Huntington's disease (HD) is also known as "hereditary chorea" and "chronic progressive chorea" . Huntington's disease is a hereditary neurodegenerative disease caused by an autosomal dominant mutation that causes the gradual depletion (degeneration) of nerve cells in the brain. Huntington's disease has a wide range of effects on a person's function and ability, often leading to motor, thinking (cognitive) and mental disorders.
Huntington's disease is a dominant inherited neurodegenerative disease, which is clinically diagnosed on the basis of positive family history, typical dancing-like motor symptoms, mental disorders and progressive dementia, and positive results of genetic testing.
5.1 Symptom-Based Diagnosis
- Motor symptoms: reaction, muscle strength, muscle tension, coordination, balance.
- Sensory symptoms: touch, vision and eye movement, hearing.
- Psychiatric symptoms: mental state and mood.
Standardized examination: the unified HD score scale (UHDRS) is currently the most commonly used clinical and research tool for HD assessment. The scale includes components of movement, cognition, behavior, emotion and function.
5.2 Electroencephalogram (EEG)
Brain imaging tests are used to assess the structure or function of the brain. The main techniques include magnetic resonance imaging (MRI) or computed tomography (CT).
Typical imaging features: bilateral caudate nucleus atrophy. Magnetic resonance imaging (MRI) has shown extensive brain atrophy in HD studies, most notably in the striatum .
SPECT examination showed a significant decrease in blood flow in the caudate nucleus and the lenticular nucleus, and decreased blood flow in the frontal and parietal lobe.
PET examination showed that the glucose metabolism in caudate nucleus decreased in patients with subclinical status, which can be used for super early diagnosis.
5.3 Genetic Testing
It is an important means of diagnosis. The number of repeated copies of CAG in Huntington's gene (TT15) was detected by PCR. Normal people had no more than 38 copies, and patients had more than 39 copies.
Genetic testing can be diagnostic or predictive. If the patient has typical characteristics of Huntington's disease, the most effective confirmatory diagnostic test is the cag-repeat test .
In symptomatic Huntington's disease, levodopa can aggravate choreography. Therefore, it can be used for early diagnosis, but the test has a certain false negative reaction.
Studies have shown that qEEG may also serve as a biomarker for HD to help monitor the efficacy of intervention studies .
In addition, inflammation may act as a biomarkers of Huntington's disease .
The latest study found that blood tests can detect the earliest changes caused by Huntington's disease, even before the scan can detect any signs in the brain.
The study of pathogenic molecules in cerebrospinal fluid (CSF) is also one of the ways to find biomarkers .
Like most neurodegenerative diseases, Huntington's disease lacks specific treatment methods, and symptomatic treatment is mainly used at present.
With proper medication, the symptoms of motor and mental disorders can be alleviated, and the quality of life of patients can be improved and complications can be prevented.
6.1 Medical Treatment
In mice model, the researchers found that a bile acid was effective in reducing damage to nerve cells in the brain. If future studies prove that bile acid therapy works in humans and can prevent the death of nerve cells in the brain at an early age, it may be possible to prevent Huntington's disease for life.
- Antidepressants: Celexa, Lexapro, Prozac, Sarafem and Zoloft. Side effects include nausea, diarrhea, lethargy, and low blood pressure.
- Antipsychotic drugs: Quetiapine and risperidone and olanzapine can inhibit the symptoms of emotional disorder or psychotic violence and agitation. The side effect is that these drugs may cause different motor disorders.
- Mood stabilizers: Depacon, Carbatrol, Epitol, Tegretol and lamotrigine.
In addition, Congo red can prevents the accumulation of abnormal proteins in the brain and prevents Huntington's disease. The findings provide new insights into the treatment of Huntington's disease, but further research is needed before the method can be used clinically.
6.2 Other Treatments
In addition to medical treatment, psychotherapy, language therapy, physical therapy and occupational therapy are also commonly used treatments, which can improve basic symptoms to some extent.
Psychotherapists can help patients deal with behavioral problems, develop strategies, and promote effective communication between family members.
A speech therapist can help you improve your ability to express yourself clearly or teach you how to use communication tools. Speech therapists can also help with eating and swallowing muscle problems.
Exercise properly and safely to increase strength, flexibility, balance and coordination.
Occupational therapists can help patients with Huntington's disease use assistive devices that improve their functioning.
Diet and Nutrition
It is often difficult for Huntington's chorea to maintain a healthy weight. In order to get enough nutrition, it may be necessary to have more than three meals a day or to use dietary supplements.
When dining, choose foods that are easy to eat. Use instruments designed for people with limited motor skills (cups with straws or water outlets).
The treatment of Huntington's disease by cell transplantation is still under exploration. Brain cell transplantation can alleviate Huntington's disease to some extent, but this method is controversial.
The method of RNAi can reduce the HD protein level of mice and effectively improve the related motor and neurological abnormalities caused by HD in mice.
6.3 Other Therapeutic Targets
Autophagy is the primary pathway leading to the clearance of aggregated proteins in Huntington's disease, and autophagy induction prevents HD-mediated neurotoxicity . mTOR inhibitors and rapamycin-induced autophagy speed up the removal of these toxic substrates. Mammalian cell, fly and zebrafish models provide a theoretical proof for the therapeutic relevance of Huntington's disease .
Mutant HTT (mHTT) will undergo a series of post-translational modifications, such as ubiquitination and phosphorylation  . Deubiquitinase Usp12 plays a non-catalytic autophagy and neuroprotective role in Huntington's chorea model .
IGF-1/Akt pathway plays a neuroprotective role in Huntington's chorea, and Akt phosphorylation of huntingtin is crucial for the neuroprotective role of IGF-1 .
Based on these findings, new therapeutic strategies can be developed.
In addition, a new CRISPR cas9-based gene editing method for Huntington's disease can inactivate HTT alleles associated with HD-related mutations without affecting normal alleles.
If safety is demonstrated in animal models and humans, it will have broad application prospects.
For more information, Huntington's disease organizations and some websites related to Huntington's disease can help you:
Huntington's Disease Society of America: https://hdsa.org/
The Huntington's Disease Youth Organization: https://en.hdyo.org/
Huntington's Disease Association: https://www.hda.org.uk/contact-us/branches-and-support-groups
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