and Efficacy of Intrathecally Administered ION283 in Patients With Lafora Disease. 100 Clinical Results ...

7. ctv.veeva.com ctv.veeva.com/study/a-safety-and-efficacy-of-intrathecally-administered-ion283-in-patients-with-lafora-disease

A Safety and Efficacy of Intrathecally Administered ION283 in ... This study will test the safety and efficacy of multiple doses of ION283 administered as intrathecal (IT) injections by lumbar puncture (LP).