Spinocerebellar ataxia (SCA), the main type of hereditary ataxia, is a rare disease whose pathogenesis has not been fully elucidated. There is currently no effective treatment that completely stops the progression of the disease, and it is mainly symptomatic and supportive. Taltirelin, a TRH analogue that was marketed in Japan in 2000, can effectively improve the symptoms of dyskinesia in patients with SCA.
About Spinocerebellar Ataxia (SCA)
There is such a group of patients who stumble and stumble every day and even end up in a wheelchair, known as "penguin disease", a rare disease called spinocerebellar ataxia (SCA).
Spinocerebellar ataxia, a group of genetic diseases of the nervous system caused by genetic mutations in the cerebellum, brainstem, and spinal cord, with progressive motor coordination function and balance disorders as the main clinical manifestations, also known as autosomal dominant cerebellar ataxia. Moreover, the heritability of SCA is very high, and according to epidemiological surveys, "its prevalence may be between 1-5/100,000".
According to different pathogenic genes, SCA is divided into 43 subtypes, SCA3 is the most common subtype, in China SCA3 accounts for 51.1%-72.5% of all autosomal dominant SCA. The disease is usually asymptomatic at the onset of the disease, is not typical, and usually after 10 to 15 years the patient loses the ability to walk. Not only does it bring long-term physical and mental torture to the patients, but it also makes the whole family miserable.
Although SCA can currently be accurately diagnosed through genetic testing, it is still a problem in treatment. But in 2000, a drug, tertimorelin, was marketed in Japan, which could effectively improve the symptoms of movement disorders in SCA patients.
About him Tatirelin
Tatirridelin, a synthetic thyrotropin-releasing hormone (TRH) analogue developed by the Japanese company Tanabe Seiyaku and first launched in Japan in September 2000, is suitable for improving ataxia in patients with spinocerebellar degeneration, and its trade name is Ceredist.
1. TRH analogue
Thyrotropin-releasing hormone (TRH) is a pituitary hormone in the hypothalamus. Its main function is to maintain the release of thyroid hormones and to regulate the release of other pituitary hormones. Moreover, studies have found that TRH is also present in non-neural tissues, such as the skin, gastrointestinal tract, etc., so the role of TRH is very extensive.
Because the plasma half-life of TRH is very short, only 4 to 5 minutes, which greatly limits the clinical role of TRH, so TRH analogues appear.
2. Clinical evaluation of tatiridelin Tatirelin
Thyrotropin-releasing hormone (TRH), present in the brain, co-localizes with other neurotransmitters or temperants to function as neurotransmitters or neuromodulators. Therefore, TRH and its analogues have a neuroprotective effect.
According to studies, dopamine in the brain is involved in the regulation of the motor system, while one of the main symptoms of spinocerebellar ataxia (SCA) is progressive motor coordination decline. TRH and its analogues have been shown to alter the metabolism of acetylcholinesterase and dopamine, thereby activating the dopamine system.
Tatirrelline is the first synthesized effective oral THR analogue, which has an excitatory effect on the central nervous system 100 times that of TRH, a duration of action 8 times longer than TRH, and is also more stable in vivo than TRH. Clinical studies have shown that tatatreline is a well-tolerated and safe central nervous system drug.
In a randomized, double-blind, placebo-controlled Phase III clinical trial, 427 patients with spinocerebellar degeneration were randomized with tertimorelin and placebo, and after 28 weeks, the overall improvement rate of the tatirelin group was significantly better than that in the placebo group (P
In 2009, Zenichiro Kato et al. again found in an 18-year-old male patient with type III spinal muscular atrophy that their muscle strength was significantly improved after oral administration of tereparine hydrate.
3. Use, adverse reactions and contraindications of tatitrelin Tatirelin
The drug is taken as an oral tablet, adults take 5 mg twice a day after breakfast and dinner. It is important to note that this drug is contraindicated in people with impaired renal function. In addition, the adverse reactions of the drug are mainly digestive system problems, including nausea, vomiting and stomach discomfort, etc., if patients taking this drug have similar problems should consult a doctor as soon as possible, do not continue to take the drug on their own. Since the drug is a prescription drug in Japan, it is not currently available in Japan.
Conclusion and Outlook
About him tirring, the price developed by Mitsubishi Tanabe is about 970 yen, for many patients, the long-term economic burden is still relatively heavy, however, patients can get the overseas version of the preferential price of ta tirin through regular overseas service agencies (such as: medical companion travel). In addition, there are also generic drugs of Terrelin to choose from.
At present, the "Raelin" drug is also under continuous research and development, and Rovatirelin has also been studied to have a significant effect on patients with spinocerebellar dysregulation. Most of the SCA patients are young and middle-aged, which has brought a great blow to their life and career, and because the disease is a rare disease, it has certain difficulties in diagnosis and treatment. Although it is not yet possible to fully treat patients with SCA, I believe that there will be more and better drugs in the future that can treat patients with spinocerebellar dysregulation.