What side effects are associated with this type of intervention?

Common treatments for Multiple System Atrophy (MSA) include medications to manage symptoms such as autonomic dysfunction, motor symptoms, and sleep disturbances. These treatments can have side effects such as orthostatic hypotension, gastrointestinal issues, and sedation. Gene therapy approaches like AAV2-GDNF, which aim to deliver neurotrophic factors to support neuronal survival, are still under investigation. Potential side effects of gene therapy can include immune reactions, off-target effects, and the risk of infection at the injection site. As these therapies are experimental, ongoing trials are crucial to fully understand their safety profiles.

What prior FDA approvals exist?

As of now, there are no specific FDA-approved treatments for Multiple System Atrophy (MSA) that are similar to the AAV2-GDNF gene therapy, which aims to deliver glial cell line-derived neurotrophic factor (GDNF) to support neuronal survival and function. Current treatment approaches for MSA are primarily symptomatic, focusing on managing symptoms such as motor dysfunction, autonomic failure, and other non-motor symptoms. Research is ongoing to find disease-modifying therapies, including gene therapies like AAV2-GDNF, which hold promise for future treatment options.

What other types of research exist?

Promising novel alternatives to AAV2-GDNF for Multiple System Atrophy patients include: 1) Antisense oligonucleotide (ASO) therapies, which have shown potential in other neurodegenerative diseases like ALS and Huntington's disease. 2) Neurotrophic factor-secreting stem cell therapies, such as mesenchymal stem cells (MSCs) engineered to secrete neurotrophic factors. 3) Small molecule neuroprotective agents like sodium phenylbutyrate/taurursodiol, which have demonstrated efficacy in ALS. These alternatives are in various stages of clinical development and may offer new avenues for treatment in 2024.

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Gene Therapy

GDNF Gene Therapy for Multiple System Atrophy

Phase 1

Recruiting

Research Sponsored by Brain Neurotherapy Bio, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Stable anti-parkinsonian medication regimen

Male and female 35-75 years of age (inclusive)

Must not have

History of cancer or poorly controlled medical conditions that would increase surgical risk

Presence of idiopathic Parkinson's disease (PD) or any PD-related mutation or other neurological diseases

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 3 years

Summary

This trial is testing a new gene therapy for people with Multiple System Atrophy (MSA). The therapy uses a harmless virus to deliver a gene into the brain, which then produces a protein that helps protect brain cells. The goal is to see if this treatment is safe and if it can help slow down the progression of MSA.

Who is the study for?

Adults aged 35-75 with Multiple System Atrophy (MSA) and parkinsonian symptoms, who can walk independently or with help. They must be diagnosed within the last 4 years, have a life expectancy over 3 years, and be on stable medication for MSA. Excluded are those with Parkinson's disease, dementia, psychosis, substance abuse issues, prior brain surgery or cancer.

What is being tested?

This study tests AAV2-GDNF gene therapy versus a sham surgery to see if it's safe and effective for treating MSA. Participants will randomly receive either the real treatment directly into their brains or a placebo procedure without knowing which one they got.

What are the potential side effects?

Potential side effects of AAV2-GDNF gene therapy may include reactions at the injection site in the brain, headache, nausea or other neurological changes due to its novel nature; however specific risks will be monitored closely given this is an early-phase trial.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My Parkinson's medication dose has been stable.

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I am between 35 and 75 years old.

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I was diagnosed with MSA-Parkinsonian type after turning 30, and my symptoms have been getting worse.

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I can walk 25 feet with or without help.

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I was diagnosed with MSA after 30, showing mainly Parkinson-like symptoms.

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I am between 35 and 75 years old.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a history of cancer or medical conditions that make surgery risky.

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I have Parkinson's disease or a related genetic condition.

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I have had brain surgery or have abnormalities in brain scans.

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I cannot lay flat in an MRI or am allergic to gadolinium.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 3 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~3 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 3 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

The incidence of Treatment-Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) assessed clinically by physical and neurological examinations

Secondary study objectives

Change in striatal dopamine transporter binding as measured by [123-I] Ioflupane

Change in the quality of life as measured by Multiple System Atrophy Quality of Life (MSA-QoL)

MSA symptoms/signs as assessed by the Unified Multiple System Atrophy Rating Scale (UMSARS)

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: Active TreatmentExperimental Treatment1 Intervention

Group II: Placebo SurgeryPlacebo Group1 Intervention

0 / 10Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Multiple System Atrophy (MSA) treatments primarily aim to manage symptoms and slow disease progression. AAV2-GDNF gene therapy, which delivers Glial cell line-Derived Neurotrophic Factor (GDNF) to the putamen, supports neuronal survival and function by promoting the growth and maintenance of dopaminergic neurons. This is crucial for MSA patients as it targets the underlying neurodegeneration, potentially improving motor function and slowing disease progression. Other treatments, such as levodopa, aim to alleviate parkinsonian symptoms by replenishing dopamine levels, but they do not address the neurodegenerative process directly. The emphasis on neuroprotective strategies like GDNF gene therapy represents a promising approach to modifying the disease course in MSA.