About Spinocerebellar Ataxia (SCA)
About Spinocerebellar Ataxia (SCA)
Treatment for Spinocerebellar Ataxia currently lacks effective methods, and management mainly focuses on alleviating symptoms and improving quality of life based on clinical presentations such as slow movements, tremors, lack of muscle tone, stiffness in limbs, muscle spasms, and depression.
Spinocerebellar Ataxia (SCA) is a rare disease that encompasses a group of disorders with similar symptoms, which may include symptoms of spinal cord and cerebellar lesions. Among these, Spinocerebellar Ataxia (SCA) is a dominantly inherited neurodegenerative disease. To date, more than 48 different SCA subtypes have been identified, primarily affecting the cerebellum (especially Purkinje cells), brainstem, and other non-spinocerebellar tissues. The cause is an abnormal sequence in specific genes, with a hereditary rate of 50%. The disease usually manifests in adulthood (between the ages of 30 and 50) and progressively worsens over several decades. Some patients may survive nearly 30 years after symptoms appear. Additionally, onset can occur in adolescence or after the age of 70 due to differences in the size of the disease-causing DNA repeat.
One of the most common subtypes is SCA3 (Spinocerebellar ataxia type 3), also known as Machado-Joseph disease (MJD). SCA3 is an inherited, fatal neurodegenerative disease attributed to abnormal accumulation of polyglutamine (polyQ) generated by the mutated ataxin-3 gene (ATXN3). Toxic fragments produced by the mutated ATXN3 can induce neuronal death, resulting in muscular incoordination in affected individuals.
The disease primarily affects the cerebellum, spinal cord, and brainstem, leading to coordination disorders. Typically, patients will need wheelchair assistance 10 to 15 years after symptom onset. The age of onset and severity of symptoms in SCA3 vary greatly among patients, even within the same family. This variability is due to the type of disease-causing genetic defect in SCA3, which involves a DNA triplet repeat expansion. The repeat expansion in SCA3 varies in size among affected individuals. Generally, the longer the repeat, the stronger the effect of the mutation, resulting in earlier disease onset. The greater the expansion, the more severe the disease.
Globally, approximately 3 out of 100,000 individuals are affected by spinocerebellar ataxia, with an estimated 15,000 to 20,000 cases reported in the United States alone. As of August 2023, the Taiwan Ministry of Health and Welfare has reported 1,534 cases. To date, there is no effective treatment available, underscoring the ongoing need for active exploration and research by scientists.
Background of Spinocerebellar Ataxia
Lack of Effective Treatment: Currently, there are no effective treatments available for cerebellar atrophy. Symptomatic treatment is provided based on clinical manifestations such as delayed movements, tremors, lack of muscle tone, stiffness, muscle spasms, and depression, aiming to improve the quality of life. Future therapies for SCA may include gene therapy, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) gene editing, stem cell therapy, antisense oligonucleotides (ASO), and drug formulations.
Loss of Coordination: Patients are usually diagnosed with Spinocerebellar Ataxia after experiencing the following symptoms, which are confirmed by a physician: poor coordination, slurred speech, difficulty eating and swallowing, limited fine motor skills, difficulty walking, abnormal gait, abnormal eye movements, tremors, and heart problems. The range of symptoms in SCA3 is typically broader than in other forms of ataxia.
Portrayal in Films and TV Shows: The Japanese classic TV drama “1 Litre of Tears” (リットルの涙) was adapted from a script written by a cerebellar atrophy patient. Diagnosed with the disease at the age of 15, the author found solace in diary writing to encourage herself to persevere in life. With the support of family and friends, she bravely lived until the age of 25 before passing away. The final episode of the drama achieved a remarkable 20% viewership rating in Japan, sparking significant public response. In 2011, Taiwan released a film titled “Take Me to the Moon,” depicting the true story of a husband pushing his wheelchair-bound wife, who suffered from cerebellar atrophy, to circumnavigate the island on foot. Through these cinematic works, we gain deeper insight into the challenges faced by individuals with cerebellar atrophy and their families, while also witnessing their courageous spirit and resilience in life.
Diagnosis: Cerebellar atrophy is often misdiagnosed as other neurodegenerative diseases such as multiple sclerosis. A more widely known example would be amyotrophic lateral sclerosis (ALS), which is a central nervous system disorder involving the degeneration of motor neurons. Although initial symptoms may appear similar, ALS and cerebellar atrophy occur in different locations within the brain and are entirely distinct diseases. Physicians assess patients for symptoms of cerebellar and spinal cord neurodegeneration through neurological examinations. Additional evaluation includes family history assessment, magnetic resonance imaging (MRI), and genetic testing to confirm the diagnosis of cerebellar atrophy.
Current Treatment for Spinocerebellar Ataxia
Spinocerebellar Ataxia currently lacks effective treatment, and management focuses on symptom relief, improving quality of life, and delaying disease progression. Possible treatment options include:
Medication: Symptom control through medication is a common approach. For instance, antispasmodic drugs can alleviate muscle spasms and tremors. Other medications may be prescribed to manage conditions such as insomnia or depression.
Physical Therapy: Physical therapy aims to enhance muscle strength, coordination, and daily functioning, thus improving quality of life. Exercises like muscle training, balance training, and walking exercises are employed to achieve this.
