Stem Cell Therapy for Inherited Metabolic Brain Diseases

(DUOC-01 Trial)

Overseen By PTCT Referrals

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Joanne Kurtzberg, MD

Must not be taking: Immunosuppressives, Chemotherapy

Disqualifiers: Prior transplant, Seizures, HIV, others

Stay on Your Current Meds You can continue your current medications while participating

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new stem cell treatment called DUOC-01 for individuals with certain inherited metabolic brain diseases. The main goal is to determine the safety and effectiveness of this treatment when combined with a standard procedure known as umbilical cord blood transplantation. The trial seeks participants diagnosed with specific conditions like Adrenoleukodystrophy or Tay Sachs disease who have shown signs of brain involvement, such as behavioral difficulties or sleep problems. Participants must also be undergoing treatment with umbilical cord blood transplantation. As a Phase 1 trial, this research aims to understand how DUOC-01 works in people, offering participants the opportunity to be among the first to receive this innovative treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that you cannot participate if you are receiving certain treatments like radiotherapy, immunosuppressive medications, or cytotoxic chemotherapy.

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

Research has shown that DUOC-01, a treatment made from cord blood cells, is under study to determine its safety when used alongside other treatments for certain brain diseases. DUOC-01 aims to deliver donor cells to the brain more quickly in children also receiving a cord blood transplant.

In earlier studies, DUOC-01 showed promise when combined with standard treatments. However, detailed safety information from human trials remains limited. This trial is in its early stage, focusing primarily on assessing the safety of DUOC-01 in people. This phase typically involves a smaller number of participants to closely monitor any side effects.

If DUOC-01 proves safe in this phase, it could lead to further studies with larger groups to better understand its effectiveness. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for inherited metabolic brain diseases, which typically involve enzyme replacement or gene therapy, DUOC-01 uses stem cell therapy to target the brain differently. Researchers are excited about DUOC-01 because it is derived from stem cells found in umbilical cord blood, offering a novel way to potentially repair or replace damaged cells in the brain. This treatment is administered intrathecally, meaning directly into the spinal canal, which could enhance its ability to reach the brain more effectively than traditional methods. The unique approach of using stem cells could pave the way for more targeted and efficient treatments for these complex conditions.

What evidence suggests that DUOC-01 might be an effective treatment for inherited metabolic brain diseases?

Research has shown that DUOC-01, which participants in this trial will receive, could be a promising new cell therapy for treating inherited metabolic diseases affecting the brain. This treatment delivers donor cells to the brain more quickly, potentially improving outcomes for children receiving cord blood transplants. Early studies suggest that DUOC-01 helps these cells integrate better into the brain and spinal cord. Although this method is new, promising lab research supports DUOC-01's potential to aid in brain repair for these conditions. ^{1 2 6 7 8}

Who Is on the Research Team?

Joanne Kurtzberg, MD

Principal Investigator

Duke University

Are You a Good Fit for This Trial?

This trial is for children and young adults (1 week to <21 years old) with certain inherited metabolic brain diseases, who can perform daily activities at least 40% of the time. They should have a life expectancy over 6 months, specific enzyme or mutation-confirmed diseases, signs of disease in their nervous system, and good heart, liver, kidney, and lung function. A matching umbilical cord blood unit for transplant must be available.

Inclusion Criteria

My disease shows up on brain scans or affects my nervous system.

My kidney, liver, heart, and lung functions are all within normal ranges.

My genetic condition was confirmed by two separate tests.

Exclusion Criteria

Pregnant or breastfeeding.

Inability to obtain patient's, parent's or legal guardian's consent.

You cannot have an MRI scan or lumbar puncture.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo unrelated umbilical cord blood transplantation (UCBT) followed by intrathecal administration of DUOC-01 between day 26 and 28 post-transplant

4 weeks

Multiple visits for transplantation and intrathecal administration

Follow-up

Participants are monitored for safety and effectiveness, including evaluations for infusional and neuro toxicity, and standard of care follow-up evaluations

1-5 years

Regular follow-up visits for evaluations

What Are the Treatments Tested in This Trial?

