Canavan disease (CD) is a rare and fatal genetic disorder that affects the white matter of the brain. The disease can be a devastating condition that primarily affects infants, causing severe developmental delays and progressive neurological damage. For decades there has been little hope for combating the disease. However, in recent years new data and new research have cast light on promising novel therapies. In this article, we sit down with Myrtelle to explore a potential treatment option for Canavan disease.
Since the early 20th century, researchers have been searching for new and innovative ways to treat neurological disorders and new information on the disease has been constantly emerging. Sadly, treatments have been scarce, and patients have been left with few options to manage their disease. However, in recent years, gene therapy companies, such as Myrtelle Inc, have been tapping into potential new treatment options by combining decades of research and innovative new medical technology.
Myrtelle is a biotechnology company specializing in white matter diseases, and disorders in which the production of myelin is affected. They have been committed to confronting the problems these diseases pose and developing what the company hopes will be effective solutions. In particular, one clinical trial they are conducting had exciting evidence pointing to a potential new therapy for Canavan disease, a rare pediatric disorder that results from mutation of the ASPA gene. The treatment involves developing a novel adeno-associated virus (AAV) vector that delivers a corrective gene to the cells that make myelin in the brain called oligodendrocytes. The hope is that this novel therapy could lower N-acetyl aspartate (a neurochemical in the brain that accumulates in CD patients) and possibly halt or even reverse white matter deterioration, brain atrophy, and functional decline these patients experience.,
What are oligodendrocytes?
Oligodendrocytes are a type of glial cell in the central nervous system (CNS) that play a crucial role in the formation and maintenance of myelin, the fatty substance that surrounds and insulates nerve fibres, enabling them to conduct electrical impulses efficiently. Without sufficient myelin, the CNS cannot function properly, leading to a range of neurological disorders, such as multiple sclerosis (MS) and other white matter disorders (leukodystrophies), which include Canavan Disease.
Myrtelle’s oligodendrocyte-specific AAV aims to increase the production of myelin by selectively targeting oligodendrocytes in the central nervous system. AAV is a type of non-pathogenic (non-disease-causing) virus that can be engineered to deliver therapeutic genes to specific cells in the body, and in this case, Myrtelle’s AAV carries a gene called ASPA that stimulates the production of myelin.
The AAV vector is designed to specifically target oligodendrocytes. This helps limit expression to oligodendrocytes, reducing the risk of off-target effects.
The recombinant adeno-associated virus therapy objective and strategy
Myrtelle’s clinical trial for the rAAV-Olig001-ASPA gene therapy has a clear set of goals and objectives, developed in connection with leading physicians, scientists and regulatory authorities, that are designed to test its safety and effectiveness. The primary objective of the clinical trial is to evaluate the safety and tolerability of the therapy, which involves closely monitoring patients for any immediate side effects or complications following the administration of gene therapy. This is an essential step in ensuring that the treatment is safe for patients and does not cause any significant harm or adverse reactions.
In addition to the primary objective of evaluating the safety and tolerability of the therapy, the clinical trial also has several secondary clinical objectives. These objectives include measuring the pharmacodynamic effects of gene therapy and assessing its efficacy in improving patient outcomes. To achieve these objectives, a range of specialized assessments will be conducted, including the Gross Motor Function Measure (GMFM), Mullen Scales of Early Learning (MSEL), and the Comprehensive Neurological Examination (CNE), which includes videotaping, seizure inventory, and EEG. By closely monitoring these secondary objectives, researchers hope to gain a better understanding of the potential effectiveness of the rAAV-Olig001-ASPA gene therapy in stopping or even reversing the functional decline, brain atrophy, white matter deterioration, and NAA (N-Acetylaspartate) accumulation, which are all key factors in the pathogenesis of Canavan disease.
The development of any new medical treatment is a complex and multi-faceted process that requires careful planning, meticulous research, and rigorous testing to ensure its safety and effectiveness. In the case of Myrtelle’s rAAV-Olig001-ASPA gene therapy, this is especially true given the complexity of Canavan disease and the challenges involved in developing effective treatments for neurological disorders.