Speech Therapy: Speech therapists assist patients in overcoming speech and communication difficulties, enhancing their speaking and communication skills.
Supportive Care: Emotional support and caregiving are essential aspects of managing cerebellar atrophy. Providing support to both patients and their families helps them cope with the impact of the disease and offers necessary social and psychological support.
Early diagnosis and collaboration with healthcare professionals for comprehensive treatment can help patients better manage symptoms, improve their quality of life, delay disease progression, and alleviate the burden on caregivers.
The medications currently under investigation in clinical trials include:
Due to the limited efficacy of current medications and their limited impact on patient survival and quality of life, many researchers are seeking more effective drugs and treatment methods.
Stemchymal®
Stemchymal® is an off-the-shelf stem cell product developed by Taiwan’s Steminent Biotherapeutics Inc. for the treatment of PolyQ spinocerebellar ataxias (SCAs).
It has completed Phase I/II clinical trials and Phase II clinical trials in Taiwan.
Reference: http://www.steminent.com/stemchymalpolyqsca/
Troriluzole Injection
Troriluzole is a prodrug of Riluzole, currently used in the treatment of ALS. It is a medication that acts by blocking glutamate, an excitatory amino acid believed to be associated with excitotoxicity and neuronal degeneration.
Troriluzole is a small molecule drug discovered through Biohaven’s glutamate modulation platform. Unfortunately, the Phase III clinical trial results in 2022 (NCT03701399) for the treatment of SCA3 did not meet its primary endpoint of statistical significance. The drug is now being redirected towards clinical trials for obsessive-compulsive disorder.
Additionally, clinical trial results published in 2022 for Riluzole showed no improvement in clinical or radiological outcomes in patients with SCA type 2.
Rovatirelin
Teshirogi, a derivative of thyrotropin-releasing hormone (TRH) developed by Kissei Pharmaceutical in Japan, acts by binding to TRH receptors distributed in the central nervous system. It promotes the release of monoamine neurotransmitters such as acetylcholine and dopamine to activate the nervous system, aiming to improve ataxia in patients with spinocerebellar degeneration.
The company temporarily withdrew its application for market approval in 2023 and discussed the possibility of additional clinical trials with the Pharmaceuticals and Medical Devices Agency (PMDA). As of 2024, there have been no recent updates on this matter.
TSCA-001
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TSCA-001 is a drug under development by Everfront Biotech for the treatment of SCA3. It has completed preclinical efficacy testing in animals at this stage.
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The function of TSCA-001 is to regulate the early metabolism pathway of kynurenine, reducing the expression of tryptophan 2,3-dioxygenase (TDO2) and thereby lowering the production of downstream neurotoxic metabolite quinolinic acid (QA). Additionally, by controlling TDO2, TSCA-001 also reduces the levels of active calpain, an important enzyme involved in the degradation of mutant ATXN3 protein, thereby decreasing the generation of toxic fragments and related neurotoxicity.
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The active small molecule drug TSCA-001 has high penetrability and can cross the blood-brain barrier. Through formulation design, it can achieve higher drug concentrations in targeted therapeutic organs such as the brain (including the cerebrum and cerebellum).
More information>>TSCA-001
Care and Precautions for Patients with Spinocerebellar Ataxia (SCA)
Psychological Support
Cerebellar atrophy is a neurological disorder that leads to the degeneration and impairment of cerebellar tissue. Patients may experience symptoms such as muscle atrophy, motor dysfunction, and speech and cognitive impairment. Family members and caregivers need to understand these symptoms and how to address the patient’s care needs.
Dietary Considerations
Due to neurological degeneration in the brain, patients with cerebellar atrophy may experience difficulty swallowing and delayed swallowing. Therefore, it is advisable to avoid overly dry or thick foods and prioritize easily flowing foods. Additionally, increasing intake of anthocyanins, folic acid, and reducing consumption of trans fatty acids can help reduce the risk of brain inflammation.
Regular Physiotherapy Sessions
Despite the impact of cerebellar atrophy on patients’ motor abilities, regular exercise and physiotherapy remain crucial. Adequate exercise can help improve muscle strength and coordination, alleviate muscle stiffness and pain, and maintain joint flexibility. Family members and caregivers should encourage patients to participate in appropriate exercise and physiotherapy activities.
A 33-year-old young man in Hong Kong maintains his physical abilities by doing exercises at home, focusing on his chest, back, and arms. He also rides a stationary bike for an hour each day and can lift 4 kg dumbbells. This approach can serve as a reference for others with similar conditions, as long as they keep the intensity appropriate and avoid overexertion that could lead to injury. (Source: Newspaper)
Regular Medical Checkups and Follow-ups
For individuals with cerebellar atrophy, regular medical checkups and treatments are crucial. They help monitor the progression of the disease, detect and address any underlying health issues early on, and ensure patients receive appropriate medication and support.
Safe Environment
Individuals with cerebellar atrophy may experience mobility issues or poor coordination. It’s essential for family members and caregivers to ensure a safe environment at home to prevent accidental injuries. Additionally, providing a comfortable living environment, including appropriate temperature, adequate lighting, safe walking spaces, and comfortable bedding, can help improve the patient’s quality of life.