Interventions

• DUOC-01

Trial Overview The study tests the safety and feasibility of DUOC-01 cells given into the spinal fluid as an extra treatment during standard unrelated cord blood transplants in patients with early signs of demyelinating disease due to inherited metabolism errors.

How Is the Trial Designed?

Group I: Intrathecal administration of DUOC-01 Experimental Treatment 1 Intervention

Administration of DUOC-01, given intrathecally, between day 26 and 28 post unrelated cord blood transplant

Who Is Running the Clinical Trial?

Joanne Kurtzberg, MD

Lead Sponsor

Trials

19

Recruited

710+

The Marcus Foundation

Collaborator

Trials

19

Recruited

2,200+

Published Research Related to This Trial

Mucopolysaccharidosis type IIIA is caused by a deficiency of the sulfamidase enzyme, leading to harmful heparan sulfate buildup and severe neurological issues, highlighting the need for effective treatments.

Genetically modified embryonic stem cells can be engineered to produce high levels of lysosomal enzymes, potentially offering a renewable source of cells for therapy in lysosomal storage disorders, which can be tested in animal models before clinical application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Directed differentiation and characterization of genetically modified embryonic stem cells for therapy. Lau, AA., Hemsley, KM., Meedeniya, A., et al.[2008]

A new human induced pluripotent stem cell (iPSC) line was created from a Pompe disease patient, which can help researchers study the disease and develop new treatments.

This iPSC line is particularly valuable because it comes from a patient with a specific mutation in the GAA gene, allowing for targeted disease modeling and drug discovery efforts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A human induced pluripotent stem cell line (TRNDi007-B) from an infantile onset Pompe patient carrying p.R854X mutation in the GAA gene. Cheng, YS., Li, R., Baskfield, A., et al.[2020]

Researchers developed an induced pluripotent stem cell (iPSc) model of Gaucher's disease (GD) that retains the disease's genetic mutations and low enzyme activity, allowing for effective study of the neuronopathic form of the disease.

Using this iPSc model, they identified two nojirimycin analogues that can increase acid-β-glucosidase activity, suggesting potential therapeutic options for treating neuronopathic GD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuronopathic Gaucher's disease: induced pluripotent stem cells for disease modelling and testing chaperone activity of small compounds. Tiscornia, G., Vivas, EL., Matalonga, L., et al.[2021]

Embryonic stem cell-derived glial precursors engineered to overexpress human arylsulfatase A (hASA) showed a significant increase in enzyme activity, up to 30-fold, and effectively differentiated into brain cells, indicating their potential for gene therapy.

In a mouse model of metachromatic leukodystrophy, transplantation of these engineered cells resulted in a 46.7% reduction of harmful sulfatide deposits in the brain, demonstrating their efficacy in correcting metabolic defects associated with the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Embryonic stem cell-based reduction of central nervous system sulfatide storage in an animal model of metachromatic leukodystrophy. Klein, D., Schmandt, T., Muth-Köhne, E., et al.[2012]

Researchers created a new induced pluripotent stem cell (iPSC) line from a 19-year-old female with Fanconi Bickel Syndrome (FBS), which is caused by mutations in the SLC2A2 gene responsible for GLUT2, a glucose transporter.

This iPSC line can be used as a valuable model to study the mechanisms of FBS and to explore potential new treatments for the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Derivation of a human induced pluripotent stem cell line (QBRIi007-A) from a patient carrying a homozygous intronic mutation (c.613-7T>G) in the SLC2A2 gene. Elsayed, AK., Aghadi, M., Al-Khawaga, S., et al.[2022]

Two human-induced pluripotent stem cell lines (hiPSCs) were successfully created from the blood cells of a mother and son with Fabry disease, providing a unique model to study this genetic disorder.

These hiPSCs exhibited normal characteristics of stem cells and can differentiate into various cell types, which may help researchers better understand the disease mechanisms and develop potential therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human-induced pluripotent stem cell lines (CMCi006-A and CMCi007-A) from a female and male patient with Fabry disease carrying the same frameshift deletion mutation. Cui, S., Shin, YJ., Ko, EJ., et al.[2021]

Patient-derived neural stem cells from individuals with Pompe disease displayed key disease characteristics, such as glycogen accumulation and increased lysosomal staining, making them a valuable model for studying the disease and testing treatments.