The success of this therapy depends on a variety of factors, including the quality of the research that goes into its development, the expertise and skill of the researchers and clinicians involved in its testing and administration, the production of top-quality gene therapy drug material, and the careful monitoring of patients to ensure that the therapy is safe and effective.
To achieve these goals, Myrtelle has taken a methodical approach to the development of its candidate gene therapy. This includes conducting extensive preclinical studies to assess safety and efficacy, designing carefully controlled clinical trials to test the therapy in humans, and collaborating with leading researchers and clinicians to ensure that the therapy is developed and administered in the most effective way possible.
How does the therapy work?
Identifying potential candidates
To participate in the clinical trial for ’Myrtelle’s rAAV-Olig001-ASPA gene therapy, patients must meet a specific set of eligibility criteria. Firstly, they must have a confirmed genetic diagnosis of Canavan disease and must be within the age range specified in the protocol. These criteria are carefully designed to identify patients who are reasonably likely to benefit from the treatment and to minimize any potential risks or complications associated with the therapy. By carefully selecting eligible patients, the clinical trial aims to yield meaningful results that can ultimately lead to the development of a safe and effective cure for Canavan disease.
The rAAV-Olig001-ASPA gene therapy is administered through a single dose, one-time administration into the two sites of the brain, known as lateral ventricles, using a method called intracerebroventricular (ICV) route of administration. This route of administration is particularly effective as it directly targets the oligodendrocytes in the brain – the cells most involved in the pathogenesis of CD – and delivers the functional copy of the ASPA gene precisely where it is needed. This unique approach to gene therapy delivery has the potential to revolutionize the treatment of Canavan disease and offer a promising new avenue for patients suffering from this debilitating disease.
Post-therapy responsibilities for families and caregivers
Following the administration of Myrtelle’s rAAV-Olig001-ASPA gene therapy, patients are carefully monitored to ensure the safety and effectiveness of the treatment. For months after the therapy is administered, patients are closely monitored at the treatment site to assess for any immediate side effects or complications. Subsequently, patients are followed for a total of five years post-treatment, with regular visits to the clinical site at various intervals during this period. Specifically, patients will have follow-up visits at 1, 3, 6, and 12 months post-treatment, and then once every 12 months thereafter.
During these visits, a comprehensive range of assessments will be conducted as per the study protocol to monitor the patient’s overall health and neurological function. These assessments will include physical examinations, neurological testing, MRI and spectroscopy, laboratory tests, and other specialized assessments to evaluate specific aspects of the patient’s health. By closely monitoring patients over this five-year period, researchers can evaluate the long-term safety and efficacy of the rAAV-Olig001-ASPA gene therapy and gain a better understanding of its potential to revolutionize the treatment of Canavan disease.
Hope on the horizon
The development of Myrtelle’s oligodendrocyte-specific gene therapy represents a potentially significant step forward in the field of gene therapy and holds immense promise for the treatment of neurological disorders. The selective targeting of oligodendrocytes represents a potentially safer and more effective approach to increasing myelin production and preventing or reversing neurological damage in patients with Canavan disease and other similar disorders.
While the oligodendrocyte-specific AAV is still in its early stages of development, the potential benefits it may offer are enormous. The current lack of effective treatments for neurological disorders highlights the urgent need for new and innovative approaches to improve patient outcomes. With further research and clinical trials, Myrtelle’s AAV could potentially revolutionise the treatment of multiple neurological disorders and bring much-needed relief to people around the world who suffer from these devastating conditions.
Myrtelle’s commitment to advancing the field of gene therapy and developing new treatments for neurological disorders is inspiring. The hope and potential benefits that this research may bring to patients and their families are significant, and we eagerly await the results of the clinical trials and the potential impact they could have on the future of neurological care.
Helen Baumeister, a psychology graduate from the University of Hertfordshire, has a keen interest in the fields of mental health, wellness, and lifestyle.