Huntington's disease
About
The pathogenic gene is clear-the CAG trinucleotide of the HTT gene on chromosome 4 is amplified repeatedly (normal <27 times, pathogenic>36 times), and the translation produces a mutant Huntington protein (mHTT) containing an abnormally extended polyglutamine bundle. mHTT forms inclusion bodies in the nucleus through acquired toxic functions, interfering with transcriptional regulation, mitochondrial function, and protein homeostasis. Core dilemmas: ①mHTT has both the dual effects of gain of toxicity and loss of function of wild-type HTT;② The 2021 Roche tominersen Phase III trial was terminated due to unsatisfactory efficacy;③ The disease began to undergo neurodegeneration 15-20 years before symptoms appear, and the treatment window is extremely narrow.
Features & Symptoms
- autosomal dominant inheritance
- Involuntary dance movements
- Cognitive decline and mental disorders
- Gradually lose the ability to live
Treatment Options
| Treatment | Description | Stage | Price Range |
|---|---|---|---|
| HTT-lowering allele-selective ASO/RNAi gene therapy | New generation strategy: Silence only mutant HTT alleles and retain the normal function of wild-type HTT. Wave Life Sciences 'WVE-003 was shown to reduce mHTT levels in cerebrospinal fluid in the 2024 Phase I/II trial. | Phase I/II | $350K - $800K/疗程 |
| CRISPR gene editing (CAG repeat excision) | CRISPR-Cas9 technology is used to accurately remove CAG repeat amplification fragments in the HTT gene to fundamentally correct pathogenic mutations. Multiple research teams have demonstrated effectiveness in HD mouse models and iPSC-derived neurons. | 临床前/Phase I | $600K - $1.5M/疗程 |
| Comprehensive neuroprotection + deep brain stimulation (DBS) protocol | Comprehensive symptomatic management for patients with advanced HD: DBS targeting medial globus pallidus reduces severe choreo-like movements; dopamine modulators control involuntary movements; high-intensity exercise training and cognitive rehabilitation maintain residual functions. | 临床应用 | $100K - $300K/年 |
Prognosis
Death 10-20 years after onset
Additional Notes
Notes: Genetic testing recommendations: Those with a family history should be tested for the number of CAG repeats in the HTT gene. CAG>36 can be diagnosed, and CAG>60 usually shows as adolescent type; Pre-symptomatic intervention: Patients with CAG repeats 40-50 can participate in clinical trials 5-10 years before symptoms, which is a key window for intervention; Exercise and cognitive rehabilitation: Regular aerobic exercise can delay the decline of motor function, and cognitive training can help maintain executive function; Mental symptom management: Depression, anxiety and suicidal tendencies are high in HD patients and require regular psychiatric assessments; genetic counseling: Patients 'children have a 50% genetic risk, so genetic counseling and PGT-M (pre-implantation genetic testing) are recommended before childbirth.; Exclusive service commitment: The platform will allocate a dedicated medical team to each patient to assist in dismantling and properly deploying the following precautions throughout the process. When cross-state and cross-border diagnosis and treatment projects or drugs are involved, the platform will make overall arrangements for the entire docking; for disabled and semi-disabled patient groups, the platform will provide rush-free alternative solutions (including remote consultation, door-to-door sampling, direct drug delivery in the cold chain, etc.), to ensure that patients can get the same high-quality diagnosis and treatment resources without having to travel in person.; Study phase: Phase II clinical. Prognosis: Death 10-20 years after onset.
Frequently Asked Questions
What is Huntington's disease?
The pathogenic gene is clear-the CAG trinucleotide of the HTT gene on chromosome 4 is amplified repeatedly (normal <27 times, pathogenic>36 times), and the translation produces a mutant Huntington protein (mHTT) containing an abnormally extended polyglutamine bundle. mHTT forms inclusion bodies in the nucleus through acquired toxic functions, interfering with transcriptional regulation, mitochondrial function, and protein homeostasis. Core dilemmas: ①mHTT has both the dual effects of gain of toxicity and loss of function of wild-type HTT;② The 2021 Roche tominersen Phase III trial was terminated due to unsatisfactory efficacy;③ The disease began to undergo neurodegeneration 15-20 years before symptoms appear, and the treatment window is extremely narrow.
What are the symptoms of Huntington's disease?
autosomal dominant inheritance,Involuntary dance movements,Cognitive decline and mental disorders,Gradually lose the ability to live
How is Huntington's disease treated?
HTT-lowering allele-selective ASO/RNAi gene therapy: New generation strategy: Silence only mutant HTT alleles and retain the normal function of wild-type HTT. Wave Life Sciences 'WVE-003 was shown to reduce mHTT levels in cerebrospinal fluid in the 2024 Phase I/II trial.; CRISPR gene editing (CAG repeat excision): CRISPR-Cas9 technology is used to accurately remove CAG repeat amplification fragments in the HTT gene to fundamentally correct pathogenic mutations. Multiple research teams have demonstrated effectiveness in HD mouse models and iPSC-derived neurons.; Comprehensive neuroprotection + deep brain stimulation (DBS) protocol: Comprehensive symptomatic management for patients with advanced HD: DBS targeting medial globus pallidus reduces severe choreo-like movements; dopamine modulators control involuntary movements; high-intensity exercise training and cognitive rehabilitation maintain residual functions.
What is the prognosis for Huntington's disease?
Death 10-20 years after onset