by Leigh syndrome, also known as subacute necrotizing encephalomyelopathy, is a rare and progressive neurological disorder that affects the central nervous system. The condition primarily affects the brainstem and its associated structures and spinal cord, resulting in symptoms that typically manifest before the age of 2 years. Leigh syndrome causes degeneration of nerve cells and tissue in the areas of the brain that control respiration, movement, and other essential functions.
Causes and Genetics of Leigh Syndrome Treatment Industry
Leigh syndrome is nearly always genetic in origin and can be caused by mutations in any of over 75 different nuclear genes that code for respiratory chain subunits and assembly factors. These underlying genetic defects disrupt cellular ATP production and respiratory chain function, leading to neuronal injury and death in highly energy-dependent areas of the brain and spinal cord. Although Leigh syndrome can be inherited in both dominant and recessive patterns, the majority of cases are sporadic, meaning there is no identifiable family history. Genetic testing helps identify the specific mutation and provides information about prognosis and recurrence risk.
Clinical Presentation and Symptoms
The signs and symptoms of Leigh syndrome vary greatly depending on which areas of the central nervous system are affected. Common clinical features seen in infants and young children include lack of muscle control and loss of motor skills, breathing problems, feeding difficulties, vision problems, and delayed development. Other nonspecific symptoms may include lethargy, vomiting, seizures, and abnormal movements. As the disorder progresses, symptoms worsen and involve multiple systems as more areas of the brain are damaged over time.
Current Treatment Options and Therapies
Unfortunately, there is no cure for Leigh syndrome and management is primarily supportive and aims to minimize symptoms. Continuous respiratory support is often necessary in the form of tracheostomy and long-term ventilation support. Severe feeding difficulties may require gastrostomy tube placement for nutrition. Medications are used to control seizures and manage complications like spasticity, hypotonia, or weakness. Physical, occupational, and speech therapy can help improve motor skills and assist with activities of daily living.
Stem Cell Therapy as a New Treatment Approach
Given the limited effectiveness of current treatments, researchers have begun exploring the potential of various regenerative medicine approaches for Leigh syndrome. Stem cell therapy shows promising preliminary results as a novel way to replace damaged cells and recover function. A pioneering clinical trial in 2021 transplanted neuronal stem cells directly into the brain of a 15-month-old boy with Leigh syndrome. Following the procedure, his symptoms stabilized and there were improvements in motor skills, vision, and alertness that were sustained for more than 6 months.
Current Stem Cell Clinical Trials
Several new stem cell clinical trials are now underway globally to further evaluate safety and efficacy in Leigh syndrome patients. A Phase I trial is recruiting 10 participants ages 1-12 years in China to receive intrathecal stem cell injections. Another Phase I/II trial will enroll 10 subjects ages 2-18 years in Mexico, who will undergo direct brain injections of neuronal stem cells. Looking ahead, additional trials with larger sample sizes incorporating control groups are essential next steps. Stem cell therapy may hold potential as a disease-modifying treatment if continued positive results are seen across various clinical settings.
Gene Therapy as an Emerging Therapeutic Approach
Along with stem cell therapy, gene therapy also shows promise as a transformative treatment strategy for Leigh syndrome and other mitochondrial disorders. Early gene therapy studies aim to correct the underlying genetic defect and restore normal functioning through delivery of healthy gene variants. A Phase I/II clinical trial just launched in the UK will administer recombinant adeno-associated virus serotype 9 carrying NDUFS4, a complex I gene, directly into the brain. Preliminary animal research suggests gene correction preserves neurons and improves behaviors. Outcomes from this initial human trial will guide how gene therapy for specific Leigh syndrome mutations can be advanced.
while cure remains the long-term goal, regenerative strategies like stem cell and gene therapies have opened up new avenues for addressing Leigh syndrome that was not possible before. Early results indicate these approaches may provide lasting clinical benefit by compensating for mitochondrial dysfunction and neurodegeneration. Large, controlled trials are still required to fully validate safety and efficacy. Nonetheless, regenerative medicine shows exciting promise as the next frontier through which the devastating effects of this syndrome may potentially be modified or even reversed. With continued progress and collaboration globally, these innovative therapies have the capacity to transform treatment for patients and families affected by Leigh syndrome.
Note:
1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it