Treatment with recombinant human acid alpha-glucosidase (rhGAA) and a combination of hydroxypropyl-β-cyclodextrin and δ-tocopherol effectively reduced disease-related phenotypes in these neural stem cells, suggesting potential therapeutic strategies for addressing CNS involvement in Pompe disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modeling CNS Involvement in Pompe Disease Using Neural Stem Cells Generated from Patient-Derived Induced Pluripotent Stem Cells. Cheng, YS., Yang, S., Hong, J., et al.[2021]

A new induced pluripotent stem cell (iPSC) line was created from an 11-day-old girl with maple syrup urine disease type Ib, which is caused by a mutation in the BCKDHB gene.

This iPSC line shows a normal karyotype and can differentiate into all three germ layer lineages, indicating its potential for research and therapeutic applications in treating MSUD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An induced pluripotent stem cell line (SDQLCHi033-A) derived from a patient with maple syrup urine disease type Ib carrying a homozygous mutation in BCKDHB gene. Wang, B., Liu, C., Zhang, H., et al.[2021]

Transplanting VLA4+ neural stem and precursor cells (NPCs) into a mouse model of neuronopathic Gaucher disease (nGD) led to significant improvements in sensorimotor function and increased lifespan, demonstrating the potential efficacy of this treatment approach.

The VLA4+NPCs not only engrafted successfully in the brain but also reduced neuroinflammation and neurodegeneration, while enhancing GCase activity and decreasing harmful substrate levels, suggesting a multifaceted mechanism of action that supports neuronal health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous infusion of iPSC-derived neural precursor cells increases acid β-glucosidase function in the brain and lessens the neuronopathic phenotype in a mouse model of Gaucher disease. Peng, Y., Liou, B., Inskeep, V., et al.[2023]

Citations

1. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1465324915000705

Preclinical characterization of DUOC-01, a cell therapy ... DUOC-01 has potential as an adjunctive cell therapy to myeloablative CB transplant for treatment of inherited metabolic diseases. Introduction. Allogeneic ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02254863

NCT02254863 | UCB Transplant of Inherited Metabolic ... This study will evaluate the safety of a potential new treatment for patients with certain IMDs known to benefit from HSCT using allogeneic UCB donor cells.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9446943/

Abstract 15 Safety of DUOC-01, Intrathecal Cord Blood- ... DUOC-01 is a CB-derived product intended to accelerate donor cell delivery to the brain of children with IMDs undergoing CBT.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/25770677/

Preclinical characterization of DUOC-01, a cell therapy ... DUOC-01 has potential as an adjunctive cell therapy to myeloablative CB transplant for treatment of inherited metabolic diseases.

5. withpower.com withpower.com/trial/phase-1-brain-diseases-8-2014-889d4

Stem Cell Therapy for Inherited Metabolic Brain Diseases The DUOC-01 medical study, being run by Joanne Kurtzberg, MD, is evaluating whether DUOC-01 will have tolerable side effects & efficacy for patients with ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02254863

NCT02254863 | UCB Transplant of Inherited Metabolic ... This study will evaluate the safety of a potential new treatment for patients with certain IMDs known to benefit from HSCT using allogeneic UCB donor cells.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4843803/

Preclinical characterization of DUOC-01, a cell therapy ... Conclusions. DUOC-01 has potential as an adjunctive cell therapy to myeloablative CB transplant for treatment of inherited metabolic diseases.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02254863?term=AREA%5BConditionSearch%5D(Krabbe%20Disease)%20AND%20AREA%5BOverallStatus%5D(RECRUITING%20OR%20NOT_YET_RECRUITING)%20AND%20AREA%5BPhase%5D(PHASE1%20OR%20PHASE2%20OR%20PHASE3)&rank=1

UCB Transplant of Inherited Metabolic Diseases with ... This study will evaluate the safety of a potential new treatment for patients with certain IMDs known to benefit from HSCT using allogeneic UCB donor cells.